Menveo is indicated for active immunisation of children (from 2 months of age), adolescents and adults to prevent invasive meningococcal disease caused by Neisseria meningitidis groups A, C, W-135 and Y.

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

Posology 

Primary vaccination (see Pharmacodynamic effects):

* According to country specific epidemiology.
 

Booster

Menveo may be given as a booster dose in subjects who have previously received primary vaccination with Menveo, other conjugated meningococcal vaccine or meningococcal unconjugated polysaccharide vaccine. The need for and timing of a booster dose in subjects previously vaccinated with Menveo is to be defined based on national recommendations.

Elderly

There are no data in individuals older than 65 years of age.

There are limited data in individuals aged 56-65 years.

Method of Administration 

Menveo is to be administered as an intramuscular injection, preferably into the anterolateral aspect of the thigh in infants or into the deltoid muscle (upper arm) in children, adolescents and adults.

Separate injection sites must be used if more than one vaccine is being administered at the same time.

For instructions on reconstitution of the medicinal product before administration, see Use and Handling.

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

As with other vaccines, vaccination with Menveo should be postponed in individuals suffering from an acute severe febrile illness. The presence of a minor infection is not a contraindication.

Anxiety‐related reactions, including vasovagal reactions (syncope), hyperventilation or stress‐related reactions may occur in association with vaccination as a psychogenic response to the needle injection (see Adverse Reactions). It is important that procedures are in place to avoid injury from fainting.

Do not administer the vaccine intravascularly, subcutaneously or intradermally.

Menveo will not protect against infections caused by any other serogroups of N. meningitidis not present in the vaccine.

As with any vaccine, a protective immune response may not be elicited in all vaccines (see Pharmacodynamic effects).

In immunocompromised individuals, vaccination may not result in an appropriate protective antibody response. Menveo has not been evaluated in the immunocompromised. Individuals with HIV infection, complement deficiencies and individuals with functional or anatomical asplenia may not mount an immune response to meningococcal group A, C, W-135 and Y conjugate vaccines.

Individuals receiving treatment that inhibits terminal complement activation (for example, eculizumab) remain at increased risk of invasive disease caused by Neisseria meningitidis groups A, C, W-135 and Y even following vaccination with Menveo.

Only applicable to vial-syringe presentation

Latex-sensitive individuals

The tip cap of the syringe may contain natural rubber latex (see Nature and contents of container).

Although the risk for developing allergic latex reactions is very small, healthcare professionals are encouraged to consider the benefit risk prior to administering this vaccine to patients with known history of hypersensitivity to latex.

Menveo can be given concomitantly with meningococcal group B vaccine (Bexsero).

Children from 2 to 23 months of age

Menveo can be given concomitantly with any of the following monovalent or combination vaccines: diphtheria, acellular pertussis, tetanus, Haemophilus influenzae type b (Hib), inactivated polio, hepatitis B (HBV), inactivated hepatitis A, 7-valent and 13-valent pneumococcal conjugate vaccine (PCV7 and PCV13), pentavalent rotavirus, and measles, mumps, rubella and varicella (MMRV). No increase in the reactogenicity or change in the safety profile of the routine vaccines was observed in clinical trials.

No immune interference was observed for the concomitantly administered vaccines with exception of pneumococcal vaccine serotypes 6B and 19A post-dose 3.

No immune interference was observed post-dose 4 for any pneumococcal vaccine serotypes.

Children from 2 to 10 years of age

The safety and immunogenicity of other childhood vaccines when administered concomitantly with Menveo have not been evaluated.

Adolescents from 11 to 18 years of age

Menveo can be given concomitantly with any of the following monovalent or combination vaccines: tetanus, reduced diphtheria and acellular pertussis vaccine (dTpa) and human papillomavirus quadrivalent (Types 6, 11, 16 and 18) recombinant vaccine (HPV).

There was no evidence of increased reactogenicity, change in the safety profile, or impact on the antibody response of the vaccines following co-administration in clinical trials.

The sequential administration of Menveo one month after dTpa resulted in lower immune response for serogroup W-135 as measured by percentage of subjects with seroresponse. The clinical relevance of this observation is however unknown.

Adults

Menveo can be given concomitantly with any of the following monovalent or combination vaccines: hepatitis A and B, yellow fever, typhoid fever (Vi polysaccharide), Japanese encephalitis and rabies.

No change in the safety profile of the vaccines was observed when co-administered with Menveo in clinical trials, and no clinically relevant interference was shown in the antibody response to the vaccines.

Concomitant administration of Menveo and other vaccines than those listed above has not been studied. If Menveo is to be given at the same time as another injectable vaccine, the vaccines should always be administered at different injection sites. 

