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نشرة الممارس الصحي	نشرة معلومات المريض بالعربية	نشرة معلومات المريض بالانجليزية	صور الدواء	بيانات الدواء

رقم التسجيل

1405257385

سنة التسجيل

2025

الاسم التجاري

MenQuadfi

الاسم العلمي

MENINGOCOCCAL (SEROGROUP A) POLYSACCHARIDE,MENINGOCOCCAL (SEROGROUP C) POLYSACCHARIDE,MENINGOCOCCAL (SEROGROUP Y) POLYSACCHARIDE,MENINGOCOCCAL (SEROGROUP W135) POLYSACCHARIDE,TETANUS TOXOID

التركيز

10,10,10,10,55

وحدة التركيز

µg

طريقة الإستعمال

Intramuscular use

الشكل الصيدلاني

Solution for injection

الحجم

وحدة الحجم

حجم العبوة

انواع العبوات

Vial

طريقة الصرف

Prescription

حالة المراقبة

Uncontrolled

نوع الدواء

Biological

مدة الصلاحية بالأشهر

شروط التخزين

Store in a refrigerator (2°C – 8°C), do not freeze

سعر الجمهور بالريال ( السعر )

191.00

المصنع

SANOFI PASTEUR

الوكيل

Sanofi Arabia Trading Co. Ltd

الشركة المسوقة

SANOFI PASTEUR

كود الكيمياء العلاجية التشريحية 1

كود الكيمياء العلاجية التشريحية 2

SFDA PIL (Patient Information Leaflet (PIL) are under review by Saudi Food and Drug Authority)

1. What this product is and what it is used for

(MenACWY)^® is a vaccine that can be given to individuals from 6 weeks of age and older.

MenQuadfi^® helps to protect against infections caused by a type of bacteria (germs) called “Neisseria meningitidis”, specifically against types A, C, W and Y. Neisseria meningitidis bacteria (also called meningococci) can be passed from person to person and can cause serious and sometimes life-threatening infections, such as:

• Meningitis – an inflammation of the tissues that surround the brain and spinal cord;

• Septicaemia – an infection of the blood.

Both infections can result in serious disease with long lasting effects or possibly death.

MenQuadfi^® should be used in accordance with official national guidelines.

How the vaccine works

MenQuadfi^® works by stimulating the vaccinated person natural defence (immune system), to

produce protective antibodies against the bacteria. MenQuadfi^® only helps to protect against illnesses caused by Neisseria meningitidis types A, C, W and Y.

• It does not protect against infections caused by other types of Neisseria meningitidis.

• It does not protect against meningitis or septicaemia caused by other bacteria or viruses.

2. What you need to know before you use this product

Do not have MenQuadfi^® if you or your child

• are allergic to any of the active substances or any of the other ingredients of this vaccine (listed in

section 6) or have experienced a previous allergic reaction to this vaccine.

If you are not sure, talk to your doctor, pharmacist or nurse before you or your child are given MenQuadfi^®.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before vaccination with MenQuadfi^® if you or your child have:

• an infection with high temperature (over 38°C). If this applies, the vaccination will be given after

the infection is under control. There is no need to delay vaccination for a minor infection such as a

cold. However, talk to your doctor, pharmacist or nurse first.

• a bleeding problem or bruise easily.

• ever fainted from an injection. Fainting, sometimes accompanied by falling, can occur (mostly in adolescents) after, or even before, any injection.

• a weak immune system (such as due to HIV infection, other disease, or use of a medicine that

affect the immune system), as you or your child may not fully benefit from having MenQuadfi^®.

If any of the above apply to you or your child (or you are not sure whether they apply), talk to your doctor, pharmacist or nurse before you or your child are given MenQuadfi^®.

As with any vaccine, MenQuadfi^® may not fully protect all the peoplewho are vaccinated.

Other medicines and MenQuadfi^®

Tell your doctor, pharmacist, or nurse if you or your child are taking, have recently taken or might take any other vaccines or medicines, including medicines obtained without a prescription.

In particular, tell your doctor, pharmacist, or nurse if you or your child are taking any medicines that affect your immune system, such as:

• high-dose corticosteroids

• chemotherapy.

MenQuadfi^® may be given at the same time as other vaccines at separate injection site during the same visit. These include measles, mumps, rubella, varicella, diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b, hepatitis B, pneumococcal, human papillomavirus, rotavirus and Neisseria meningitidis type B vaccines.

Pregnancy and breast-feeding

If you are pregnant, breast-feeding, think you may be pregnant, or are planning to have a baby, ask

your doctor, pharmacist, or nurse for advice before receiving MenQuadfi^®.

Driving and using machines

MenQuadfi^® is not likely to affect your ability to drive, cycle or use machines. However, do not drive, cycle or use any machines if you are not feeling well.

MenQuadfi^® contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dose, this means that it is essentially

‘sodium-free’

3. How to use this product.

MenQuadfi^® is given by a doctor or nurse as a 0.5 mlinjection in the muscle. It is given in the upper arm or in the thigh depending on the age and how much muscle you or your child have.

4. Possible side effects

Like all vaccines, MenQuadfi^® can cause side effects, although not everybody gets them.

If you or your child get any of these symptoms after the vaccination:

• itchy skin rash

• difficulty breathing, shortness of breath

• swelling of the face, lips, throat or tongue.

Contact your doctor or healthcare professional immediately or go to the nearest hospital emergency room right away. This could be signs of an allergic reaction.

Possible side effects in infants from 6 weeks to less than 12 months of age:

Very common (may affect more than 1 in 10 people)

• tenderness, redness, or swelling where the injection was given

• feeling irritable

• crying

• loss of appetite

• feeling drowsy

• fever

• vomiting

Common (may affect up to 1 in 10 people)

• bruising where the injection was given

Uncommon (may affect up to 1 in 100 people)

• bleeding, collection of blood under the skin, lump, hardening, warmth, or rash where the injection

was given

• inflammation of the nose and throat

• diarrhea

Rare (may affect up to 1 in 1000 people)

• sudden, severe allergic reactions with difficulty breathing, hives, swelling of the face and throat, a fast heartbeat, dizziness, weakness, sweating and loss of consciousness

• nose and throat infection, runny or stuffy nose

• fits (convulsions) with fever

• cough

• constipation

• tiny blood spots under the skin, itchy rash, reddening of the skin, rash, rash with flat reddened

area, itchy, red and dry skin

• discolouration, reaction or scab where the injection was given

Possible side effects in children aged 12 to 23 months:

Very common (may affect more than 1 in 10 children)

• tenderness, redness, or swelling where the injection was given

• feeling irritable

• crying

• loss of appetite

• feeling drowsy

Common (may affect up to 1 in 10 children):

• fever

• vomiting

• diarrhoea

Uncommon (may affect up to 1 in 100 people):

• difficulty sleeping

• hives

• itching, bruising, firmness, or rash where the injection was givenVery Rare (may affect less than 1 in 10,000 people):

• sudden, severe allergic reactions with difficulty breathing, hives, swelling of the face and throat, a

• fast heartbeat, dizziness, weakness, sweating and loss of consciousness

Not known (frequency cannot be estimated from the available data):

• allergic reaction

Possible side effects in children (2 years of age and older), adolescents and adults:

Very common (may affect more than 1 in 10 people)

• pain where the injection was given

• muscle pain

• headache

• generally feeling unwell

Common (may affect up to 1 in 10 people)

• redness or swelling where the injection was given

• fever

Uncommon (may affect up to 1 in 100 people)

• itching, warmth, bruising or rash where the injection was given

• vomiting

• feeling dizzy

• nausea

• fatigue (feeling tired)

Rare (may affect up to 1 in 1,000 people)

• enlarged lymph nodes

• diarrhoea, stomach pain

• hives, itching, rash

• pain in the arms or legs

• chills, pain in the armpit

• injection site firmness

Very Rare (may affect less than 1 in 10,000 people):

• sudden, severe allergic reactions with difficulty breathing, hives, swelling of the face and throat, a fast heartbeat, dizziness, weakness, sweating and loss of consciousness

Not known (frequency cannot be estimated from the available data):

• allergic reaction

Reporting of side effects

If you or your child get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via The National Pharmacovigilance Center (NPC). By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store this product

Keep this vaccine out of the sight and reach of children. Do not use this vaccine after the expiry date which is stated on the carton after EXP.

Store in a refrigerator (2°C to 8°C). Do not freeze.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

6. Further information

a. What this product contains

One dose (0.5 ml) contains:

• The active substances are:

Neisseria meningitidis group A polysaccharide¹ 10 micrograms,

Neisseria meningitidis group C polysaccharide¹ 10 micrograms,

Neisseria meningitidis group Y polysaccharide¹ 10 micrograms,

Neisseria meningitidis group W polysaccharide¹ 10 micrograms.

¹ Conjugated to tetanus toxoid carrier protein 55 micrograms.

• The other ingredients are

sodium chloride

sodium acetate

water for injections

b. What this product looks like and contents of the pack

MenQuadfi® is a clear colourless solution for injection. MenQuadfi® is available in packs of 1, 5 or 10 single dose (0.5 mL) vials and pack of 1 single dose vial (0.5 mL) co-packaged with 1 single use empty syringe and 2 needles. Not all pack sizes may be marketed.

c. Marketing Authorization Holder and Manufacturer

a. MAH and Manufacturer:

Sanofi Pasteur Inc., Swiftwater, PA 18370 USA

a. To report any side effect(s):

· Saudi Arabia:

· The National Pharmacovigilance Center (NPC):

- SFDA Call Center: 19999

- E-mail: npc.drug@sfda.gov.sa

- Website: https://ade.sfda.gov.sa/

· Sanofi Pharmacovigilance:

- +966-54-428-4797

- KSA_Pharmacovigilance@sanofi.com

Other GCC states:

- Please contact the relevant competent authority

a. This leaflet was last revised (it will be added upon SFDA approval)

This is a Medicament

- Medicament is a product which affects your health and its consumption contrary to instructions is dangerous for you.

- Follow strictly the doctor’s prescription, the method of use and the instructions of the pharmacist who sold the medicament.

- The doctor and the pharmacist are the experts in medicines, their benefits and risks.

- Do not by yourself interrupt the period of treatment prescribed for you.

- Do not repeat the same prescription without consulting your doctor.

- Keep all medicaments out of reach of children.

Council of Arab Health Ministers

Union of Arab Pharmacists

g. This patient information leaflet is approved by the Saudi Food and Drug Authority

d. This leaflet was last revised in {MM/YYYY}

d. This leaflet was last revised (it will be added upon SFDA approval)

نشرة الدواء تحت مراجعة الهيئة العامة للغذاء والدواء (اقرأ هذه النشرة بعناية قبل البدء في استخدام هذا المنتج لأنه يحتوي على معلومات مهمة لك)

1. ما ھو هذا المستحضر وماھي دواعي استعماله

مينكوادفي (MenACWY)^® هو لقاح يمكن إعطاؤه للأفراد من عمر 6 أسابيع وما فوق.

يساعد مينكوادفي على الحماية من الإصابات الناجمة عن نوع من البكتيريا (الجراثيم) المسماة بالنسيرية السحائية "Meningitidis Neisseria"، خاصة ضد أنواع A، C، W و Y. قد تنتقل بكتيريا النسيرية السحائية (المسماة أيضاً مرض المكورات السحائية) من شخص الى آخر وقد تتسبب في إصابات خطيرة وقد تكون أحيانا مميتة، مثل:

· إلتهاب السحايا – إلتهاب الأنسجة المحيطة بالدماغ والحبل الشوكي؛

· تسمم دموي – تعفن الدم.

كلتا الإصابتين قد تتسبب في مرض خطير بتأثيرات طويلة الأمد ومن المحتمل ان تسبب الوفاة.

يجب استعمال مينكوادفي طبقا للتوصيات والتوجيهات الوطنية الرسمية.

كيفية عمل اللقاح

يعمل مينكوادفي على تحفيز نظام الدفاع الطبيعي للشخص الملقح (الجهاز المناعي)، لإنتاج مضادات الأجسام الوقائية ضد البكتيريا. يساعد مينكوادفي فقط في الحماية ضد الأمراض الناجمة عن النسيرية السحائية من أنواع A، C، W وY.

· لا يحمي من الإصابات الناتجة عن أنواع أخرى من النسيرية السحائية.

· لا يحمي من إلتهاب السحايا أو التسمم الدموي الناتج عن بكتيريا أو فيروسات آخرى.

2. ما الذي يجب عليك معرفته قبل استعمال هذا المستحضر

لا تستعمل مينكوادفي إذا كانت لديك أو لدى طفلك

· حساسية لأي من المواد الفعالة أو المكونات الآخرى للقاح (المذكورة في الفقرة 6) أو عانيت من تفاعل تحسسي سابق لهذا اللقاح.

في حالة الشك، تحدث الى الطبيب أو الصيدلي أو الممرض قبل أن تحصل أنت أو طفلك على مينكوادفي.

تحذيرات واحتيطات

تحدث الى الطبيب أو الصيدلي أو الممرض قبل التلقيح بمينكوادفي إذا كنت تعاني أنت أو طفلك من:

· إصابة بدرجة حرارة عالية (أكثر من 38 درجة مئوية). إذا كان الأمر كذلك، سيتم التلقيح بعد التحكم في الإصابة. لا داعي لتأجيل التلقيح بسبب مرض طفيف مثل الزكام. رغم ذلك، تحدث أولاً الى الطبيب أو الصيدلي أو الممرض.

· مشكلة النزيف أو الإصابة بالكدمات بسهولة.

· إغماء سابق إثر الحقن. قد يحدث الإغماء المصحوب أحيانا بالسقوط (غالبا لدى المراهقين) بعد أو حتى قبل أية حقنة.

· جهاز مناعي ضعيف (مثلاً بسبب الإصابة بفيروس نقص المناعة البشرية، بمرض آخر أو بسبب استعمال دواء يؤثر سلباً على الجهاز المناعي)، لأنك قد لا تستفيد أنت أو طفلك كلياً من مينكوادفي.

إذا كنت أنت او طفلك معنياً بالحالات أعلاه (أو في حالة الشك أنها تنطبق عليك)، تحدث الى الطبيب أو الصيدلي أو الممرض قبل أن تحصل أنت أو طفلك على مينكوادفي.

كما هو الشأن مع أي لقاح، قد لا يحمي مينكوادفي تماماً جميع الأشخاص الذين يتمّ تطعيمهم.

أدوية آخرى ومينكوادفي

اخبر الطبيب أو الصيدلي او الممرض إذا حصلت أنت أو طفلك أو قد تحصل على أية لقاحات أو أدوية آخرى. بما فيها الأدوية التي يمكن الحصول عليها دون وصفة طبية.

وبشكل خاص، اخبر الطبيب أو الصيدلي أو الممرض إذا كنت تتناول أنت أو طفلك أية أدوية قد تؤثر سلباً على جهازك المناعي، مثل:

· كورتيكوستيرويدات عالية الجرعة.

· العلاج الكيماوي.

يمكن الحصول على مينكوادفي في نفس الوقت مع لقاحات آخرى في موقع حقن مختلف خلال نفس الزيارة. بما في ذلك لقاحات الحصبة، النكاف، الحصبة الألمانية، جدري الماء، الخناق، الكزاز، السعال الديكي، شلل الأطفال، النزلة النزفية من نوع ب، التهاب الكبد ب، الإصابات بالمكورات الرئوية وبفيروس الورم الحليمي البشري وفيروس الروتا، والنيسرية السحائيّة من النوع ب.

الحمل والرضاعة

إذا كنتِ حاملاً أو ترضعين، إذا اعتقدتِ أنكِ حامل أو تنوين الحمل، استشيري الطبيب أو الصيدلي أو الممرض قبل الحصول على مينكوادفي.

قيادة السيارات واستعمال الآلات

من غير المحتمل أن يؤثر مينكوادفي على قدرتك على قيادة السيارات أو الدراجات أو استعمال الآلات. لكن إذا لم تشعر بحالة جيدة، لا تقد السيارة أو الدراجة ولا تستعمل أية آلة.

يحتوي مينكوادفي على الصوديم

يحتوي هذا الدواء على أقل من 1 ملليمول (23 ملجم) من الصوديوم لكل جرعة، أي يعتبر أساسا "خالي من الصوديوم".

https://localhost:44358/Dashboard 3. ماھي طريقة استعمال هذا المستحضر

يقوم الطبيب أو الممرض بمنح مينكوادفي في حقنة 0.5 ملل في العضلة. وتستعمل في أعلى الذراع أو الفخذ حسب السن وكتلة العضلة لديك أو لدى طفلك.

4. الأعراض الجانبية المحتملة

1. الأعراض الجانبيّة المحتملة

كمثل كافة اللقاحات، قد يتسبب مينكوادفي في تأثيرات غير مرغوب فيها، رغم عدم ظهورها لدى جميع الأشخاص.

إذا عانيت أنت أو طفلك من أحد هذه الأعراض بعد التلقيح:

· طفح جلدي مصحوب بحكة

· صعوبة في التنفّس، ضيق التنفس

· انتفاخ الوجه أو الشفتين أو الحلق أو اللسان

اتصل بطبيبك أو بأخصّائي الرعاية الصحيّة على الفور أو اذهب إلى أقرب قسم طوارئ في المستشفى على الفور. قد تكون هذه علامات تفاعل تحسسي.

التأثيرات الجانبيّة المحتملة لدى الأطفال الرضّع ابتداءً من 6 أسابيع إلى أقلّ من 12 شهراً:

شائعة جداً (قد تصيب أكثر من شخص من كلّ 10 أشخاص)

· ألم أو احمرار أو تورّم في موضع الحقنة

· شعور بالعصبيّة

· بكاء

· فقدان الشهيّة

· شعور بالنعاس

· حمى

· قيء

شائعة (قد تصيب لغاية شخص واحد من كلّ 10 أشخاص)

· كدمات في موضع الحقنة

غير شائعة (قد تصيب لغاية شخص واحد من كلّ 100 شخص)

· نزيف أو تجمّع دم تحت الجلد أو تكتل أو تصلّب أو سخونة أو طفح جلدي في موضع الحقنة

· التهاب الأنف والحلق

· إسهال

نادرة (قد تصيب لغاية شخص واحد من كلّ 1000 شخص)

· ردود فعل تحسسيّة مفاجئة وشديدة مع صعوبة في التنفّس، شرى، تورّم الوجه والحلق، ضربات قلب سريعة، دوار، ضعف، تعرّق وفقدان الوعي

· التهاب الأنف والحلق، سيلان الأنف أو انسداده

· نوبات (تشنّجات) مصحوبة بحمى

· سعال

· إمساك

· بقع دمويّة صغيرة تحت الجلد، طفح جلدي مثير للحكّة، احمرار في الجلد، طفح جلدي، طفح جلدي مع منطقة مسطّحة محمرّة، حكّة واحمرار وجفاف في الجلد

· تغيّر في اللون أو ردّ فعل أو تقشّر في موضع الحقنة

التأثيرات غير المرغوب فيها المحتملة لدى الأطفال ما بين 12 و 23 شهراً:

شائعة جداً (قد تصيب أكثر من طفل من كل 10 أطفال)

· ألم أو احمرار أو انتفاخ في موضع الحقنة

· شعور بالعصبية

· بكاء

· فقدان الشهية

· شعور بالنعاس

شائعة (قد تصيب لغاية طفل من كل 10 أطفال)

· حمى

· قيء

· إسهال

غير شائعة (قد تصيب لغاية شخص من كل 100 أشخاص)

· صعوبة في النوم

· شرى

· حكة، كدمات، تصلب أو طفح في موضع الحقنة.

نادرة جدًا (قد تصيب أقلّ من شخص واحد من كلّ 10000 شخص):

· ردود فعل تحسسيّة مفاجئة وشديدة مع صعوبة في التنفّس، شرى، تورّم في الوجه والحلق،

· ضربات قلب سريعة، دوار، ضعف، تعرّق وفقدان الوعي

غير المعروفة (لا يمكن تقييم عدد مرّات حصولها من البيانات المتاحة):

· ردّ فعل تحسسي

التأثيرات غير المرغوب فيها المحتملة لدى الأطفال (سنتيْن وما فوق) والمراهقين والبالغين:

شائعة جداً (قد تصيب أكثر من شخص من كل 10)

· ألم في موضع الحقنة

· ألم العضلات

· صداع

· عدم الشعور بحالة جيدة عموماً

شائعة (قد تصيب لغاية شخص من كل 10)

· احمرار أو انتفاخ في موضع الحقنة

· حمى

غير شائعة (قد تصيب لغاية شخص من كل 100)

· حكة، دفء، كدمات أو طفح في موضع الحقنة

· قيء

· شعور بالدوار

· غثيان

· شعور بالتعب

نادرة (قد تصيب لغاية شخص من أصل 1000)

· تضخم العقد اللمفاوية

· إسهال، ألم المعدة

· شرى، حكة، طفح

· ألم في الذراعين أو الساقين

· قشعريرة، ألم في الإبطين

· تصلب موضع الحقنة

نادرة جدًا (قد تصيب أقلّ من شخص واحد من كلّ 10000 شخص):

· ردود فعل تحسسيّة مفاجئة وشديدة مع صعوبة في التنفّس، شرى، تورّم في الوجه والحلق، ضربات قلب سريعة، دوار، ضعف، تعرّق وفقدان الوعي

غير المعروفة (لا يمكن تقييم عدد مرّات حصولها من البيانات المتاحة):

· ردّ فعل تحسسي

الإبلاغ عن الأعراض الجانبية

إذا شعرت أنت أو طفلك بأي تأثير غير مرغوب فيه، أخبر الطبيب أو الصيدلي أو الممرّض. وينطبق ذلك أيضًا على أيّ تأثيرات جانبيّة لم تُذكر في هذه النشرة. يمكنك أيضًا الإبلاغ عن التأثيرات الجانبيّة مباشرةً عبر المركز الوطني للتيّقظ والسلامة الدوائيّة (NPC). من خلال الإبلاغ عن التأثيرات الجانبيّة، يمكنك المساعدة في توفير المزيد من المعلومات حول سلامة هذا الدواء.

5. طريقة تخزين المستحضر

1. طريقة تخزين مينكوادفي

يحفظ هذا اللقاح بعيداً عن متناول ومرأى الأطفال. لا تستعمل هذا اللقاح بعد تاريخ انتهاء الصلاحية المدون على العلبة بعد عبارة EXP.

يُحفظ في الثلاجة (ما بين 2 إلى 8 درجات مئوية). لا يُجمّد.

يجب عدم رمي الأدوية في المجاري الصحيّة أو مع النفايات المنزلية. اسأل الصيدلي عن طريقة التخلص من الأدوية غير المستعملة. ستساهم هذه التدابير في حماية البيئة.

6. معلومات أخرى

أ‌. على ماذا يحتوي هذا المستحضر

تحتوي جرعة واحدة (0.5 ملل) على:

· المواد الفعالة التالية:

النسيرية السحائية مجموعة A عديد السكاريد¹ 10 ميكروجرام،

النسيرية السحائية مجموعة C عديد السكاريد¹ 10 ميكروجرام،

النسيرية السحائية مجموعة Yعديد السكاريد¹ 10 ميكروجرام،

النسيرية السحائية مجموعة W عديد السكاريد¹ 10 ميكروجرام،

¹مقترن بالبروتين الناقل لتوكسويد الكزاز 55 ميكروجرام.

· المكونات الآخرى هي:

كلوريد الصوديوم

أسيتات الصوديوم

ماء خاص بالحقن

ب‌. كيف يبدو شكل هذا المستحضر وماهي محتويات العلبة

ما شكل مينكوادفي وما محتويات العبوة الخارجية

مينكوادفي محلول صافي عديم اللون للحقن. مينكوادفي متوفر في عبوات تحتوي على 1 أو 5 أو 10 قوارير ذات جرعة واحدة (0.5 ملل) وعبوة مكوّنة من قارورة واحدة ذات جرعة واحدة (0.5 ملل) مع محقنة فارغة للاستخدام مرّة واحدة وإبرتيْن.

قد لا تكون جميع أحجام العبوات مسوّقة.

ت‌. الشركة المصنعة ومالك حق التسويق

ج. حامل رخصة التسويق والمصنع:

Sanofi Pasteur Inc., Swiftwater, PA 18370 USA

للإبلاغ عن الأعراض الجانبية:

· المملكة العربية السعودية:

· المركز الوطني للتيقظ الدوائي:

- مركز الإتصال الموحد: 19999

- البريد الإلكتروني: npc.drug@sfda.gov.sa

- الموقع الإلكتروني: https://ade.sfda.gov.sa

· سانوفي للتيقظ الدوائي:

- +966-54-428-4797

KSA_Pharmacovigilance@sanofi.com

دول الخليج العربي الأخرى:

الرجاء الإتصال بالجهات الوطنية المختصة

مجلس وزراء العرب

إن هذا الدواء

- الدواء مستحضر يؤثر على صحتك واستهلاكه خلافاً للتعليمات يعرضك للخطر.

- اتبع بدقة وصفة الطبيب، وطريقة الإستعمال المنصوص عليها، وتعليمات الصيدلي الذي صرفها لك.

- الطبيب والصيدلي هما الخبيران في الدواء، وفي نفعه وضرره.

- لا تقطع مدة العلاج المحددة لك من تلقاء نفسك.

- لا تكرر صرف الدواء بدون استشارة الطبيب المختص.

- لا تترك الأدوية في متناول الأطفال.

مجلس وزراء الصحة العرب

واتحاد الصيادلة العرب

و تمت الموافقة على هذه النشرة من قبل الهيئة العامة للغذاء والدواء.

ث‌. تمت مراجعة هذه النشرة في التاريخ الذي تمت فيه مراجعة النشرة بالشهر والسنة

د. آخر تاريخ تمت فيه مراجعة النشرة (ستتمّ إضافته بعد موافقة الهيئة العامة للغذاء والدواء)

Read this leaflet carefully before you start using this product as it contains important information for you

1. NAME OF THE MEDICINAL PRODUCT

MenQuadfi solution for injection Meningococcal Group A, C, W and Y conjugate vaccine MenACWY

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

One dose (0.5 mL) contains: Neisseria meningitidis group A polysaccharide1 10 micrograms Neisseria meningitidis group C polysaccharide1 10 micrograms Neisseria meningitidis group W polysaccharide1 10 micrograms Neisseria meningitidis group Y polysaccharide1 10 micrograms 1Conjugated to tetanus toxoid carrier protein 55 micrograms For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for injection. Clear colourless solution.

4. CLINICAL PARTICULARS

4.1 Therapeutic Indications

MenQuadfi is indicated for active immunisation of individuals from the age of 6 weeks and older against invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W, and Y.

The use of this vaccine should be in accordance with available official recommendations.

4.2 Posology And Method Administration

Posology

Primary vaccination:

• Infants from 6 weeks of age: Three doses (each of 0.5 mL) should be administered with an interval of at least 2 months.

• Individuals 6 months of age and older: One single dose (0.5 mL).

Booster vaccination:

• After completion of the primary immunisation series prior to 12 months of age, a booster dose

should be given in the second year of life (from 12 months of age) at least 2 months after the last

dose (see section 5.1).

• A single 0.5 mL dose of MenQuadfi may be used to boost individuals 12 months of age

• and older who have previously received a meningococcal vaccine containing the same serogroups (see section 5.1).

• Long-term antibody persistence data following vaccination with MenQuadfi are available up to 7 years after vaccination (see sections 4.4 and 5.1).