If a vaccine recipient is undergoing immunosuppressant treatment, the immunological response may be diminished.

Fertility

Animal studies indicate no effects of Menveo on female fertility. Effects on male fertility have not been evaluated in animal studies.

Pregnancy

Insufficient clinical data on exposed pregnancies are available.

Animal studies with Menveo do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/foetal development, parturition or post-natal development (see Non-clinical information).

Menveo should be used during pregnancy only when clearly needed, and the possible advantages outweigh the potential risks for the foetus.

Lactation

Although insufficient clinical data on the use of Menveo during breast-feeding are available, it is unlikely that secreted antibodies in milk would be harmful when ingested by a breastfed infant. Therefore, Menveo may be used during breast feeding.

No studies on the effects of Menveo on the ability to drive and use machines have been performed.

Clinical trial data

Adverse reactions reported are listed according to the following frequencies:

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

Children from 2 to 23 months of age

The safety of Menveo with 4-dose schedule was evaluated in three randomised, controlled multicenter clinical studies in which 8,735 infants 2 months of age at enrolment received Menveo concomitantly with routine paediatric vaccines (see Interactions). A total of 2,864 infants received the routine paediatric vaccines alone.

Three-dose primary series

The safety of Menveo was assessed in 476 infants who completed a 3-dose infant series, including 297 who received doses at 2, 6 and 12 months and 179 who received doses at 2, 4 and 12 months of age.

Two-dose primary series

The safety of Menveo with 2-dose schedule was assessed in 2,180 children immunised between 6 and 23 months of age, in four randomised studies that addressed the safety of Menveo administered concomitantly with routine paediatric vaccines.

One-dose schedule

In three studies, the safety of one dose of Menveo when given concomitantly with routine paediatric vaccines in the second year of life was evaluated in 537 subjects.

Metabolism and nutrition disorders:

Very common: eating disorder

Nervous system disorders:

Very common: persistent crying, sleepiness

Gastrointestinal disorders:

Very common: diarrhoea, vomiting

Skin and subcutaneous tissue disorders:

Common: rash

General disorders and administration site conditions:

Very common: irritability, injection site tenderness, injection site erythema (≤50 mm), injection site induration (≤50 mm)

Common: severe injection site tenderness, fever

Uncommon: injection site erythema (>50 mm), injection site induration (>50 mm)

Children from 2 to 10 years of age

The characterisation of the safety profile of Menveo in children 2 to 10 years of age is based on data from 4 clinical trials in which 3,181 subjects received Menveo. 

Metabolism and nutrition disorders:

Common: eating disorder

Nervous system disorders:

Very common: sleepiness, headache

Gastrointestinal disorders:

Common: nausea, vomiting, diarrhoea

Skin and subcutaneous tissue disorders:

Common: rash

Musculoskeletal and connective tissue disorders:

Common: myalgia, arthralgia

General disorders and administration site conditions:

Very common: irritability, malaise, injection site pain, injection site erythema (≤ 50 mm), injection site induration (≤ 50 mm)

Common: injection site erythema (>50mm), injection site induration (>50mm), chills, fever ≥38^oC

Uncommon: injection site pruritus

Adolescents and adults from 11 to 65 years of age

The characterisation of the safety profile of Menveo in adolescents and adults is based on data from five randomised controlled clinical trials including 6,401 participants (from 11-65 years of age).

Nervous system disorders:

Very common: headache

Uncommon: dizziness

Gastrointestinal disorders:

Very common: nausea

Skin and subcutaneous tissue disorders:

Common: rash

Musculoskeletal and connective tissue disorders

Very common: myalgia

Common: arthralgia

General disorders and administration site conditions:

Very common: injection site pain, injection site erythema (≤50 mm), injection site induration (≤50 mm), malaise

Common: injection site erythema (>50 mm), injection site induration (>50 mm), fever ≥38°C, chills

Uncommon: injection site pruritus

Post-marketing data

Because these events were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or to establish, for all events, a causal relationship to vaccine exposure.

Blood and lymphatic system disorders
Local lymphadenopathy

Immune system disorders

Hypersensitivity including anaphylaxis

Nervous system disorders

Dizziness, syncope, tonic convulsion, febrile convulsion, headache, facial paresis, balance disorder

Eye disorders

Eyelid ptosis

Ear and labyrinth disorders

Hearing impaired, ear pain, vertigo, vestibular disorder

Respiratory, thoracic and mediastinal disorders

Oropharyngeal pain

Skin and subcutaneous tissue disorders

Bullous conditions

Musculoskeletal and connective tissue disorders

Arthralgia, bone pain

General disorders and administration site conditions

Injection site pruritus, pain, erythema, inflammation and swelling, including extensive swelling of the injected limb, fatigue, malaise, pyrexia

Investigations

Alanine aminotransferase increased

Injury and poisoning and procedural complications

Fall, head injury.