Other paediatric population

Safety and effectiveness of MenQuadfi were established in individuals from 6 weeks through 17 years of age. Data from MET41, MET42 and MET58 indicate that MenQuadfi can be given to infants with a history of preterm birth. The safety of MenQuadfi was evaluated in 237 infants with a history of preterm birth and no differences in adverse reactions following MenQuadfi were found between these infants and

those who were born full term (see Section 4.8 Undesirable effects). Additionally, the immune responses to MenQuadfi evaluated in 61-71 infants with a history of preterm birth (MET42) were comparable to those infants who were born full term. Infants with a history of preterm birth whose clinical condition is

satisfactory should be immunized with full doses of vaccine at same chronological age and according to the same schedule as full-term infants, regardless of birth weight.

Method of administration

For intramuscular injection only, preferably in the deltoid region or anterolateral thigh depending on the recipient's age and muscle mass.

For instructions on handling of the vaccine before administration, see section 6.6.

4.3 Contraindications

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1 or after previous administration of the vaccine or a vaccine containing the same components.

4.4. Special warnings and precautions for use

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

MenQuadfi should not be administered subcutaneously, intravascularly or intradermally.

It is good clinical practice to precede vaccination by a review of the medical history (especially with regard to previous vaccination and possible occurrence of undesirable effects) and a clinical examination.

Hypersensitivity

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following administration of the vaccine.

Intercurrent illness

Vaccination should be postponed in individuals suffering from an acute severe febrile illness. However, the presence of a minor infection, such as cold, should not result in the deferral of vaccination.

Syncope

Syncope (fainting) and other anxiety‐related reactions can occur following or even before any vaccination as a psychogenic response to the needle injection. Procedures should be in place to prevent falling or injury and to manage syncope.

Thrombocytopenia and coagulation disorders

MenQuadfi should be given with caution to individuals with thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injection, unless the potential benefit clearly outweighs the risk of administration.

Protection

MenQuadfi will only protect against Neisseria meningitidis groups A, C, W, and Y. The vaccine will not protect against any other Neisseria meningitidis groups.

As with any vaccine, vaccination with MenQuadfi may not protect all vaccine recipients.

Waning of serum bactericidal antibody titres against serogroup A when using human complement in the

assay (hSBA) has been reported for MenQuadfi and other quadrivalent meningococcal vaccines. The clinical relevance of this observation is unknown. However, if an individual is expected to be at particular risk of exposure to serogroup A and received a dose of MenQuadfi more than approximately one year previously, consideration may be given to administering a booster dose.

Lower hSBA geometric mean titres (GMTs) against serogroup A have been observed after a single dose

of MenQuadfi was administered to toddlers who previously received serogroup C meningococcal conjugate vaccine (MenC-CRM) during infancy. Nevertheless, seroprotection rates were comparable

between treatment groups (see section 5.1). The clinical relevance of this observation is unknown. This

aspect might be considered for individuals at high risk for MenA infection who received MenC-CRM

vaccine in their first year of life.

Immunodeficiency

It may be expected that in patients receiving immunosuppressive treatment or patients with immunodeficiency, an adequate immune response may not be elicited (see section 4.5). Persons with

familial complement deficiencies (for example, C5 or C3 deficiencies) and persons receiving treatments

that inhibit terminal complement activation (for example, eculizumab) are at increased risk of invasive

disease caused by Neisseria meningitidis groups A, C, W, and Y, even if they develop antibodies

following vaccination with MenQuadfi. No data on immunocompromised patients are available.

Tetanus immunisation

Immunisation with MenQuadfi vaccine does not substitute for routine tetanus immunisation. Co-administration of MenQuadfi with a tetanus toxoid-containing vaccine does not impair the response to tetanus toxoid or impact the safety.

Sodium content

This medicine contains less than 1 mmol sodium (23 mg) per dose that is to say essentially ‘sodium-free’.

4.5. Interactions with other medicinal products

Use with other vaccines

Injection sites on separate limbs and separate syringes must be used in the case of concomitant administration.

For ages 6 weeks through-23 months, MenQuadfi can be co-administered with the measles-mumps-rubella vaccine (MMR) +varicella vaccine (V), combined diphtheria - tetanus - acellular pertussis (DTaP) vaccines, including combination DTaP vaccines with hepatitis B (HBV), inactivated poliovirus (IPV) or Haemophilus influenzae type b (Hib) such as DTaP-IPV-HB-Hib or DTaP-IPV/Hib (Hib conjugated to tetanus toxoid) vaccine 13-valent pneumococcal polysaccharide conjugated vaccine (PCV-13) and rotavirus vaccine.

There was no impact on the immune response to MenQuadfi when a meningococcal serogroup B vaccine was co-administered.

MenQuadfi can be administered concomitantly with PCV-13. Lower hSBA GMTs on day 30 post-dose for serogroup A have been observed when given concomitantly. The clinical relevance of this observation is unknown. As a precaution in children 12-23 months of age at high risk for serogroup A disease, consideration might be given for administration of MenQuadfi and PCV-13 vaccines separately.

For ages 10‑17 years, MenQuadfi can be co-administered with diphtheria, tetanus, pertussis (acellular, component) vaccine (adsorbed, reduced antigen(s) content) (Tdap), or Tdap and inactivated poliovirus vaccine (Tdap-IPV), and 4-valent human papillomavirus vaccine (recombinant, adsorbed) (4vHPV) or 9‑valent HPV vaccine (9vHPV). However, the antibody responses to some of the antigens might be affected by the co-administration.

Meningococcal vaccine naïve children and adolescents aged 10-17 years had non inferior response for PT and lower antibody responses to FHA, PRN and FIM when Tdap vaccine was administered concomitantly with MenQuadfi and 4vHPV compared to co-administration with 4vHPV vaccine alone (immune response assessed after the full series of HPV was completed). The clinical implications of the observed pertussis antigen responses also observed with other quadrivalent meningococcal conjugate vaccines are unknown.

The co-administration of MenQuadfi with Tdap-IPV and 9vHPV in children and adolescents aged 10‑17 years resulted in lower GMTs and seroresponse rates for serogroup A, lower GMTs for serogroup W, lower responses to inactivated polio types 1 and 3, diphtheria, and anti-HPV types 6 and 58 (immune response assessed after the first dose of 9vHPV) compared to when MenQuadfi was given sequentially with Tdap-IPV and 9vHPV. The clinical implication of the observed reduced titre responses is unclear. Consideration might be given for sequential administration of MenQuadfi with Tdap-IPV and 9vHPV (e.g. for children and adolescents at higher risk).

Concomitant vaccines should always be administered at separate injection sites and preferably contralateral.

Concomitant administration of MenQuadfi and other vaccines than those listed above has not been studied.

Use with systemic immunosuppressive medicinal products

It may be expected that in patients receiving immunosuppressive treatment an adequate immune response may not be elicited (see also section 4.4).

4.6. Fertility, pregnancy and lactation

Pregnancy

There is limited amount of data on the use of MenQuadfi in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

MenQuadfi should be used during pregnancy only if the expected benefits for the mother outweigh the potential risks, including those for the foetus.

Breast-feeding

It is unknown whether MenQuadfi is excreted in human milk. MenQuadfi should only be used during breast-feeding when the possible advantages outweigh the potential risks.

Fertility

A developmental and reproductive toxicity study was performed in female rabbits. There were no effects on mating performances or female fertility. No study was conducted on male fertility (see section 5.3).

4.7. Effects on ability to drive and use machines

MenQuadfi has no or negligible influence on the ability to drive and use machines.

However, some of the effects mentioned under section 4.8 “Undesirable effects” may temporarily affect the ability to drive or use machines.

4.8. Undesirable effects

Summary of the safety profile

The safety of MenQuadfi in infants initiating vaccination from 6 weeks of age to less than 12 months of

age is based on 6 studies in which participants received at least one dose of MenQuadfi concomitantly

with routine paediatric vaccines (N=6060) or MenQuadfi concomitantly with MenB vaccine (N=314).

The routine paediatric vaccines include DTaP-IPV/Hib or DTaP-IPV-HB or DTaP-IPV-HB-Hib or DTPa-

HB-IPV/Hib, Hib vaccine, PCV13 or PCV10, rotavirus vaccine, HepB, MMR, V or HepA. These studies

evaluated the safety of a primary series consisting of either 1, 2 or 3 doses of MenQuadfi in the first year

of life, following by a booster dose from 12 months of age in the second year of life.

The most frequently reported adverse reactions within 7 days after vaccination with any dose of

MenQuadfi in infants initiating vaccination from 6 weeks of age to less than 12 months of age were

irritability (74.6%) and injection site tenderness (64.6%). These adverse reactions were mostly mild or

moderate in intensity.

The safety of a single dose of MenQuadfi in individuals 12 months of age and older was evaluated in seven randomized, active-controlled, multi-centre pivotal studies. In these studies, 6,308 subjects received either a primary dose (N=5,906) or a booster dose (N=402) of MenQuadfi and were included in the safety analyses. This included 1,389 toddlers aged 12 through 23 months of age, 498 children aged 2 through 9 years, 2,289 children and adolescents aged 10 through 17 years, 1,684 adults aged 18 through 55 years, 199 older adults aged 56 through 64 years, and 249 elderly aged 65 years and older. Of these,

392 adolescents received MenQuadfi co-administered with Tdap and 4vHPV , and 589 toddlers received MenQuadfi co-administered with MMR+V (N=189), DTaP-IPV-HB-Hib (N=200) or PCV-13 (N=200).

The most frequently reported adverse reactions within 7 days after vaccination with a single dose of MenQuadfi alone in toddlers 12 through 23 months of age were irritability (36.7%) and injection site

tenderness (30.6%) and in ages 2 years and above were injection site pain (38.7%) and myalgia (30.5%). These adverse reactions were mostly mild or moderate in intensity.

Rates of adverse reactions after a booster dose of MenQuadfi in adolescents and adults at least 15 years of age were comparable to those seen in adolescents and adults who received a primary dose of MenQuadfi.

There was no difference in the adverse reactions following routine paediatric vaccines when given

concomitantly with MenQuadfi compared to when given concomitantly with other meningococcal

vaccines in infants from 6 weeks to less than 12 months of age.

Rates of adverse reactions within 7 days following vaccination among toddlers were comparable when MMR+V were given concomitantly with or without MenQuadfi, and when DTaP-IPV-HB-Hib was given with or without MenQuadfi. Overall, the rates of adverse reactions were higher in toddlers who received PCV-13 given concomitantly with MenQuadfi (36.5%) than in toddlers who received PCV-13 alone (17.2%).

Children and adolescents aged 10-17 years of age were given either MenQuadfi alone (N=171) or MenQuadfi concomitantly with Tdap-IPV and the first dose of 9vHPV (N=116). The rates of injection site reaction pain at the 9vHPV injection site were higher when given concomitantly with Tdap-IPV and MenQuadfi (83.6%) compared to when Tdap-IPV and 9vHPV were given without MenQuadfi (67.3%). Overall, rates and intensity of adverse reactions were comparable between these two groups.

In one additional clinical study, adolescents and adults 13-26 years of age primed with MenQuadfi 3‑6 years previously received MenQuadfi co-administered with meningococcal serogroup B (MenB) vaccine, Trumenba (N=93) or Bexsero (N=92). Rates and intensity of systemic reactions within 7 days following vaccination tended to be higher when MenQuadfi was given concomitantly with MenB vaccine than when MenQuadfi was given alone. The most common solicited systemic reaction was myalgia, of mild intensity, which was experienced more frequently in adolescents and adults who received MenQuadfi and MenB vaccine concomitantly (Trumenba, 65.2%; Bexsero, 63%) compared to those who received MenQuadfi alone (32.8%).

Tabulated list of adverse reactions

The following adverse reactions, as listed below, have been identified from clinical studies conducted with MenQuadfi when given alone to subjects 2 years of age and older. The safety profiles observed in infants initiating vaccination from 6 weeks to less than 12 months of age and toddlers aged 12 through 23 months are presented in the paediatric population section.

The adverse reactions are listed according to the following frequency categories:

Very common (≥1/10); Common (≥1/100 to <1/10);

Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000).

Very Rare (<1/10,000);

Not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1: Tabulated summary of adverse reactions following administration of MenQuadfi from clinical trials and post-marketing surveillance in subjects 2 years of age and above

MedDRA System Organ Class	Frequency	Adverse reactions
Blood and lymphatic system disorders	Rare	Lymphadenopathy
Immune system disorders	Very Rare	Anaphylaxis
Immune system disorders	Not known	Hypersensitivity
Nervous system disorders	Very common	Headache
	Uncommon	Dizziness
	Not known	Febrile convulsions, seizures
Gastrointestinal disorders	Uncommon	Vomiting, nausea
Gastrointestinal disorders	Rare	Diarrhoea, stomach pain
Skin and subcutaneous tissue disorders	Rare	Urticaria, pruritus, rash
Musculoskeletal and connective tissue disorders	Very common	Myalgia
Musculoskeletal and connective tissue disorders	Rare	Pain in extremity
General disorders and administration site conditions	Very common	Malaise
	Very common	Injection site pain
	Common	Fever
	Common	At the injection site: swelling, erythema
	Uncommon	Fatigue
	Uncommon	At the injection site: pruritus, warmth, bruising, rash
	Rare	Chills, axillary pain
	Rare	At the injection site: induration

Paediatric population

The safety profile of MenQuadfi in children and adolescents 2 through 17 years of age was generally comparable to that in adults. Injection site erythema and swelling at the MenQuadfi injection site were

reported more frequently in children 2 through 9 years of age (very common) than in the older age groups.

When co-administered with routine paediatric vaccines, the safety profile of MenQuadfi when

administered as a booster dose in the second year of life was similar to its safety profile in infants from 6

weeks to less than 12 months of age. Adverse reactions following MenQuadfi vaccination in individuals

12 through 23 months of age when administered as a booster dose or a single primary dose were generally

comparable.

Table 2: Tabulated summary of adverse reactions following administration of MenQuadfi with routine paediatric vaccines from clinical trials in infants initiating vaccination from 6 weeks to less than 12 months of age

MedDRA System Organ Class	Frequency	Adverse reactions
Infections and infestations	Uncommon	Nasopharyngitis
Infections and infestations	Rare	Upper respiratory tract infection, Rhinitis
Immune system disorder	Rare	Anaphylactic reaction*
Metabolic and nutrition disorders	Very common	Appetite lost
Psychiatric disorders	Very common	Irritability
Nervous system disorders	Very common	Drowsiness
Nervous system disorders	Rare	Febrile convulsion*
Respiratory, thoracic and mediastinal disorders	Rare	Cough**
Gastrointestinal disorders	Very common	Vomiting
	Uncommon	Diarrhoea
	Rare	Constipation**
Skin and subcutaneous tissue disorders	Uncommon	Rash
Skin and subcutaneous tissue disorders	Rare	Petechiae*, urticaria, erythema, rash, macular, eczema
General disorders and administration site conditions	Very common	Fever
		Abnormal crying
		At the injection site tenderness/pain, erythema, swelling
	Common	At the injection site: bruising
	Uncommon	At the injection site: haemorrhage, heamatoma, mass, induration, warmth, rash
	Rare	At the injection site: discolouration, reaction, scab**

*Occurred at a frequency of < 0.1% in one subject from 12-18 months of age

** Occurred at frequency of <0.1% and more ≥3 subjects experiencing the event

*** Petechiae occurred at a frequency of <0.1% in one subject from 6 weeks to less than 12 months

In toddlers 12 through 23 months of age, injection site erythema and swelling (very common) at the MenQuadfi injection site, vomiting (common) and diarrhoea (common), were reported more frequently than in the older age groups. The following additional reactions, as listed below in Table 3, have been reported following administration of MenQuadfi in toddlers during clinical trials and post-marketing surveillance:

Table 3: Tabulated summary of adverse reactions following administration of MenQuadfi from clinical trials and post-marketing surveillance in subjects 12 months through 23 months

MedDRA System Organ Class	Frequency	Adverse reactions
Immune system disorders	Very Rare	Anaphylaxis
Immune system disorders	Not known	Hypersensitivity
Metabolic and nutrition disorders	Very common	Appetite lost
Psychiatric disorders	Very common	Irritability
Psychiatric disorders	Uncommon	Insomnia
Nervous system disorders	Very common	Drowsiness
Nervous system disorders	Not known	Febrile convulsions, seizures
Gastrointestinal disorders	Common	Vomiting, diarrhoea
Skin and subcutaneous tissue disorders	Uncommon	Urticaria
General disorders and administration site conditions	Very Common	Abnormal crying
	Very Common	At the injection site: tenderness/pain, erythema, swelling
	Common	Fever
	Uncommon	At the injection site: pruritus, induration, bruising, rash

Older population

Overall, within 7 days after vaccination with a single dose of MenQuadfi, the same injection site and systemic adverse reactions were observed in older (≥56 years of age) and younger adults (18 through 55 years old) but at lower frequencies; except for injection site pruritus, which was more frequent (common) in older adults. These adverse reactions mostly were mild or moderate in intensity.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.

To reports any side effect(s):

Saudi Arabia:

· The National Pharmacovigilance Centre (NPC):

- SFDA Call Center: 19999

- E-mail: npc.drug@sfda.gov.sa

- Website: https://ade.sfda.gov.sa/

Other GCC States:

- Please contact the relevant competent authority.

Sanofi Pharmacovigilance:

- KSA_Pharmacovigilance@sanofi.com

For any other medical inquiry:

- KSA.Medicalenquiry@sanofi.com

4.9. Overdoes

Overdose with MenQuadfi is unlikely due to its presentation as a single dose vial. In the event of overdose, monitoring of vital functions and possible symptomatic treatment is recommended.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic Properties

Pharmacotherapeutic group: meningococcal vaccines ATC code: J07AH08

Mechanism of action

Anti-capsular meningococcal antibodies protect against meningococcal diseases via complement mediated bactericidal activity.

MenQuadfi induces the production of bactericidal antibodies specific to the capsular polysaccharides of

Neisseria meningitidis serogroups A, C, W, and Y.

Immunogenicity

The immunogenicity of MenQuadfi in infants initiating vaccination from 6 weeks to less than 12 months

of age was assessed in two pivotal studies where the primary vaccination series consisted of one or three

doses in the first year of life (depending on the age at first dose) and a booster dose in the second year of

life. The immunogenicity of a single dose of MenQuadfi for primary vaccination in toddlers (12-23 months of age), children and adolescents (2-17 years of age), adults (18-55 years of age) and older adults (56 years and above) was assessed in six pivotal studies and in two additional studies in toddlers (12 23 months of age) and children and adolescents (10-17 years of age). The immunogenicity of a single dose of MenQuadfi when used as a booster vaccination was assessed in one pivotal study (subjects 15-55 years of age) and in four additional studies: two in children 3 years and 5 years after primary vaccination as toddlers 12 through 23 months of age, one in adolescents and adults 3-6 years after primary vaccination, and one in older adults 3, 5 and 6-7 years after primary vaccination at ≥ 56 years of age. In addition, clinical data on the persistence of antibody response from at least 3 years and up to 7 years after primary vaccination with MenQuadfi are available in these additional studies.

Primary immunogenicity analyses were conducted by measuring serum bactericidal activity (SBA) using human serum as the source of exogenous complement (hSBA). Rabbit complement (rSBA) data are available in subsets in all age groups and generally follows the trends observed with human complement (hSBA) data. In addition, all subjects were assessed for primary immunogenicity measured by hSBA and rSBA for serogroup C in MEQ00065 study [NCT03890367].

Immunogenicity in infants initiating vaccination from 6 weeks through 6 months of age

MET42 (NCT03537508) compared the immunogenicity of three doses (given at 2, 4, and 6 months of

age) and a booster dose (given at 12-18 months of age) of MenQuadfi to that of MenACWY-CRM 30

days after the third and booster vaccination. The percentage of participants with hSBA titres ≥ 1:8

(seroprotection rate), hSBA seroresponse rate, and GMTs are presented in Table 4.

Immune non-inferiority, based on seroresponse rates, after the booster dose was demonstrated for

MenQuadfi as compared to MenACWY-CRM for all four serogroups.

Immune non-inferiority, based on seroprotection rates, after the third dose was demonstrated for

MenQuadfi as compared to MenACWY-CRM for all four serogroups.

Table 4: Comparison of bactericidal antibody responses to MenQuadfi and MenACWY-CRM 30

days after vaccination with routine infant vaccines at 2, 4, and 6 months and a booster dose at 12-18 months (study MET42*)

Post 3^rd Dose

Pre booster dose

Post booster dose

Endpoint

MenQuadfi (95% CI)

MenACWY- CRM

(95% CI)

MenQuadfi (95% CI)

MenACWY- CRM

(95% CI)

MenQuadfi (95% CI)

MenACWY- CRM

(95% CI)

N=682- 852

N=322-409

N=607

N=282

N=501- ~~462~~642

N=223-296

% ≥1:8

(Seroprotection)^‡

77.9 (75.0;

80.7)

67.7 (63.0;

72.2)

62.8 (58.8;

66.6)

46.5 (40.5;

52.5)

87.7 (84.9;

90.1)

88.2 (83.9;

91.6)

Seroresponse^†‡

64.4 (60.6;

68.0)

50.6 (45.0;

56.2)

79.4 (75.6;

82.9)

77.6 (71.5;

82.9)

hSBA GMT

25 (23; 28)

15 (13; 18)

11 (10; 12)

7 (6; 8)

67 (58; 78)

57 (47; 70)

N=691- 835

N=338-421

N=612

N=284

N=530-655

N=238-300

% ≥1:8

(Seroprotection)^‡

99.0 (98.1;

99.6)

91.2 (88.1;

93.7)

93.1 (90.8;

95.0)

30.6 (25.3;

36.4)

99.4 (98.4;

99.8)

93.3 (89.9;

95.9)

Seroresponse^†‡

96.4 (94.7;

97.6)

82.8 (78.4;

86.7)

97.0 (95.1;

98.3)

88.2 (83.4;

92.0)

hSBA GMT

391 (356;

428)

53 (46; 61)

61 (54; 69)

4 (4; 5)

678 (606;

758)

91 (76; 109)

N=739- 883

N=369-438

N=619

N=288

N=~~523~~540- 651

N=~~233~~250- 305

% ≥1:8

(Seroprotection)‡

98.6 (97.6;

99.3)

92.9 (90.1;

95.1)

97.1 (95.4;

98.3)

61.5 (55.6;

67.1)

99.4 (98.4;

99.8)

99.0 (97.2;

99.8)

Seroresponse^†‡

92.8 (90.7;

94.6)

85.6 (81.6;

89.1)

97.6 (95.9;

98.7)

96.4 (93.3;

98.3)

hSBA GMT

98 (91;

106)

49 (43; 55)

58 (53; 64)

9 (8; 10)

387 (352;

426)

175 (149;

206)

N=701- 861

N=347-423

N=611

N=287

N=523-651

N=233- 295

% ≥1:8

(Seroprotection)^‡

98.3 (97.1;

99.0)

91.7 (88.7;

94.2)

96.2 (94.4;

97.6)

67.9 (62.2;

73.3)

99.1 (98.0;

99.7)

98.6 (96.6;

99.6)

Seroresponse^†‡

88.7 (86.2;

91.0)

81.8 (77.4;

85.8)

96.4 (94.4;

97.8)

92.3 (88.1;

95.4)

hSBA

* Clinical trial identifier NCT03537508

‡Non-inferiority criterion met (lower limit of the 2-sided 95% CI is > -10%)

† Seroresponse rate (primary endpoint) for each serogroup: the proportion of participants with an hSBA pre-vaccination titre <1:8 who achieved a

post-vaccination titre ≥ 1:16, or pre-vaccination titre ≥ 1:8 who achieved a post-vaccination titre at least 4-fold greater than the pre-vaccination titre.

N: number of participants in per-protocol analysis set with valid serology results.

95% CI of the single proportion calculated from the exact binomial method

MET52 (NCT03632720) evaluated the immunogenicity of MenQuadfi in infants following a single dose

at 3 months and a booster dose at 12-13 months of age. The percentages of participants who achieved

seroprotection (hSBA titres ≥1:8) 30 days following administration of MenQuadfi booster dose alone or

co-administered with Bexsero at 12-13 months were 99.4% -100% for all four serogroups. Immunogenicity in infants initiating vaccination from 6 months to less than 12 months of age

MET61 (NCT03691610) compared the immunogenicity of one dose (given at 6-7 months of age) and a

booster dose (given at 12-13 months of age) of MenQuadfi to that of MenACWY-CRM 30 days after

each vaccination. The percentage of participants with hSBA titres ≥ 1:8 (seroprotection rate), hSBA

seroresponse rate, and GMTs are presented in Table 5. Immune non-inferiority, based on seroresponse and seroprotection rates after the booster dose, was demonstrated for MenQuadfi as compared to MenACWY-CRM for all four serogroups.

Table 5: Comparison of bactericidal antibody responses to MenQuadfi and MenACWY-CRM 30days after vaccination with routine infant vaccines at 6-months and a booster dose at 12-13months (study MET61*)

	Post 1st Dose		Pre booster dose		Post booster dose
Endpoint	MenQuadfi (95% CI)	Menveo (95% CI)	MenQuadfi (95% CI)	Menveo (95% CI)	MenQuadfi (95% CI)	Menveo (95% CI)
A	N=108-130	N=111-132	N=103	N=91	N=141-170	N=123-158
% ≥1:8	54.6 (45.7;	37.9 (29.6;	77.7 (68.4;	73.6 (63.3;	95.3 (90.9;	93.0 (87.9;
(Seroprotection)	63.4)	46.7)	85.3)	82.3)	97.9)	96.5)
‡
%	30.6 (22.1;	15.3 (9.2;	-	-	89.4 (83.1;	82.9 (75.1;
Seroresponse^†‡	40.2)	23.4)			93.9)	89.1)
hSBA GMT	8 (7; 10)	5 (4; 7)	20 (15; 27)	15 (11; 20)	184 (143;	119 (90.6;
					237)	157)
C	N=104-127	N=107-133	N=118	N=118	N=134-162	N=126-160
% ≥1:8	96.9 (92.1;	90.2 (83.9;	98.1 (93.2;	69.1 (58.8;	100 (97.7;	98.1 (94.6;
(Seroprotection)	99.1)	94.7)	99.8)	78.3)	100)	99.6)
‡
%	92.3 (85.4;	81.3 (72.6;	-	-	99.3 (95.9;	97.6 (93.2;
Seroresponse^†‡	96.6)	88.2)			100)	99.5)
hSBA GMT	167 (129;	41 (33; 52)	150 (117;	13 (10; 17)	1473	319 (263;
	217)		193)		(1236;	388)
					1756)
W	N=108-134	N=112-134	N=120	N=117	N=143-171	N=127-159
% ≥1:8	38.1 (29.8;	28.4 (20.9;	96.2 (90.6;	50.5 (40.0;	100 (97.9;	95.6 (91.1;
(Seroprotection)	46.8)	36.8)	99.0)	61.1)	100)	98.2)
‡
%	18.5 (11.7;	8.0 (3.7;	-	-	99.3 (96.1;	92.9 (86.9;
Seroresponse^†‡	27.1)	14.7)			100)	96.7)
hSBA GMT	6 (4; 7)	4 (3; 5)	47 (36; 61)	6 (5; 8)	442 (367;	106 (83;
					533)	135)
Y	N=102-125	N=106-128	N=120	N=116	N=140-170	N=128-160
% ≥1:8	60.8 (51.7;	26.6 (19.1;	96.2 (90.6;	54.8 (44.2;	100 (97.9;	97.5 (93.7;
(Seroprotection) ‡	69.4)	35.1)	99.0)	65.2)	100)	99.3)
% Seroresponse^†‡	30.4 (21.7; 40.3)	7.5 (3.3;14.32)	-	-	98.6 (94.9; 99.8)	97.7 (93.3; 99.5)
hSBA GMT	8 (7; 11)	4 (3; 5)	46 (36; 59)	7 (5; 8)	423 (358; 499)	133 (107; 166)

*Clinical trial identifier NCT03691610

N: number of participants in per-protocol analysis set with valid serology results.