To report any side effect(s):

Kingdom of Saudi Arabia

-National Pharmacovigilance centre (NPC)

• Reporting Hotline:19999
• E-mail: npc.drug@sfda.gov.sa
• Website: https://ade.sfda.gov.sa

-GSK - Head Office, Jeddah

• Tel:  +966-12-6536666
• Mobile: +966-56-904-9882
• Email: saudi.safety@gsk.com
• Website: https://gskpro.com/en-sa/
• P.O. Box 55850, Jeddah 21544, Saudi Arabia

For any information about this medicinal product, please contact:

GSK - Head Office, Jeddah

• Tel:  +966-12-6536666
• Mobile: +966-56-904-9882
• Email: gcc.medinfo@gsk.com
• Website: https://gskpro.com/en-sa/ 
• P.O. Box 55850, Jeddah 21544, Saudi Arabia

Insufficient data are available.

ATC code

Pharmacotherapeutic group: Meningococcal vaccines, ATC code: J07AH08.

Pharmacodynamic effects 

Clinical efficacy

The efficacy of Menveo has been inferred by measuring the production of serogroup-specific anti-capsular antibodies with bactericidal activity. Serum bactericidal activity (SBA) was measured using human serum as the source of exogenous complement (hSBA).  The hSBA was the original correlate of protection against meningococcal disease.

Immunogenicity

Immunogenicity was evaluated in randomised, multicenter, active controlled clinical trials that enrolled persons from 2 months through 65 years of age.

Immune responses following a 4-dose infant series (2 months through 16 months of age)

The pre-specified endpoint for immunogenicity of Menveo in infants receiving a 4-dose series at 2, 4, 6 and 12 months of age was the proportion of subjects achieving an hSBA ≥ 1:8, with the lower limit of the 2-sided 95% CI for the point estimate being ≥ 80% of vaccinees for serogroup A, and ≥ 85% of vaccinees for serogroups C, W-135 and Y one month following the final dose. The immunogenicity of Menveo in infants was assessed in two pivotal randomised, controlled, multicenter studies of infants, who received a 4-dose series at 2, 4, 6 and 12 months of age and subjects who received a 4-dose series at 2, 4, 6, and 16 months of age.

In two pivotal trials the pre-defined criteria for immunogenicity were met for all four serogroups A, C, W-135 and Y at one month following completion of a 4-dose series at 2, 4, 6 and 12 months (Table 1).

Table 1: Bactericidal antibody responses following administration of Menveo with routine paediatric vaccines at 2, 4, 6 and 12 or 16 months of age

* Prespecified criteria for adequacy of immune response were met (Study V59P14, US cohort: lower limit (LL) of 95% CI) ≥ 80% for serogroup A and ≥ 85% for serogroups C, W-135, and Y; Study V59_33: LL of the 95% CI > 80% for serogroup A and > 85% for serogroups C, W, and Y).
Serum Bactericidal Assay with exogenous human complement source (hSBA). 

%≥1:8  = proportions of subjects with hSBA ≥ 1:8 against a given serogroup; CI = confidence interval; GMT = geometric mean antibody titre; N = number of infants eligible for inclusion in the Per-Protocol Immunogenicity population for whom serological results were available for the post-dose 3 and post-dose 4 evaluations.

In a separate study performed in Canada in 90 infants receiving Menveo concomitantly with  diphtheria toxoid, acellular pertussis, tetanus toxoid, inactivated polio types 1, 2 and 3, Haemophilus influenzae  type b (Hib), and 7-valent pneumococcal conjugate vaccine, the percentages of subjects with hSBA ≥ 1:8 were 49% for serogroup A, 89% for serogroup C, 92% for serogroup W-135 and 86% for serogroup Y at one month after the second dose of the infant vaccination series (doses administered at 2 and 4 months of age).

Immune responses following a 3-dose infant series (2 months through 12 months of age) (applicable if the three-dose primary infants schedule is included in the country submission)

In study V59_36, children 2 months of age at enrolment were administered either 4 doses at 2, 4, 6 and 12 months of age or 3 doses at 2, 4 and 12 months of age. By one month after the second vaccination (5 months of age), substantial increases in immune responses were seen for all 4 serogroups. The 3-dose series was shown to be non-inferior to the 4-dose series for serogroups C, W-135 and Y at 1 month after the 12 month vaccination.  The hSBA GMTs at 13 months were also similar between the 3-dose and 4-dose groups for serogroups C, W-135 and Y (Table 2). Non-inferiority for serogroup A was not assessed.

Table 2: Bactericidal antibody responses following a 3-dose (2, 4 and 12 months) and a 4-dose infant series of Menveo with routine paediatric vaccines

* Non-inferiority criterion met (the lower limit of the two-sided 95% CI >-10 % for vaccine group differences [3-dose series minus 4-dose series].

In study V59P14, children 2 months of age at enrolment were administered either 3 doses at 2, 6 and 12 months of age or 4 doses at 2, 4, 6 and 18 months of age, and were assessed for immune response at 7 months of age.  Among 284 infants who received doses at 2 and 6 months, 74%, 94%, 99%, 97% had hSBA ≥ 1:8 against serogroups A, C, W-135 and Y, respectively, compared to 89%, 97%, 98%, and 98% of  277 infants who received doses at 2, 4, and 6 months.  Pre-specified non-inferiority criteria were met for serogroups C, W-135, and Y.

Immune responses following a 2-dose series in children 6 months through 23 months of age

The immunogenicity of Menveo was assessed in children, who did not receive the 4-dose series but instead received 2 dose series. Among the per protocol population of 386 subjects, after Menveo administered at 7-9 and at 12 months, the proportions of subjects with hSBA ≥ 1:8 for serogroups A, C, W-135, and Y were respectively: 88% (84-91), 100% (98-100), 98% (96-100), 96% (93-99). 

A 2-dose series was also examined in a study of Latin American children, who received Menveo at 12 and 16 months of age.  Among the per protocol population of 106 subjects, the proportions of subjects with hSBA ≥1:8 for serogroups A, C, W-135 and Y were 97% (92-99), 100% (96-100), 100% (96-100), and 100% (96-100), respectively.

Immunogenicity in children (2-10 years of age)

In the pivotal study V59P20 immunogenicity of Menveo was compared to quadrivalent diphtheria toxoid conjugate meningococcal vaccine (ACWY-D); 1,170 children were vaccinated with Menveo and 1,161 received the comparator vaccine in the per protocol populations.  In two supportive studies V59P8 and V59P10 immunogenicity of Menveo was compared to quadrivalent meningococcal polysaccharide vaccine (ACWY-PS). 

In the pivotal, randomised, observer-blind study V59P20, in which participants were stratified by age (2 through 5 years and 6 through 10 years), the immunogenicity of a single dose of Menveo one month post-vaccination was compared with the single dose of ACWY-D.  In both age groups, non-inferiority of Menveo to ACWY-D for the proportion of subjects with a seroresponse and percentage of subjects with hSBA ≥1:8 was demonstrated for serogroups C, W-135 and Y, but not for serogroup A.  For both age groups (2-5 years and 6-10 years of age), the immune response as measured by hSBA GMTs was non-inferior for all serogroups (Table 3). In addition, the percentage of subjects with a seroresponse, percentage of subjects with hSBA ≥1:8, and GMT levels were statistically higher among Menveo recipients for serogroups W-135 and Y.  GMT levels were also statistically higher among Menveo recipients for serogroup C.

Table 3: Comparison of serum bactericidal antibody responses to Menveo and ACWY-D 1 month after vaccination of subjects 2 through 10 years of age

‡ Seroresponse was defined as: a) post-vaccination hSBA ≥1:8 for subjects with a pre-vaccination hSBA <1:4; or, b) at least 4-fold higher than baseline titres for subjects with a pre-vaccination hSBA ≥1:4.

* Non-inferiority criterion met (the lower limit of the two-sided 95% CI >-10 % for vaccine group differences [Menveo minus ACWY-D] and > 0.5 for ratio of GMTs [Menveo/ACWY-D]).

§ Immune response was statistically higher (the lower limit of the two-sided 95% CI >0% for vaccine group differences or > 1.0 for ratio of GMTs); however the clinical relevance of higher post-vaccination immune responses is not known

The following paragraph can be included when the indication for this age group follows the US label (two doses for all children at continued high risk):

In the same study, a separate group of children, 2 through 5 years of age (N=297) in the per protocol population were immunized with two doses of Menveo, two months apart. The observed seroresponse rates (with 95% CI) at 1 month after the second dose were: 91% (87-94), 98% (95-99), 89% (85-92), and 95% (91-97) for serogroups A, C, W-135 and Y, respectively.  The proportion of subjects with hSBA ≥ 1:8 (95% CI) were 91% (88-94), 99% (97-100), 99% (98-100), and 98% (95-99) for serogroups A, C, W-135 and Y, respectively.  The hSBA GMTs (95% CI) for this group were 64 (51-81), 144 (118-177), 132 (111-157), and 102 (82-126) for serogroups A, C, W-135 and Y, respectively.