‡Non-inferiority criterion met (lower limit of the 2-sided 95% CI is > -10%)

†Seroresponse rate (primary endpoint) for each serogroup: the proportion of participants with an hSBA pre-vaccination titre <1:8 who achieved a post-vaccination titre ≥ 1:16, or pre-vaccination titre ≥ 1:8 who achieved a post-vaccination titre at least 4-fold greater than the pre-vaccination titre.

95% CI of the single proportion calculated from the exact binomial method

Immunogenicity in toddlers 12 to 23 month of age

Immunogenicity in subjects 12 through 23 months of age was evaluated in three clinical studies (MET51

[NCT02955797], MET57 [NCT03205371] and MEQ00065 [NCT03890367]).

MET51 was conducted in subjects who were either meningococcal vaccine naïve or had been primed with monovalent meningococcal C conjugate vaccines in their first year of life (see table 6).

Table 6: Comparison of bactericidal antibody responses to MenQuadfi and MenACWY-TT vaccine 30 days after vaccination of meningococcal vaccine naïve subjects only or combined (naïve + MenC primed) subjects 12 through 23 months of age (study MET51*)

Endpoint by Serogroup

MenQuadfi (95% CI)

Naïve

MenACWY-TT (95% CI)

Naïve

MenQuadfi (95% CI)

Combined (Naïve

+ MenC Primed)

MenACWY-TT (95% CI)

Combined (Naïve

+ MenC Primed)

N=293

N=295

N=490

N=393-394

% ≥1:8

(Seroprotection)**

90.8

(86.9; 93.8)

89.5

(85.4; 92.7)

90.4

(87.4; 92.9)

91.6

(88.4; 94.2)

% Seroresponse

76.8

(71.5; 81.5)

72.5

(67.1; 77.6)

76.5

(72.5; 80.2)

77.1

(72.6; 81.2)

hSBA GMT

28.7

(25.2; 32.6)

28.0

(24.4; 32.1)

29.9

(26.9; 33.2)

34.5

(30.5; 39.0)

N=293

N=295

N=489

N=393-394

% ≥1:8

(Seroprotection)**

99.3

(97.6; 99.9)

81.4

(76.4; 85.6)

99.2

(97.9; 99.8)

85.5

(81.7; 88.9)

% Seroresponse

98.3

(96.1; 99.4)

71.5

(66.0; 76.6)

97.1

(95.2; 98.4)

77.4

(72.9; 81.4)

hSBA GMT

436

(380; 500)

26.4

(22.5; 31.0)

880

(748; 1035)

77.1

(60.7; 98.0)

N=293

N=296

N=489

N=393-394

% ≥1:8

(Seroprotection)**

83.6

(78.9; 87.7)

83.4

(78.7; 87.5)

84.9

(81.4; 87.9)

84.0

(80.0; 87.5)

% Seroresponse

67.6

(61.9; 72.9)

66.6

(60.9; 71.9)

70.8

(66.5; 74.8)

68.4

(63.6; 73.0)

hSBA GMT

22.0

(18.9; 25.5)

16.4

(14.4; 18.6)

24.4

(21.8; 27.5)

17.7

(15.8; 19.8)

N=293

N=296

N=488-490

N=394-395

% ≥1:8

(Seroprotection)**

93.2

(89.7; 95.8)

91.6

(87.8; 94.5)

94.3

(91.8; 96.2)

91.6

(88.5; 94.2)

% Seroresponse

81.9

(77.0; 86.1)

79.1

(74.0; 83.5)

84.8

(81.3; 87.9)

78.9

(74.6; 82.9)

hSBA GMT

38.0

(33.0; 43.9)

32.2

(28.0; 37.0)

41.7

(37.5; 46.5)

31.9

(28.4; 36.0)

* Clinical trial identifier NCT02955797

N: number of subjects in the per-protocol analysis set with valid serology results. The number of subjects varies depending on the

timepoints and serogroup.

95% CI of the single proportion calculated from the exact binomial method.

** Non-inferiority criterion met.

Response in subjects previously vaccinated with MenC conjugate vaccines in their first year of life:

The majority of monovalent meningococcal C conjugate vaccine primed toddlers (12-23 months of age) in study MET51 (NCT02955797) had hSBA titres ≥1:8 in the MenQuadfi group (N=198) (≥ 86.7%) and in MenACWY-TT group (N=99) (≥ 85.7%) at D30 post-vaccination. These toddlers received during their infancy MenC-TT or MenC-CRM vaccines. Post-vaccination seroprotection rates were comparable between MenQuadfi and MenACWY-TT for all serogroups regardless of the priming background.

In MenC-CRM primed subjects the GMTs for serogroup A were lower in the MenQuadfi group (N=49) than in the MenACWY-TT group (N=25) [12.0 (8.23; 17.5) vs 42.2 (25.9; 68.8)]. After administration of MenQuadfi seroprotection rates (hSBA titres ≥1:8) for subjects primed with MenC-CRM were lower but still comparable for serogroups A and W compared with those in the MenACWY-TT group [A: 68.8% (53.7; 81.3) vs 96.0% (79.6; 99.9); W: 68.1% (52.9; 80.9) vs

79.2% (57.8; 92.9)]. The rates for serogroup Y were higher but still comparable with those in the MenACWY-TT group [95.8% (85.7; 99.5) vs 80.0% (59.3; 93.2)]. The rates for serogroup C were comparable in both groups [95.7% (85.5; 99.5) vs 92.0% (74.0; 99.0)]. The clinical relevance of these results is unknown. This aspect might be considered for individuals at high risk for MenA infection who received MenC-CRM vaccine in their first year of life.

MET57 (NCT03205371) was conducted in meningococcal vaccine naïve toddlers 12 through 23 months

of age to assess the immunogenicity of the concomitant administration of MenQuadfi with paediatric

vaccines (MMR+V, DTaP-IPV-HB-Hib or PCV-13). Overall, the post-vaccination hSBA seroprotection

rates in subjects who received MenQuadfi was high for all serogroups (between 88.9% and 100%).

Seroresponse and seroprotection rates for serogroup A were comparable when MenQuadfi was co-administered with PCV-13 and alone (56.1%, [95% CI 48.9; 63.2] and 83.7% [95% CI 77.7; 88.6] vs

71.9% [95%CI 61.8; 80.6] and 90.6% [95%CI 82.9; 95.6]). There were differences in the hSBA GMTs

for serogroup A when MenQuadfi was co-administered with PCV-13 (N=196) compared with MenQuadfi

administered alone (N=96) (24.6 [95%CI 20.2; 30.1] and 49.0 [95%CI 36.8; 65.3]).) The clinical

relevance of these results is unknown but this observation might be taken into consideration for

individuals at high risk for MenA infection and consequently vaccinations with MenQuadfi and PCV13

might be performed separately.

MEQ00065 (NCT03890367) study was conducted in meningococcal vaccine naïve toddlers 12 through

23 months of age to assess the immunogenicity of serogroup C using hSBA and rSBA assays following

administration of a single dose of MenQuadfi compared to MenACWY-TT or to MenC-TT.

Superiority of MenQuadfi was demonstrated in comparison to MenACWY-TT vaccine for the hSBA

seroprotection rate and hSBA and rSBA GMTs to meningococcal serogroup C. Non-inferiority was

demonstrated for the rSBA seroprotection rate to meningococcal serogroup C.

Superiority of MenQuadfi was also demonstrated in comparison to MenC-TT vaccine for the rSBA and

hSBA GMTs to meningococcal serogroup C and non-inferiority was demonstrated for the rSBA and

hSBA seroprotection rates to meningococcal serogroup C (see table 7).

Table 7: Comparison of hSBA and rSBA bactericidal antibody responses for serogroup C to

MenQuadfi, MenACWY-TT and MenC-TT vaccines 30 days after vaccination of meningococcal

vaccine naïve subjects 12 through 23 months of age (study MEQ00065*)

Endpoints	MenQuadfi (95% CI)	MenACWY-TT (95% CI)	MenC-TT (95% CI)	MenQuadfi (95% CI)	MenACWY- TT (95% CI)	MenC-TT (95% CI)
Endpoints	hSBA			rSBA
	N=214	N=211	N= 216	N=213	N=210	N= 215
% ≥1:8 (Seroprotection)	99.5^# § (97.4; 100)	89.1 (84.1; 93.0)	99.5 (97.4; 100)	100¶ (98.3; 100)	94.8 (90.8; 97.4)	100 (98.3; 100)
% Seroresponse	99.5 (97.4; 100)	83.4 (77.7; 88.2)	99.1 (96.7; 99.9)	99.5 (97.4; 100)	92.9 (88.5; 95.9)	99.5 (97.4; 100)
GMTs	515^$ (450; 591)	31,6 ( 26.5; 37.6)	227 (198; 260)	2143¥ (1870; 2456)	315 (252; 395)	1624 (1425; 1850)

* Clinical trial identifier NCT03890367

# superiority of MenQuadfi demonstrated versus MenACWY-TT (hSBA seroprotection rates)

§ non inferiority of MenQuadfi demonstrated versus MenC-TT (hSBA seroprotection rates)

$ superiority of MenQuadfi demonstrated versus MenACWY-TT and MenC-TT (hSBA GMTs)

¶ non inferiority of MenQuadfi demonstrated versus MenACWY-TT and MenC-TT (rSBA seroprotection rates)

¥ superiority of MenQuadfi demonstrated versus MenACWY-TT and MenC-TT (rSBA GMTs)

N = number of subjects in the per-protocol analysis set with valid serology results 95% CI of the single proportion calculated from the exact binomial method

Children 2 through 9 years of age

Immunogenicity in subjects 2 through 9 years of age was evaluated in study MET35 (NCT03077438) (stratified by ages 2 through 5 and 6 through 9 years) comparing seroresponses following administration of either MenQuadfi or MenACWY-CRM.

Overall, for subjects 2 through 9 years of age, immune non-inferiority, based on hSBA seroresponse, was demonstrated for MenQuadfi as compared to MenACWY-CRM for all four serogroups.

Table 8: Comparison of bactericidal antibody responses to MenQuadfi and MenACWY-CRM

30 days after vaccination in meningococcal vaccine naïve subjects 2 through 5 years and 6 through 9 years of age (study MET35*)

2-5 years						6-9 years
Endpoint by Serogroup		MenQuadfi (95% CI)		MenACWY-CRM (95% CI)		MenQuadfi (95% CI)		MenACWY-CRM (95% CI)
A		N=227-228		N=221		N=228		N=237
% ≥1:8 (Seroprotection)		84.6 (79.3; 89.1)		76.5 (70.3; 81.9)		88.2 (83.2; 92.0)		81.9 (76.3; 86.5)
% Seroresponse		52.4 (45.7; 59.1)		44.8 (38.1; 51.6)		58.3 (51.6; 64.8)		50.6 (44.1; 57.2)
hSBA GMT		21.6 (18.2; 25.5)		18.9 (15.5; 23.0)		28.4 (23.9; 33.8)		26.8 (22.0; 32.6)
C		N=229		N=222-223		N=229		N=236
% ≥1:8 (Seroprotection)		97.4 (94.4; 99.0)		64.6 (57.9; 70.8)		98.3 (95.6; 99.5)		69.5 (63.2; 75.3)
% Seroresponse		94.3 (90.5; 96.9)		43.2 (36.6; 50.0)		96.1 (92.7; 98.2)		52.1 (45.5; 58.6)
hSBA GMT		208 (175; 246)		11.9 (9.79; 14.6)		272 (224; 330)		23.7 (18.2; 31.0)
	W		N=229		N=222		N=229		N=237
	% ≥1:8 (Seroprotection)		90.8 (86.3; 94.2)		80.6 (74.8; 85.6)		98.7 (96.2; 99.7)		91.6 (87.3; 94.8)
	% Seroresponse		73.8 (67.6; 79.4)		61.3 (54.5; 67.7)		83.8 (78.4; 88.4)		66.7 (60.3; 72.6)
	hSBA GMT		28.8 (24.6; 33.7)		20.1 (16.7; 24.2)		48.9 (42.5; 56.3)		33.6 (28.2; 40.1)
	Y		N=229		N=222		N=229		N=237
	% ≥1:8 (Seroprotection)		97.8 (95.0; 99.3)		86.9 (81.8; 91.1)		99.1 (96.9; 99.9)		94.5 (90.8; 97.0)
	% Seroresponse		88.2 (83.3; 92.1)		77.0 (70.9; 82.4)		94.8 (91.0; 97.3)		81.4 (75.9; 86.2)
	hSBA GMT		49.8 (43.0; 57.6)		36.1 (29.2; 44.7)		95.1 (80.2; 113)		51.8 (42.5; 63.2)

* Clinical trial identifier NCT03077438

N: number of subjects in the per-protocol analysis set with valid serology results. The number of subjects varies depending on the

timepoints and serogroup.

95% CI of the single proportion calculated from the exact binomial method.

Immunogenicity in children and adolescents 10 through 17 years of age

Immunogenicity in subjects aged 10 through 17 years of age was evaluated in three studies comparing seroresponses following administration of MenQuadfi compared to either MenACWY-CRM (MET50 [NCT02199691]) or MenACWY-DT (MET43[NCT02842853]). or comparing seroprotection following administration of MenQuadfi compared to MenACWY-TT (MEQ00071) [NCT04490018]).

MET50 was conducted in meningococcal vaccine naïve subjects and seroresponse was evaluated following administration with either MenQuadfi alone, MenACWY-CRM alone, MenQuadfi co- administered with Tdap and 4vHPV or Tdap and 4vHPV alone.