In another randomised, observer-blind study (V59P8) US children were immunised with a single dose of either Menveo (N=284) or ACWY-PS (N=285). In the children 2-10 years of age, as well as in each age strata (2-5 and 6-10 years), immune response as measured by percentage of subjects with seroresponse, hSBA≥1:8 and GMTs were not only non-inferior to comparator vaccine ACWY-PS, but all were statistically higher than the comparator for all serogroups and all immune measurements at 1 month post-vaccination (Table 4). 

Table 4: Comparison of serum bactericidal antibody responses to Menveo and ACWY-PS 1 month and 12 months after vaccination of subjects 2 through 10 years of age

‡ Seroresponse was defined as: a) post-vaccination hSBA ≥1:8 for subjects with a pre-vaccination hSBA <1:4; or, b) at least 4-fold higher than baseline titres for subjects with a pre-vaccination hSBA ≥1:4.

* Non-inferiority criterion met (the lower limit of the two-sided 95% CI >-10 % for vaccine group differences [Menveo minus ACWY-PS] and > 0.5 for ratio of GMTs [Menveo/ACWY-PS]).

§ Immune response was statistically higher (the lower limit of the two-sided 95% CI >0% for vaccine group differences or > 1.0 for ratio of GMTs); however the clinical relevance of higher post-vaccination immune responses is not known.

n/a = not applicable

In a randomised, observer-blind study (V59P10) conducted in Argentina, children were immunised with a single dose of either Menveo (N=949) or ACWY-PS (N=551). Immunogenicity was assessed in a subset of 150 subjects in each vaccine group.  The immune response observed in the children 2-10 years of age was very similar to those observed in the V59P8 study shown above:  immune response to Menveo at 1 month post-vaccination, as measured by percentage of subjects with seroresponse, hSBA≥1:8 and GMTs, was non-inferior to ACWY-PS. 

Persistence of immune response and booster response in children (2-10 years of age)

Persistence of immune response 1 year after primary vaccination with Menveo was evaluated in study V59P8. At 1 year post-vaccination, Menveo continued to be statistically higher than ACWY-PS for serogroups A, W-135 and Y, as measured by percentage of subjects with hSBA≥1:8 and GMTs. Menveo was non-inferior on these endpoints for serogroup C (Table 4).

Antibody persistence at 5 years after primary vaccination was assessed in the extension study V59P20E1. There was substantial antibody persistence observed against serogroups C, W and Y, with the percentages of subjects with hSBA ≥ 1:8 being 32% and 56% against serogroup C in subjects 2-5 and 6-10 years of age, respectively, 74% and 80% against serogroup W, and 48% and 53% against serogroup Y.  GMTs were respectively 6.5 and 12 for serogroup C, 19 and 26 for serogroup W, and 8.13 and 10 for serogroup Y. For serogroup A, 14% and 22% of subjects 2-5 and 6-10 years of age, respectively, had hSBA ≥ 1:8 (GMTs 2.95 and 3.73). Levels for all serogroups were higher than those seen in meningococcal vaccine-naïve children of similar ages. The children also received a booster dose of Menveo, 5 years after a single dose primary vaccination. All subjects in both age groups had hSBA ≥ 1:8 across serogroups, with antibody titres several fold higher than seen after the primary vaccination (Table 5).

Table 5: Persistence of immune responses 5 years after primary vaccination with Menveo, and immune responses 1 month after a booster dose among subjects aged 2 ‑ 5 years and 6 ‑10 years at the time of primary vaccination

Immunogenicity in adolescents

In the pivotal study (V59P13), adolescents or adults received either a dose of Menveo (N = 2649) or comparator vaccine (ACWY-D) (N = 875).  Sera were obtained both before vaccination and 1 month after vaccination.

In another study (V59P6) conducted in 524 adolescents, the immunogenicity of Menveo was compared to that of ACWY-PS. 

In the 11-18 year old population of the pivotal study, V59P13, the immunogenicity of a single dose of Menveo one month post-vaccination is compared with the ACWY-D.  Immunogenicity results at one month after Menveo are summarised below in Table 6.

Non-inferiority of Menveo to ACWY-D was demonstrated for all four serogroups using the primary endpoint (hSBA seroresponse). The percentages of subjects with hSBA seroresponse, the percentage of subjects with hSBA ≥ 1:8 and the ratio of GMTs were statistically higher for serogroups A, W-135, and Y in the Menveo group, as compared to the ACWY-D group (Table 6).

Table 6: Serum bactericidal antibody responses following Menveo one month after vaccination among subjects aged 11-18 years

‡ Seroresponse was defined as: a) post-vaccination hSBA ≥1:8 for subjects with a pre-vaccination hSBA <1:4; or, b) at least 4-fold higher than baseline titres for subjects with a pre-vaccination hSBA ≥1:4.

* Non-inferiority criterion for the primary endpoint met (the lower limit of the two-sided 95% CI >-10 % for vaccine group differences [Menveo minus ACWY-D] and > 0.5 for ratio of GMTs [Menveo/ACWY-D]).

§ Immune response was statistically higher (the lower limit of the two-sided 95% CI >0% for vaccine group differences or > 1.0 for ratio of GMTs); however the clinical relevance of higher post-vaccination immune responses is not known.

In the subset of subjects aged 11-18 years who were seronegative at baseline (hSBA < 1:4), the proportion of subjects who achieved a hSBA ≥ 1:8 after a dose of Menveo were as follows:  serogroup A 75% (780/1039); serogroup C 80% (735/923); serogroup W-135 94% (570/609); serogroup Y 81% (510/630).

In the non-inferiority study, V59P6, immunogenicity was assessed among adolescents aged 11-17 years who had been randomised to receive either Menveo or ACWY-PS.  For all four serogroups (A, C, W-135 and Y) Menveo was shown to be non-inferior to ACWY-PS vaccine based on seroresponse, proportions achieving hSBA ≥1:8, and GMTs, and statistically higher based on seroresponse and GMTs.  In addition, Menveo was statistically higher to ACWY-PS for serogroups A, C and Y in the percentage of subjects with post-vaccination hSBA ≥ 1:8 (Table 7).

Table 7: Immunogenicity of one dose of Menveo or ACWY-PS in adolescents, measured at one month post-vaccination

‡ Seroresponse was defined as: a) post-vaccination hSBA ≥1:8 for subjects with a pre-vaccination hSBA <1:4; or, b) at least 4-fold higher than baseline titres for subjects with a pre-vaccination hSBA ≥1:4.

+Difference in proportions for Menveo minus ACWY-PS

† Ratio of GMTs for Menveo to ACWY-PS.

* Non inferiority criterion met (the lower limit of the two-sided 95% CI >-10 % for vaccine group differences [Menveo minus ACWY-PS], >0.5 for ratio of GMTs [Menveo/ACWY-PS])

^§ Immune response was statistically higher (the lower limit of the two-sided 95% CI >0% for vaccine group differences or > 1.0 for ratio of GMTs); however the clinical relevance of higher post-vaccination immune responses is not known.

Persistence of immune response and booster response in adolescents

In study V59P13E1, the persistence of immune responses against serogroups A, C, W-135 and Y was assessed at 21 months, 3 years and 5 years post primary vaccination among subjects aged 11-18 years at the time of vaccination.

The percentages of subjects with hSBA ≥ 1:8 remained constant against serogroups C, W, and Y from 21 months to 5 years post-vaccination in the Menveo group and decreased slightly over time against serogroup A (Table 8).  At 5 years after primary vaccination, there were significantly higher percentages of subjects with hSBA ≥ 1:8 in the Menveo group than in the vaccine-naive control subjects against all the four serogroups.

Table 8: Persistence of immune responses approximately 21 months, 3 years and 5 years after vaccination with Menveo (subjects were aged 11-18 years at the time of vaccination)

A booster dose of Menveo was administered 3 years after primary vaccination with Menveo or ACWY-D. Both groups showed a robust response to the booster dose of Menveo at one month after vaccination (100% of subjects had hSBA ≥ 1:8 across serogroups) and this response largely persisted through 2 years after the booster dose for serogroups C, W and Y (with 87% to 100% of subjects with hSBA ≥ 1:8 across serogroups). A small decline was observed in percentages of subjects with hSBA ≥ 1:8 against serogroup A, although percentages were still high (77% to 79%).

GMTs declined over time as expected but remained between 2- and 8-fold higher than pre-booster values (Table 8).

In study V59P6E1, at one year post-vaccination, the percentage of Menveo recipients with hSBA ≥ 1:8 remained significantly higher compared with ACWY-PS recipients for serogroups C, W-135 and Y, and similar between the two study groups for serogroup A. hSBA GMTs for serogroups W-135 and Y were higher among Menveo recipients. In 5 years post-vaccination, the percentage of Menveo recipients with hSBA ≥ 1:8 remained significantly higher compared with ACWY-PS recipients for serogroups C and Y. Higher hSBA GMTs were observed for serogroups W-135 and Y (Table 9).