Table 9: Comparison of bactericidal antibody responses to MenQuadfi and MenACWY-CRM

30 days after vaccination in meningococcal vaccine naïve subjects 10 through 17 years of age (study MET50*)

Endpoint by Serogroup		MenQuadfi (95% CI)				MenACWY-CRM (95% CI)
A		N=463				N=464
% ≥1:8 (Seroprotection)		93.5		(90.9; 95.6)		82.8		(79.0; 86.1)
% Seroresponse**#		75.6		(71.4; 79.4)		66.4		(61.9; 70.7)
hSBA GMT		44.1		(39.2; 49.6)		35.2		(30.3; 41.0)
C		N=462				N=463
% ≥1:8 (Seroprotection)		98.5		(96.9; 99.4)		76.0		(71.9; 79.8)
% Seroresponse**#		97.2		(95.2; 98.5)		72.6		(68.3; 76.6)
hSBA GMT		387		(329; 456)		51.4		(41.2; 64.2)
W		N=463				N=464
% ≥1:8 (Seroprotection)		99.1		(97.8; 99.8)		90.7		(87.7; 93.2)
% Seroresponse**#		86.2		(82.7; 89.2)		66.6		(62.1; 70.9)
	hSBA GMT		86.9		(77.8; 97.0)		36.0		(31.5; 41.0)
	Y		N=463				N=464
	% ≥1:8 (Seroprotection)		97.2		(95.2; 98.5)		83.2		(79.5; 86.5)
	% Seroresponse**#		97.0		(95.0; 98.3)		80.8		(76.9; 84.3)
	hSBA GMT		75.7		(66.2; 86.5)		27.6		(23.8; 32.1)

* Clinical trial identifier NCT02199691

N: number of subjects in the per-protocol analysis set with valid serology results. 95% CI of the single proportion calculated from the exact binomial method.

** Post-vaccination hSBA titres ≥1:8 for subjects with pre-vaccination hSBA titres < 1:8 or at least a 4-fold increase in hSBA titres from pre to post-vaccination for subjects with pre-vaccination hSBA titres ≥1:8

# Non-inferiority criterion met.

Study MET43 was performed to evaluate the immunogenicity of MenQuadfi compared to MenACWY-DT in children, adolescents and adults (10 through 55 years of age).

Table 10: Comparison of bactericidal antibody responses to MenQuadfi and MenACWY-DT 30 days after vaccination in meningococcal vaccine naïve subjects 10 through 17 years of age (study MET43*)

Endpoint by Serogroup	MenQuadfi (95% CI)		MenACWY-DT (95% CI)
A	N=1,097		N=300
% ≥1:8 (Seroprotection)	96.2	(94.9; 97.2)	89.0	(84.9; 92.3)
% Seroresponse**	74.0	(71.3; 76.6)	55.3	(49.5; 61.0)
hSBA GMT	78	(71.4; 85.2)	44.2	(36.4; 53.7)
C	N=1,097-1,098		N=300
% ≥1:8 (Seroprotection)	98.5	(97.5; 99.1)	74.7	(69.3; 79.5)
% Seroresponse**	95.6	(94.2; 96.8)	53.3	(47.5; 59.1)
hSBA GMT	504	(456; 558)	44.1	(33.7; 57.8)
W	N=1,097		N=300
% ≥1:8 (Seroprotection)	98.3	(97.3; 99.0)	93.7	(90.3; 96.1)
% Seroresponse**	84.5	(82.2; 86.6)	72.0	(66.6; 77.0)
hSBA GMT	97.2	(88.3; 107)	59.2	(49.1; 71.3)
Y	N=1,097		N=300
% ≥1:8 (Seroprotection)	99.1	(98.3; 99.6)	94.3	(91.1; 96.7)
% Seroresponse**	95.6	(94.2; 96.8)	85.7	(81.2; 89.4)
hSBA GMT	208	(189; 228)	80.3	(65.6; 98.2)

* Clinical trial identifier NCT02842853

N: number of subjects in the per-protocol analysis set with valid serology results.The number of subjects varies depending on the timepoints and serogroup.

95% CI of the single proportion calculated from the exact binomial method.

** Non-inferiority criterion met.

MEQ00071 was conducted in subjects who were either meningococcal vaccine naïve or had been primed with MenC vaccines before two years of age. Seroprotection was evaluated 30 days following administration with either MenQuadfi alone, MenACWY‑TT alone, or MenQuadfi co-administrated with Tdap-IPV and 9vHPV.

Table 11: Comparison of bactericidal antibody responses to MenQuadfi and MenACWY-TT 30 days after vaccination in meningococcal vaccine naïve and MenC primed subjects 10 through 17 years of age (study MEQ00071*)

Endpoint by Serogroup	MenQuadfi (95% CI)	MenACWY-TT (95% CI)
A	N=158-159	N=159-160
% ≥1:8 (Seroprotection)**	97.5 (93.7; 99.3)	92.5 (87.3; 96.1)
% Seroresponse	88.0 (81.9; 92.6)	75.5 (68.0; 81.9)
hSBA GMT	78.2 (64.6; 94.7)	56.0 (44.0; 71.2)
C	N=158-159	N=160-161
% ≥1:8 (Seroprotection)**	100 (97.7; 100)	95.0 (90.4; 97.8)
% Seroresponse	99.4 (96.5; 100)	88.8 (82.8; 93.2)
hSBA GMT	2294 (1675; 3142)	619 (411; 931)
W	N=159	N=159
% ≥1:8 (Seroprotection)**	100 (97.7; 100)	98.8 (95.6; 99.8)
% Seroresponse	93.1 (88.0; 96.5)	81.4 (74.5; 87.1)
hSBA GMT	134 (109; 164)	64.6 (52.5; 79.4)
Y	N=158	N=160
% ≥1:8 (Seroprotection)**	99.4 (96.5; 100)	98.1 (94.6; 99.6)
% Seroresponse	98.7 (95.5; 99.8)	88.1 (82.1; 92.7)
hSBA GMT	169 (141; 202)	84.8 (68.3; 105)

* Clinical trial identifier NCT04490018

N: number of subjects in the per-protocol analysis set with valid serology results. The number of subjects varies depending on the timepoints and serogroup.

95% CI of the single proportion calculated from the exact binomial method.

** Non-inferiority criterion met.

In an exploratory analysis in a non-random subset of participants (N=60), the immune response and protection rates were measured 6 and 30 days following co-administration of MenQuadfi with Tdap-IPV and 9vHPV. The proportion of subjects with seroprotection for serogroup A did not increase within 6 days, whereas most of the subjects had seroprotection against serogroups C, W and Y (> 94%). After 30 days, protection rates in this subset were comparable to the full study population reported in table 11.

Response in subjects according to MenC vaccination status

The immunogenicity of serogroup C following administration of a single dose of MenQuadfi compared to a single dose of MenACWY-TT was assessed in both meningococcal vaccine naïve and MenC primed (before two years of age) subjects (MEQ00071). Overall, the post vaccination seroresponse and hSBA GMTs against serogroup C were higher in meningococcal vaccine naive subjects who received MenQuadfi than those who received MenACWY‑TT, with seroprotection rates also trending higher. No differences in antibody response were observed in MenC primed subjects between groups.

Immunogenicity in adults 18 through 55 years of age

Immunogenicity in subjects from 18 through 55 years of age was evaluated in study MET43 (NCT02842853) comparing MenQuadfi to MenACWY-DT.

Table 12: Comparison of bactericidal antibody responses to MenQuadfi and MenACWY-DT 30 days after vaccination in meningococcal vaccine naïve subjects 18 through 55 years of age (study MET43*)

Endpoint by Serogroup	MenQuadfi (95% CI)		MenACWY-DT (95% CI)
A	N=1,406-1,408		N=293
% ≥1:8 (Seroprotection)	93.5	(92.1; 94.8)	88.1	(83.8; 91.5)
% Seroresponse**	73.5	(71.2; 75.8)	53.9	(48.0; 59.7)
hSBA GMT	106	(97.2; 117)	52.3	(42.8; 63.9)
C	N=1,406-1,408		N=293
% ≥1:8 (Seroprotection)	93.5	(92.0; 94.7)	77.8	(72.6; 82.4)
% Seroresponse**	83.4	(81.4; 85.3)	42.3	(36.6; 48.2)
hSBA GMT	234	(210; 261)	37.5	(29.0; 48.5)
W	N=1,408-1,410		N=293
% ≥1:8 (Seroprotection)	94.5	(93.2; 95.7)	80.2	(75.2; 84.6)
% Seroresponse**	77.0	(74.7; 79.2)	50.2	(44.3; 56.0)
hSBA GMT	75.6	(68.7; 83.2)	33.2	(26.3; 42.0)
Y	N=1,408-1,410		N=293
% ≥1:8 (Seroprotection)	98.6	(97.8; 99.1)	81.2	(76.3; 85.5)
% Seroresponse**	88.1	(86.3; 89.8)	60.8	(54.9; 66.4)
hSBA GMT	219	(200; 239)	54.6	(42.3; 70.5)

* Clinical trial identifier NCT02842853

N: number of subjects in the per-protocol analysis set with valid serology results. The number of subjects varies depending on the

timepoints and serogroup.

95% CI of the single proportion calculated from the exact binomial method.

** Non-inferiority criterion met.

Immunogenicity in adults 56 years of age and older

Immunogenicity in adults ≥ 56 years of age (mean 67.1 years, range 56.0 – 97.2 years) was assessed in study MET49 (NCT02842866) comparing the immunogenicity of MenQuadfi to MenACWY polysaccharide vaccine.

Table 13: Comparison of bactericidal antibody responses to MenQuadfi and MenACWY polysaccharide in meningococcal vaccine naïve in subjects 56 years of age and older 30 days after vaccination (study MET49*)

Endpoint by Serogroup		MenQuadfi (95% CI)				MenACWY polysaccharide (95% CI)
A		N=433				N=431
% ≥1:8 (Seroprotection)		89.4		(86.1; 92.1)		84.2		(80.4; 87.5)
% Seroresponse**		58.2		(53.4; 62.9)		42.5		(37.7; 47.3)
hSBA GMT		55.1		(46.8; 65.0)		31.4		(26.9; 36.7)
C		N=433				N=431
% ≥1:8 (Seroprotection)		90.1		(86.9; 92.7)		71.0		(66.5; 75.2)
% Seroresponse**		77.1		(72.9; 81.0)		49.7		(44.8; 54.5)
hSBA GMT		101		(83.8; 123)		24.7		(20.7; 29.5)
W		N=433				N=431
% ≥1:8 (Seroprotection)		77.4		(73.1; 81.2)		63.1		(58.4; 67.7)
	% Seroresponse**		62.6		(57.8; 67.2)		44.8		(40.0; 49.6)
	hSBA GMT		28.1		(23.7; 33.3)		15.5		(13.0; 18.4)
	Y		N=433				N=431
	% ≥1:8 (Seroprotection)		91.7		(88.7; 94.1)		67.7		(63.1; 72.1)
	% Seroresponse**		74.4		(70.0; 78.4)		43.4		(38.7; 48.2)
	hSBA GMT		69.1		(58.7; 81.4)		21.0		(17.4; 25.3)

* Clinical trial identifier NCT02842866

N: number of subjects in the per-protocol analysis set with valid serology results. 95% CI of the single proportion calculated from the exact binomial method.

** Non-inferiority criterion met.

Persistence of immune response and MenQuadfi booster response

Antibody persistence following primary vaccination in toddlers, adolescents and young adults, and older adults was assessed from at least 3 years and up to 7 years after primary vaccination. The immunogenicity of a MenQuadfi booster dose was also assessed.

Persistence of immune response and MenQuadfi booster response in children 4 through 5 years of age

MET62 (NCT03476135) evaluated the antibody persistence of a primary dose, immunogenicity and

safety of a booster dose of MenQuadfi in children 4 through 5 years of age. These children were primed

with a single dose of MenQuadfi or MenACWY-TT 3 years before as part of the phase II study MET54

when they were 12 through 23 months old. The antibody persistence prior to the MenQuadfi booster dose

and the booster immune response were assessed according to the vaccine (MenQuadfi or MenACWY-TT) children had received 3 years ago (see Table 14).

For all serogroups, hSBA GMTs were higher at D30 post-primary dose than at 3 years (3Y) post-primary dose (D0 pre-booster) for MenQuadfi or MenACWY-TT. The 3Y post-primary (D0 pre-booster) GMTs were higher than the pre-primary GMTs, indicative of long-term persistence of immune response.

After the booster dose, seroprotection rates were nearly 100% for all serogroups in children primed with MenQuadfi.