Table 9: Persistence of immune responses approximately 12 months and 5 years after vaccination with Menveo and ACWY-PS (subjects were aged 11-18 years at the time of vaccination)

A booster dose of Menveo was administered 5 years after primary vaccination with Menveo or ACWY-PS. At 7 days after the booster dose, 98%-100% of subjects who previously received Menveo and 73%-84% of subjects who previously received ACWY-PS achieved hSBA ≥1:8 against serogroups A, C, W-135 and Y. At one month post-vaccination, the percentages of subjects with hSBA≥1:8 were 98%-100% and 84%-96%, respectively.

A significant increase in the hSBA GMTs against all four serogroups was also observed at 7 and 28 days after the booster dose (Table 10).

Table 10: Response to Booster: bactericidal antibody responses to Menveo booster administered at 3 or 5 years after the primary vaccination with Menveo or ACWY-D or ACWY-PS in subjects aged 11-17 years

Immunogenicity in adults (19-55 years)

In the pivotal immunogenicity trial, V59P13, immune responses to Menveo were assessed among adults aged 19 to 55 years. Results are presented in Table 11. Non-inferiority of Menveo to ACWY-D was demonstrated for all four serogroups using the primary endpoint (hSBA seroresponse) (Table 11).  Both hSBA GMTs and the percentage of subjects with hSBA seroresponse were statistically higher for serogroups C, W-135, and Y among Menveo recipients than in ACWY-D recipients.  The percentage of subjects with hSBA ≥ 1:8 was statistically higher for serogroups C and Y among Menveo recipients, as compared to the corresponding groups in ACWY-D recipients (Table 11).

Table 11: Serum bactericidal antibody responses following Menveo one month after vaccination among subjects aged 19-55 years

‡ Seroresponse was defined as: a) post-vaccination hSBA ≥1:8 for subjects with a pre-vaccination hSBA <1:4; or, b) at least 4-fold higher than baseline titres for subjects with a pre-vaccination hSBA ≥1:4.

* Non-inferiority criterion met (the lower limit of the two-sided 95% CI >-10 % for vaccine group differences [Menveo minus ACWY-D] and > 0.5 for ratio of GMTs [Menveo/ACWY-D]).

^§ Immune response was statistically higher (the lower limit of the two-sided 95% CI >0% for vaccine group differences or > 1.0 for ratio of GMTs); however the clinical relevance of higher post-vaccination immune responses is not known.

In the subset of subjects aged 19-55 years who were seronegative at baseline, the proportion of subjects who achieved a hSBA ≥ 1:8 after a dose of Menveo were as follows: serogroup A 67% (582/875); serogroup C 71% (401/563); serogroup W-135 82% (131/160); serogroup Y 66% (173/263).

The onset of immune response after the primary vaccination with Menveo in healthy subjects 18 through 22 years of age was evaluated in study V59P6E1. At 7 days post-vaccination, 64% of subjects achieved hSBA ≥1:8 against serogroup A and 88% through 90% of subjects had bactericidal antibodies against serogroups C, W-135 and Y.  At one month post-vaccination, 92% through 98% of subjects had hSBA ≥1:8 against serogroups A, C, W-135 and Y. A robust immune response as measured by hSBA GMTs against all serogroups was also observed at 7 days (GMTs 34 through 70) and 28 days (GMTs 79 through 127) after a single dose vaccination.

Immunogenicity in older adults (56-65 years)

The comparative immunogenicity of Menveo vs. ACWY-PS was evaluated in subjects aged 56-65 years, in study V59P17.  The proportion of subjects with hSBA ≥ 1:8 was non-inferior to ACWY-PS for all four serogroups and statistically higher for serogroups A and Y for all endpoints (seroresponse, hSBA ≥ 1:8, and GMT). In addition, statistically higher responses among Menveo recipients were observed for serogroup C GMTs (Table 12). 

Table 12: Immunogenicity of one dose of Menveo or ACWY-PS in adults aged 56-65 years, measured at one month post-vaccination.

‡ Seroresponse was defined as: a) post-vaccination hSBA ≥1:8 for subjects with a pre-vaccination hSBA <1:4; or, b) at least 4-fold higher than baseline titres for subjects with a pre-vaccination hSBA ≥1:4.

* Non-inferiority criterion met (the lower limit of the two-sided 95% CI >-10 % for vaccine group differences [Menveo minus ACWY-PS] and > 0.5 for ratio of GMTs [Menveo/ACWY-PS]).

^§ Immune response was statistically higher (the lower limit of the two-sided 95% CI >0% for vaccine group differences or > 1.0 for ratio of GMTs); however the clinical relevance of higher post-vaccination immune responses is not known.

Evaluation of pharmacokinetic properties is not required for vaccines.

Non-clinical data reveal no special hazard for humans based on animal studies that are appropriate for the safety assessment of vaccines.

Animal toxicology and/or pharmacology 

Menveo was immunogenic in mice and rabbits. In three repeat-dose toxicity studies in rabbits there was no evidence of systemic toxicity and the vaccine was locally well tolerated.

Reproductive Toxicology 

In a reproductive and developmental toxicity study, female rabbits received three intramuscular doses of Menveo before mating and two additional doses during gestation. Each dose administered to rabbits was equivalent to the human dose and, based on body weights, approximately 10 times the human dose. There were no teratogenic effects, and no findings of increased foetal loss, mortality or resorptions, reductions in body weight of foetuses, or other developmental abnormalities in the offspring.

Powder:

Potassium dihydrogen phosphate (5 mm)

Sucrose (12.5 mg)                                                                  

Solution:

Sodium chloride (4.5 mg)                                          

Sodium dihydrogen phosphate monohydrate (2.5 mm)

Disodium phosphate dihydrate (7.5 mm)      

Water for injections (q.b 0.5 ml)

This medicinal product must not be mixed with other medicinal products.

Store in a refrigerator (2°C - 8°C).

Do not freeze.

Keep the container in the outer carton in order to protect from light. After reconstitution, the product should be used immediately. However, chemical and physical stability after reconstitution was demonstrated for 8 hours below 25°C.

Vial-Syringe presentation

• Powder for 1 dose in a vial (type I glass) with a stopper (obutyl rubber)
• Solution for 1 dose in a pre-filled syringe (type I glass) with a tip cap (type I elastomeric closure with natural rubber latex or type II elastomeric closure that has no detectable natural rubber latex).

Pack size of one dose: 1 vial of powder plus 1 pre-filled syringe.

Vial-Vial presentation

• Powder for 1 dose in a vial (type I glass) with a stopper (obutyl rubber)
• Solution for 1 dose in a vial (type I glass) with a stopper (butyl rubber).

Pack size of one dose: 1 vial of powder plus 1 vial of solution or pack size of 5 doses: 5 vials of powder plus 5 vials of solution.

Not all pack sizes may be marketed.

The contents of the two components in the two different containers (MenA powder and MenCWY solution) are to be mixed prior to vaccination providing 1 dose of 0.5 ml.

For vial-syringe presentation:

Menveo must be prepared for administration by reconstituting the powder (in vial) with the solution (in pre-filled syringe).

The components of the vaccine should be visually inspected before and after reconstitution.

Remove the tip cap from the syringe and attach a suitable needle for the withdrawal (21G, 1 ½ inch length or a 21G, 40 mm length). Use the whole contents of the syringe to reconstitute the powder. 

Invert and shake the vial vigorously and then withdraw 0.5 ml of reconstituted product. Please note that it is normal for a small amount of liquid to remain in the vial following withdrawal of the dose.

Following reconstitution, the vaccine is a clear, colourless to light yellow solution, free from visible foreign particles. In the event of any foreign particulate matter and/or variation of physical aspect being observed, do not administer the vaccine.

Prior to injection, change the needle for one suitable for the administration. After reconstitution, the product should be used immediately. However, chemical and physical stability after reconstitution was demonstrated for 8 hours below 25°C.

For vial-vial presentation:

Menveo must be prepared for administration by reconstituting the powder (in vial) with the solution (in vial).

The components of the vaccine should be visually inspected before and after reconstitution.

Using a syringe and a suitable needle (21G, 1 ½ inch length or a 21G, 40 mm length) withdraw the entire content of the vial of solution and inject into the vial of powder to reconstitute the MenA conjugate component.

Invert and shake the vial vigorously and then withdraw 0.5 ml of reconstituted product. Please note that it is normal for a small amount of liquid to remain in the vial following withdrawal of the dose.

Following reconstitution, the vaccine is a clear, colourless to light yellow solution, free from visible foreign particles. In the event of any foreign particulate matter and/or variation of physical aspect being observed, do not administer the vaccine.

Prior to injection, change the needle for one suitable for the administration. Ensure that no air bubbles are present in the syringe before injecting the vaccine.

After reconstitution, the product should be used immediately. However, chemical and physical stability after reconstitution was demonstrated for 8 hours below 25°C.

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

menveo is trademark owned by or licensed to GSK group of companies.

©2023 GSK,all rights reserved

Manufactured by:

- GSK vaccines Srl Bellaria Rosia, Italy

Tel: (39) 0 577 243111

Fax: (39) 0 577 243074

Or alternatively by:

Patheon Italia S.p.A. -

Monza (MB) ,ITALY –20900 iale G.B. Stucchi, 110 ,V