Table 14: Comparison of bactericidal antibody response 30 days after booster vaccination, and persistence in children (4 through 5 years) primed with MenQuadfi or MenACWY-TT 3 years before in study MET54* – (study MET62**)

Endpoint by Serogroup

MenQuadfi Booster in MenQuadfi primed (95% CI)

MenQuadfi Booster in MenACWY-TT primed (95% CI)

MenQuadfi Booster in MenQuadfi primed + MenACWY-TT primed (95% CI)

Persistence^#

N=42

Booster^$

N=40

Persistence^#

N=49

Booster^$

N=44

Persistence^#

N=91

Booster^$

N=84

D30 - Post primary dose

3Y Post-primary dose (D0 - Pre-booster dose)

D30 - Post primary dose

3Y Post-primary dose (D0 - Pre-booster dose)

D30 - Post primary dose

3Y Post-primary dose (D0 - Pre-booster dose)

% ≥1:8 (Seroprotection)

97.6

(87.4; 99.9)

66.7

(50.5; 80.4)

100

(91.2; 100)

89.8

(77.8; 96.6)

83.7

(70.3; 92.7)

100

(92.0; 100)

93.4

(86.2; 97.5)

75.8

(65.7; 84.2)

100

(95.7; 100)

% Seroresponse

100

(91.2; 100)

95.5

(84.5; 99.4)

97.6

(91.7; 99.7)

hSBA GMT

83.3

(63.9; 109)

11.9

(8.11; 17.4)

763

(521; 1117)

49.6

(32.1; 76.7)

14.7

(10.7; 20.2)

659

(427; 1017)

63.0

(48.3; 82.2)

13.3

(10.5; 17.0)

706

(531; 940)

% ≥1:8 (Seroprotection)

100

(91.6; 100)

100

(91.6; 100)

100

(91.2; 100)

87.8

(75.2; 95.4)

57.1

(42.2; 71.2)

100

(92.0; 100)

93.4

(86.2; 97.5)

76.9

(66.9; 85.1)

100

(95.7; 100)

% Seroresponse

95.0

(83.1; 99.4)

100

(92.0; 100)

97.6

(91.7; 99.7)

hSBA GMT

594

(445; 793)

103

(71.7; 149)

5894

(4325; 8031)

29.4

(20.1; 43.1)

11.6

(7.28; 18.3)

1592

(1165; 2174)

118

(79.3; 175)

31.8

(21.9; 46.1)

2969

(2293; 3844)

% ≥1:8 (Seroprotection)

100

(91.6; 100)

97.6

(87.4; 99.9)

97.5

(86.8; 99.9)

95.9

(86.0; 99.5)

83.7

(70.3; 92.7)

100

(92.0; 100)

97.8

(92.3; 99.7)

90.1

(82.1; 95.4)

98.8

(93.5; 100)

% Seroresponse

97.5

(86.8; 99.9)

100

(92.0; 100)

98.8

(93.5; 100)

hSBA GMT

71.8

(53.3; 96.7)

50.0

(35.9; 69.5)

2656

(1601; 4406)

40.1

(30.6; 52.6)

21.2

(14.6; 30.9)

3444

(2387; 4970)

52.5

(42.7; 64.5)

31.5

(24.2; 41.0)

3043

(2248; 4120)

% ≥1:8 (Seroprotection)

100

(91.6; 100)

97.6

(87.4; 99.9)

100

(91.2; 100)

100

(92.7; 100)

89.8

(77.8; 96.6)

100

(92.0; 100)

100

(96.0; 100)

93.4

(86.2; 97.5)

100

(95.7; 100)

% Seroresponse

100

(91.2; 100)

100

(92.0; 100)

100

(95.7; 100)

hSBA GMT

105

(73.9; 149)

32.5

(24.8; 42.7)

2013

(1451; 2792)

75.8

(54.2; 106)

18.2

(13.8; 24.0)

2806

(2066; 3813)

88.1

(69.3; 112)

23.8

(19.4; 29.1)

2396

(1919; 2991)

* Clinical trial identifier MET54 – NCT03205358. The study was conducted in toddlers 12-23 months old.

** Clinical trial identifier MET62 – NCT03476135

$ N calculated using per protocol analysis set (PPAS) with valid serology results; booster dose = D30 MET62.

# N calculated using full analysis set for persistence (FASP) with valid serology results; D30 post-primary dose = D30 MET54, 3Y Post-primary (D0 pre-booster dose) = D0 MET62.

Vaccine seroresponse: titre is <1:8 at baseline with post-vaccination titre ≥1:16 or titre is ≥1:8 at baseline with a ≥4-fold increase at post-vaccination.

95% CI of the single proportion calculated from the exact binomial method.

Persistence of immune response and MenQuadfi booster response in children 6 through 7 years of age

MEQ00073 (NCT04936685) evaluated the antibody persistence of a primary dose, immunogenicity and safety of a booster dose of MenQuadfi in children 6 through 7 years of age who had previously received a primary dose of MenQuadfi 5 years earlier as part of study MET51 when they were 12 through 23 months of age (see Table 12).

For all serogroups, the 5Y post-primary (pre-booster) GMTs were higher than the pre-primary GMTs, indicative of persistence of immune response.

After the booster dose, seroprotection rates were nearly 100% for all serogroups in children primed with MenQuadfi (98.9%, 97.7%, 100%, and 100% for serogroups A, C, W, and Y, respectively).

Table 15: Comparison of bactericidal antibody response 30 days after booster vaccination with MenQuadfi, and persistence in children (6 through 7 years) primed with MenQuadfi 5 years before in study MET51^* – (study MEQ00073^**)

	MenQuadfi Booster in MenQuadfi primed (95% CI)
	Persistence^#		Booster^$ N=88
Endpoint by Serogroup	D30 – Post-primary dose N=208	5Y Post-primary dose (D0 – Pre-booster dose) N=208	Booster^$ N=88
A
% ≥1:8 (Seroprotection)	90.4 (85.5; 94.0)	76.0 (69.6; 81.6)	98.9 (93.8; 100)
% Seroresponse	-	-	93.2 (85.7; 97.5)
hSBA GMT	28.9 (24.5; 34.0)	14.5 (12.0; 17.5)	1143 (820; 1594)
C
% ≥1:8 (Seroprotection)	99.5 (97.4; 100)	85.1 (79.5; 89.6)	97.7 (92.0; 99.7)
% Seroresponse	-	-	97.7 (92.0; 99.7)
hSBA GMT	1315 (1002; 1724)	37.6 (29.8; 47.4)	8933 (6252; 12764)
W
% ≥1:8 (Seroprotection)	83.7 (77.9; 88.4)	84.6 (79.0; 89.2)	100 (95.9; 100)
% Seroresponse	-	-	98.9 (93.8; 100)
hSBA GMT	25.7 (21.3; 31.0)	30.7 (24.9; 37.9)	8656 (6393; 11721)
Y
% ≥1:8 (Seroprotection)	92.3 (87.8; 95.5)	68.8 (62.0; 75.0)	100 (95.9; 100)
% Seroresponse	-	-	98.9 (93.8; 100)
hSBA GMT	41.6 (35.0; 49.6)	12.7 (10.5; 15.4)	3727 (2908; 4776)

*Clinical trial identifier MET51 – NCT02955797. The study was conducted in toddlers 12-23 months old.

**Clinical trial identifier MEQ00073 – NCT04936685

# N calculated using full analysis set for persistence (FASP) with valid serology results; D30 post-primary dose = D30 MET51, 5Y Post-primary dose (D0 pre-booster dose) = D0 MEQ00073.

$ N calculated using per protocol analysis set (PPAS1) with valid serology results; Booster = D30 MEQ00073 5 years after primary vaccination in MET51.

Vaccine seroresponse: titre is <1:8 at baseline with post-vaccination titre ≥1:16 or titre is ≥1:8 at baseline with a ≥4-fold increase at post-vaccination.

95% CI of the single proportion calculated from the exact binomial method.

Response in subjects according to MenC vaccination status before priming with MenQuadfi in MET51

The antibody responses against serogroup C following administration of a booster dose of MenQuadfi were comparable regardless of MenC vaccination status during their first year of life before priming with MenQuadfi 5 years earlier in MET51.

Persistence of immune response and MenQuadfi booster response in adolescents and adults 13 through 26 years of age

MET59 (NCT04084769) evaluated the antibody persistence of a primary dose, immunogenicity and safety of a booster dose of MenQuadfi in adolescents and adults 13 through 26 years of age who had received a single dose of MenQuadfi in study MET50 or MET43 or MenACWY-CRM in study MET50 or outside of Sanofi Pasteur trials 3-6 years prior. The antibody persistence prior to the MenQuadfi booster dose and the booster immune response were assessed according to the vaccine (MenQuadfi or MenACWY-CRM) subjects had received 3-6 years previously (see Table 16).

For all serogroups, hSBA GMTs were higher at D30 post-primary dose than at 3-6 Years (3-6Y) post-primary dose (D0 pre-booster) for MenQuadfi and MenACWY-CRM primed subjects. The 3-6Y post-primary dose (D0 pre-booster) GMTs were higher than the pre-primary GMTs, indicative of long-term persistence of immune response.

After the booster dose, seroprotection rates were nearly 100% for all serogroups in adolescents and adults primed with MenQuadfi.

Table 16: Comparison of bactericidal antibody response 6 and 30 days after booster vaccination, and persistence in adolescents and adults (13 through 26 years) primed with MenQuadfi or MenACWY-CRM 3-6 years before in study MET50*, MET43** or outside of Sanofi Pasteur trials – (study MET59***)

Endpoint by Serogroup	MenQuadfi Booster in MenQuadfi primed (95% CI)				MenQuadfi Booster in MenACWY-CRM primed (95% CI)
	Persistence^{^}		Booster^$		Persistence^{^}		Booster^$
	D30 – Post-primary dose N=376	3-6Y Post-primary dose (D0 – Pre-booster dose) N=379-380	D06 – Post-booster dose N=46	D30 – Post-booster dose N=174	D30 Post-primary dose N=132-133	3-6Y Post-primary dose (D0 – Pre-booster dose) N=140	D06- Post-booster dose N=45	D30 – Post-booster dose N=176
A
% ≥1:8 (Seroprotection)	94.7 (91.9; 96.7)	72.8 (68.0; 77.2)	91.3 (79.2; 97.6)	99.4 (96.8; 100)	81.2 (73.5; 87.5)	71.4 (63.2; 78.7)	95.6 (84.9; 99.5)	99.4 (96.9; 100)
% Seroresponse	-	-	82.6 (68.6; 92.2)	94.8 (90.4; 97.6)	-	-	77.8 (62.9; 88.8)	93.2 (88.4; 96.4)
hSBA GMT	45.2 (39.9; 51.1)	12.5 (11.1; 14.1)	289 (133; 625)	502 (388; 649)	32.8 (25.0; 43.1)	11.6 (9.41; 14.3)	161 (93.0; 280)	399 (318; 502)
C
% ≥1:8 (Seroprotection)	98.1 (96.2; 99.2)	86.3 (82.4; 89.6)	100 (92.3; 100)	100 (97.9; 100)	74.2 (65.9; 81.5)	49.3 (40.7; 57.9)	97.8 (88.2; 99.9)	100 (97.9; 100)
% Seroresponse	-	-	89.1 (76.4; 96.4)	97.1 (93.4; 99.1)	-	-	93.3 (81.7; 98.6)	98.9 (96.0; 99.9)
hSBA GMT	417 (348; 500)	37.5 (31.6; 44.5)	3799 (2504; 5763)	3708 (3146; 4369)	49.7 (32.4; 76.4)	11.0 (8.09; 14.9)	919 (500; 1690)	2533 (2076; 3091)
W
% ≥1:8 (Seroprotection)	100 (99.0; 100)	88.9 (85.3; 91.9)	100 (92.3; 100)	100 (97.9; 100)	93.2 (87.5; 96.9)	76.4 (68.5; 83.2)	100 (92.1; 100)	100 (97.9; 100)
% Seroresponse	-	-	97.8 (88.5; 99.9)	97.7 (94.2; 99.4)	-	-	88.9 (75.9; 96.3)	98.9 (96.0; 99.9)
hSBA GMT	82.7 (73.6; 92.9)	28.8 (25.1; 33.0)	1928 (1187; 3131)	2290 (1934; 2711)	45.1 (34.3; 59.4)	14.9 (11.9; 18.6)	708 (463; 1082)	2574 (2178; 3041)
Y
% ≥1:8 (Seroprotection)	97.9 (95.9; 99.1)	81.8 (77.5; 85.5)	97.8 (88.5; 99.9)	100 (97.9; 100)	88.7 (82.1; 93.5)	52.1 (43.5; 60.7)	100 (92.1; 100)	100 (97.9; 100)
% Seroresponse	-	-	95.7 (85.2; 99.5)	98.9 (95.9; 99.9)	-	-	91.1 (78.8; 97.5)	100 (97.9; 100)
hSBA GMT	91.0 (78.6; 105)	21.8 (18.8; 25.1)	1658 (973; 2826)	2308 (1925; 2767)	36.1 (27.2; 47.8)	8.49 (6.50; 11.1)	800 (467; 1371)	3036 (2547; 3620)

*MET50 – The study was conducted in adolescents (10-17 years of age).

**MET43 – The study was conducted in children, adolescents and adults (10-55 years of age).

***MET59 – NCT04084769

$N calculated using per protocol analysis set (PPAS 1 and 2) with valid serology results; post-booster dose = D06 or D30 of MET59

^N calculated using full analysis set for persistence (FASP) with valid serology results. The number of subjects varies depending on the timepoints and serogroup; post-primary dose = D30 MET50 or MET43, 3-6 Y post-primary dose (pre-booster dose) = D0 MET59.

Vaccine seroresponse: titre is <1:8 at baseline with post-vaccination titre ≥1:16 or titre is ≥1:8 at baseline with a ≥4-fold increase at post-vaccination.

95% CI of the single proportion calculated from the exact binomial method.

Persistence of immune response and MenQuadfi booster response in adults 59 years of age and older

MEQ00066 (NCT04142242) evaluated the antibody persistence of a primary dose, immunogenicity, and safety of a booster dose of MenQuadfi in adults ≥59 years of age who had received a single dose of MenQuadfi or MenACWY-PS ≥3 years previously in study MET49 or MET44.

3 year persistence

The antibody persistence prior to the MenQuadfi booster dose and the booster immune response were assessed according to the vaccine (MenQuadfi or MenACWY-PS) subjects had received 3 years previously in MET49 (Table 17).

For all serogroups, hSBA GMTs were higher at D30 post-primary dose than at 3 Year (3Y) post-primary dose (D0 pre-booster) for both MenQuadfi-primed and MenACWY-PS-primed adults. In addition, for both primed groups, the 3 Year (3Y) post-primary dose (pre-booster) GMTs were higher than the pre-primary GMTs for serogroups C, W and Y (indicative of long-term persistence of immune response for these serogroups) and were comparable for serogroup A.

Table 17: Comparison of bactericidal antibody response 6 and 30 days after booster vaccination, and persistence in adults (≥59 years) primed with MenQuadfi or MenACWY-PS 3 years before in study MET49* – (study MEQ00066#)

Endpoint by Serogroup	MenQuadfi Booster in MenQuadfi primed (95% CI)				MenQuadfi Booster in MenACWY-PS primed (95% CI)
	Persistence^{^}		Booster^$		Persistence^{^}		Booster^$
	D30 – Post-primary dose N=214	3Y Post-primary dose (D0 - Pre-booster dose) N=214	D06 – Post-booster dose N=58	D30 – Post-booster dose N=145	D30 Post-primary dose N=169	3Y Post-primary dose (D0 - Pre-booster dose) N=169	D06 – Post-booster dose N=62	D30 – Post-booster dose N=130
A
% ≥1:8 (Seroprotection)	89.6 (84.7; 93.4)	65.0 (58.2; 71.3)	91.4 (81.0; 97.1)	93.8 (88.5; 97.1)	85.7 (79.5; 90.6)	65.7 (58.0; 72.8)	72.6 (59.8; 83.1)	87.7 (80.8; 92.8)
% Seroresponse	-	-	36.2 (24.0; 49.9)	79.3 (71.8; 85.6)	-	-	8.1 (2.7; 17.8)	60.8 (51.8; 69.2)
hSBA GMT	48.9 (39.0; 61.5)	12.2 (10.2; 14.6)	43.7 (26.5; 71.9)	162 (121; 216)	37.7 (29.3; 48.7)	11.6 (9.53; 14.1)	13.1 (9.60; 17.8)	56.6 (41.5; 77.2)
C
% ≥1:8 (Seroprotection)	88.2 (83.1; 92.2)	73.4 (66.9; 79.2)	98.3 (90.8; 100)	99.3 (96.2; 100)	71.4 (64.0; 78.1)	47.9 (40.2; 55.7)	51.6 (38.6; 64.5)	85.3 (78.0; 90.9)
% Seroresponse	-	-	77.6 (64.7; 87.5)	93.1 (87.7; 96.6)	-	-	8.1 (2.7; 17.8)	55.0 (46.0; 63.8)
hSBA GMT	84.8 (64.0; 112)	17.7 (14.3; 21.9)	206 (126; 339)	638 (496; 820)	26.7 (19.8; 36.0)	8.47 (6.76; 10.6)	11.1 (7.17; 17.1)	56.0 (39.7; 78.9)
W
% ≥1:8 (Seroprotection)	78.8 (72.6; 84.1)	66.8 (60.1; 73.1)	89.7 (78.8; 96.1)	98.6 (95.1; 99.8)	60.1 (52.3; 67.6)	39.6 (32.2; 47.4)	46.8 (34.0; 59.9)	80.8 (72.9; 87.2)
% Seroresponse	-	-	70.7 (57.3; 81.9)	90.3 (84.3; 94.6)	-	-	6.5 (1.8; 15.7)	49.2 (40.4; 58.1)
hSBA GMT	28.0 (22.2; 35.3)	14.2 (11.6; 17.4)	118 (64.0; 216)	419 (317; 553)	14.7 (11.0; 19.8)	6.54 (5.28; 8.11)	9.89 (6.45; 15.2)	31.0 (22.6; 42.6)
Y
% ≥1:8 (Seroprotection)	92.5 (88.0; 95.6)	68.2 (61.5; 74.4)	94.8 (85.6; 98.9)	100 (97.5; 100)	65.5 (57.8; 72.6)	40.8 (33.3; 48.6)	45.2 (32.5; 58.3)	81.5 (73.8; 87.8)
% Seroresponse	-	-	72.4 (59.1; 83.3)	92.4 (86.8; 96.2)	-	-	8.1 (2.7; 17.8)	49.2 (40.4; 58.1)
hSBA GMT	65.3 (51.8; 82.2)	15.3 (12.3; 19.1)	151 (83.4; 274)	566 (433; 740	19.6 (14.4; 26.7)	7.49 (5.72; 9.82)	11.1 (6.31; 19.4)	40.5 (29.0; 56.4)

* Clinical trial identifier: NCT02842866

# Clinical trial identifier: NCT04142242

^N calculated using full analysis set for persistence (FASP) with valid serology results; Post primary dose = D30 of MET49, 3Y post-primary dose (Pre-booster dose) = D0 of MEQ00066

^$N calculated using per protocol analysis Set 2 and 1 (PPAS2 and PPAS1) with valid serology results. Post booster dose = D06 or D30 of MEQ00066

Vaccine seroresponse - titre is < 1:8 at baseline with post-vaccination titre ≥ 1:16 or titre is ≥ 1:8 at baseline with a ≥ 4-fold increase at post-vaccination.

95% CI of the single proportion calculated using the exact binomial method.

5 years persistence

A subset of subjects (N=52) who were assessed for antibody persistence at 3 years and did not receive the booster dose were re-assessed for antibody persistence at 5 years at which time they received a booster dose of MenQuadfi. In MenQuadfi-primed subjects, hSBA GMTs for serogroups C, W and Y 5Y post-primary dose trended higher than the pre-priming GMTs (and were comparable for serogroup A). Following the MenQuadfi booster dose, seroprotection rates were 100% for serogroups A, C, and Y, and 95.0% for serogroup W in subjects primed with MenQuadfi and 87.5%, 62.5%, 87.5% and 68.8% for serogroups A, C, W and Y, respectively, for those primed with MenACWY-PS. Additionally, hSBA GMTs were higher and seroresponse rates were higher or trended higher for all serogroups in subjects primed with MenQuadfi compared to those primed with MenACWY-PS.

6-7 year persistence

The antibody persistence was assessed according to the vaccine (MenQuadfi or MenACWY-PS) subjects had received 6-7 years previously in study MET44 (Table 18).

For all serogroups, hSBA GMTs were higher at D30 post-primary dose than at 6-7 Year (6-7Y) post-primary dose for MenQuadfi-primed adults. The 6-7Y post-primary GMTs were higher than the pre-primary GMTs for serogroup C, W, and Y in MenQuadfi-primed adults, indicative of long-term persistence of immune response for these serogroups, and were comparable for serogroup A.

Table 18: Comparison of bactericidal antibody persistence in adults (≥59 years) primed with MenQuadfi or MenACWY-PS 6-7 years before in MET44^ – (study MEQ00066^#)

	MenQuadfi primed (95% CI)		MenACWY-PS primed (95% CI)
Endpoint by Serogroup	D30 - Post-primary dose$ N=59	6-7Y Post-primary dose# N=59	D30 - Post-primary dose$ N=26	6-7Y Post-primary dose# N=26
A
% ≥1:8 (Seroprotection)	91.4 (81.0; 97.1)	55.9 (42.4; 68.8)	76.9 (56.4; 91.0)	50.0 (29.9; 70.1)
GMT	48.0 (30.6; 75.4)	9.00 (6.44; 12.6)	27.3 (13.8; 54)	9.64 (5.18; 17.9)
C
% ≥1:8 (Seroprotection)	74.1 (61.0; 84.7)	59.3 (45.7; 71.9)	76.9 (56.4; 91.0)	42.3 (23.4; 63.1)
GMT	52.2 (27.4; 99.7)	11.9 (7.67; 18.5)	23.9 (11.9; 48.1)	7.58 (4.11; 14.0)
W
% ≥1:8 (Seroprotection)	75.9 (62.8; 86.1)	66.1 (52.6; 77.9)	73.1 (52.2; 88.4)	38.5 (20.2; 59.4)
GMT	31.2 (18.8; 52.0)	11.9 (7.97; 17.8)	18.8 (10.1; 34.9)	4.95 (3.39; 7.22)
Y
% ≥1:8 (Seroprotection)	81.0 (68.6; 90.1)	59.3 (45.7; 71.9)	73.1 (52.2; 88.4)	46.2 (26.6; 66.6)
GMT	45.8 (26.9; 78.0)	11.2 (7.24; 17.5)	25.9 (12.4; 53.8)	7.19 (4.09; 12.6)

^Clinical trial identifier: NCT01732627

^#Clinical trial identifier: NCT04142242

N: number of subjects in full analysis set for persistence (FASP) with valid serology results.

$ Post primary dose = D30 of MET44

# 6-7Y Post-primary dose = D0 of MEQ00066

95% CI of the single proportion calculated from the exact binomial method.

Booster response in adolescents and adults at least 15 years of age primed with other MenACWY vaccines

Study MET56 (NCT02752906) compared the immunogenicity of a booster dose of MenQuadfi with a booster dose of MenACWY-DT in subjects at least 15 years of age. These subjects were primed with a quadrivalent meningococcal conjugate vaccine (MenACWY-CRM (11.3%) or with MenACWY-DT (86.3%)) 4 to 10 years earlier.

At baseline, hSBA seroprotection and GMT were similar for serogroups A, C, W, and Y.

Table 19: Comparison of bactericidal antibody responses to MenQuadfi and MenACWY-DT 30 days after booster vaccination in subjects at least 15 years of age primed with MenACWY-CRM or MenACWY-DT 4 to 10 years earlier (study MET56*)

Endpoint by Serogroup	MenQuadfi (95% CI)		MenACWY-DT (95% CI)
A	N=384		N=389
% ≥1:8 (Seroprotection)	100.0	(99.0; 100.0)	99.0	(97.4; 99.7)
% Seroresponse**	92.2	(89.0; 94.7)	87.1	(83.4; 90.3)
hSBA GMT	497	(436; 568)	296	(256; 343)
C	N=384		N=389
% ≥1:8 (Seroprotection)	99.5	(98.1; 99.9)	99.0	(97.4; 99.7)
% Seroresponse**	97.1	(94.9; 98.6)	91.8	(88.6; 94.3)
hSBA GMT	2,618	(2,227; 3,078)	599	(504; 711)
W	N=384		N=389
% ≥1:8 (Seroprotection)	100.0	(99.0; 100.0)	99.7	(98.6; 100.0)
% Seroresponse**	98.2	(96.3; 99.3)	90.7	(87.4; 93.4)
hSBA GMT	1,747	(1,508; 2,025)	723	(614; 853)
Y	N=384		N=389
% ≥1:8 (Seroprotection)	99.7	(98.6; 100.0)	99.5	(98.2; 99.9)
% Seroresponse**	97.4	(95.3; 98.7)	95.6	(93.1; 97.4)
hSBA GMT	2,070	(1,807; 2,371)	811	(699; 941)

* Clinical trial identifier NCT02752906

N: number of subjects in the per-protocol analysis set with valid serology results.

95% CI of the single proportion calculated from the exact binomial method.

** Non-inferiority criterion met.

The European Medicines Agency has deferred the obligation to submit the results of studies within one or more subsets of the paediatric population under 12 months of age (see 4.2 for information on paediatric use).

88 (81

; 96

* Clinical trial identifier NCT03890367

# superiority of MenQuadfi demonstrated versus MenACWY-TT (hSBA seroprotection rates)

§ non inferiority of MenQuadfi demonstrated versus MenC-TT (hSBA seroprotection rates)

$ superiority of MenQuadfi demonstrated versus MenACWY-TT and MenC-TT (hSBA GMTs)

¶ non inferiority of MenQuadfi demonstrated versus MenACWY-TT and MenC-TT (rSBA seroprotection rates)

¥ superiority of MenQuadfi demonstrated versus MenACWY-TT and MenC-TT (rSBA GMTs)

N = number of subjects in the per-protocol analysis set with valid serology results 95% CI of the single proportion calculated from the exact binomial method

)

* Clinical trial identifier NCT03890367

# superiority of MenQuadfi demonstrated versus MenACWY-TT (hSBA seroprotection rates)

§ non inferiority of MenQuadfi demonstrated versus MenC-TT (hSBA seroprotection rates)

$ superiority of MenQuadfi demonstrated versus MenACWY-TT and MenC-TT (hSBA GMTs)

¶ non inferiority of MenQuadfi demonstrated versus MenACWY-TT and MenC-TT (rSBA seroprotection rates)

¥ superiority of MenQuadfi demonstrated versus MenACWY-TT and MenC-TT (rSBA GMTs)

N = number of subjects in the per-protocol analysis set with valid serology results 95% CI of the single proportion calculated from the exact binomial metho

41 (36; 46)

44 (40; 48)

10 (9; 11)

296 (268;

327)

186 (158;

219)

5.2. Pharmacokinetic Properties

No pharmacokinetic studies have been performed.

5.3 Preclinical Safety Data

Non-clinical safety data revealed no special risks for humans based on a developmental and reproductive toxicity study in female rabbits.

The administration of MenQuadfi to female rabbits at a full human dose showed no effects on mating performance, female fertility, no teratogenic potential, and no effect on pre- or post-natal development.

6. PHARMACEUTICAL PARTICULARS

6.1 Excipients List

Sodium chloride

Sodium acetate

Water for injections

6.2. Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3. Shelf Life

4 years.

6.4. Special precautions for storage

Store in a refrigerator (2°C – 8°C). Do not freeze.

Stability data indicate that the vaccine components are stable at temperatures up to 25°C for 72 hours. At the end of this period, MenQuadfi should be used or discarded. These data are intended to guide healthcare professionals in case of temporary temperature excursion only.

6.5. Nature and contents of container

Solution in a Type I borosilicate clear glass vial with a 13 mm chlorobutyl stopper and a flip off seal. Pack of 1, 5 or 10 single dose (0.5 mL) vials.

Pack of 1 single dose (0.5 mL) vial co-packaged with 1 single use empty luer-lok syringe (polypropylene) with a plunger-stopper (synthetic elastomer), and 2 separate needles (stainless steel) with needle-shield (polypropylene).

Not all pack sizes may be marketed.

6.6. Special precautions for disposal and other handling

discolouration) prior to administration. In the event of either being observed, discard the vaccine.

Preparation

Pack of 1, 5 or 10 single dose (0.5 mL) vials

Remove the vial flip off seal and using a suitable syringe and needle, withdraw 0.5 mL of solution from the vial, ensuring no air bubbles are present before injection.

Pack of 1 single dose (0.5 mL) vial co-packaged with 1 single use empty syringe and 2 needles

Specific instructions for luer-lok syringe:

To attach the needle to the syringe, gently twist the needle clockwise into the syringe until slight resistance is felt. Before injection, remove the vial flip off seal and withdraw 0.5 mL of solution from the vial, ensuring no air bubbles are present. A new needle should be used to administer the vaccine.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

Sanofi Pasteur 14 Espace Henry Vallée 69007 Lyon France 8. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: May 2025

8. DATE OF REVISION OF THE TEXT

Date of last revision: It will be added upon SFDA approval Version no. CCDSv13_32_ITC FLEX

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