Anaphylaxis
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Leaflet MENQUADFI solution for injection
- Product code:
- W67379001
- Quantity:
- 1
- Indicated for:
- prevention of meningococcal disease
- Route of administration:
- injectable
- Substance:
- group A, C, W and Y conjugated meningococcal vaccine (vaccine)
- ATC
- J07AH08 — Antiinfectives for systemic use | Bacterial vaccines | Meningococcal vaccines
The meningococcal conjugate vaccine for groups A, C, W, and Y is used to prevent infections caused by Neisseria meningitidis, a bacterium that can cause meningitis and septicemia. The vaccine contains capsular polysaccharides from these serogroups, linked to a carrier protein, which stimulates a stronger and longer-lasting immune response.
The vaccine is administered intramuscularly, usually in a single dose, and is recommended for adolescents, individuals traveling to endemic areas, and those at increased risk of infection, such as students living in dormitories or pilgrims traveling to high-risk regions.
Common side effects include pain at the injection site, mild fever, fatigue, and headache. In rare cases, severe allergic reactions may occur.
The meningococcal conjugate vaccine for groups A, C, W, and Y is an essential preventive measure for reducing the incidence of meningococcal diseases and their severe complications, helping to protect public health.
The vaccine is administered intramuscularly, usually in a single dose, and is recommended for adolescents, individuals traveling to endemic areas, and those at increased risk of infection, such as students living in dormitories or pilgrims traveling to high-risk regions.
Common side effects include pain at the injection site, mild fever, fatigue, and headache. In rare cases, severe allergic reactions may occur.
The meningococcal conjugate vaccine for groups A, C, W, and Y is an essential preventive measure for reducing the incidence of meningococcal diseases and their severe complications, helping to protect public health.
General data about MENQUADFI
- Substance:
- group A, C, W and Y conjugated meningococcal vaccine
- Date of latest medicines list:
- 01-09-2026
- Product code:
- W67379001
- Pharmaceutical form:
- solution for injection
- Quantity:
- 1
- Product type:
- Original
- Price:
- 334.73 RON
- Prescription status:
- P-RF — Medicines dispensed with a medical prescription that is retained by the pharmacy and cannot be renewed.
Official documents
- Added to database:
- 27/11/2020
- Source record updated:
- 18/08/2026
Precautions:
Additional monitoring
This medicine is subject to additional monitoring.
Refrigerated storage
Store in the refrigerator as instructed in the leaflet.
Protect from light
Store protected from light.
Contents of the package leaflet for the medicine MENQUADFI solution for injection
Find in leaflet
Leaflet MENQUADFI
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 micrograms1Conjugated 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 againstinvasive 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 of administration
Posology
Primary vaccination:
Primary vaccination:
* Infants starting vaccination from 6 weeks of age: Two doses (each of 0.5 mL) should beadministered with an interval of at least 2 months. An additional primary dose of MenQuadfi maybe considered appropriate for some individuals (see section 4.4).
* Individuals 12 months of age and older: One single dose (0.5 mL) should be administered.
Booster vaccination:
* After completion of the primary immunisation series prior to 12 months of age, a booster doseshould be given in the second year of life (from 12 months of age) at least 2 months after the lastdose (see section 5.1)
* A single 0.5 mL dose of MenQuadfi may be used to boost individuals 12 months of age and olderwho have previously received a meningococcal vaccine containing the same serogroups (seesection 5.1).
* Long-term antibody persistence data following vaccination with MenQuadfi are available up to7 years after vaccination (see sections 4.4 and 5.1).
Paediatric populationData from MenQuadfi given to infants with a history of preterm birth (31 to < 37 weeks of gestationalage) with the same posology as infants born full term are limited. An additional primary dose of
MenQuadfi may be considered appropriate for some individuals with history of preterm birth, see sections4.8 and 5.1.
The safety and immunogenicity of MenQuadfi in infants under 6 weeks of age have not been established.
Method of administrationFor intramuscular injection only, preferably in the deltoid region or anterolateral thigh depending on therecipient'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 previousadministration 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 ofthe 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 withregard to previous vaccination and possible occurrence of undesirable effects) and a clinical examination.
HypersensitivityAs with all injectable vaccines, appropriate medical treatment and supervision should always be readilyavailable in case of an anaphylactic event following administration of the vaccine.
Intercurrent illnessVaccination 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.
SyncopeSyncope (fainting) and other anxiety‐related reactions can occur following or even before any vaccinationas a psychogenic response to the needle injection. Procedures should be in place to prevent falling orinjury and to manage syncope.
Thrombocytopenia and coagulation disordersMenQuadfi should be given with caution to individuals with thrombocytopenia or any coagulationdisorder that would contraindicate intramuscular injection, unless the potential benefit clearly outweighsthe risk of administration.
ProtectionMenQuadfi will only protect against Neisseria meningitidis groups A, C, W, and Y. The vaccine will notprotect 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 theassay (hSBA) has been reported for MenQuadfi and other quadrivalent meningococcal vaccines. Theclinical relevance of this observation is unknown. However, if an individual is expected to be at particularrisk of exposure to serogroup A and received a dose of MenQuadfi more than approximately one yearpreviously, consideration may be given to administering a booster dose.
Lower hSBA geometric mean titres (GMTs) against serogroup A have been observed after a single doseof MenQuadfi was administered to toddlers who previously received serogroup C meningococcalconjugate vaccine (MenC-CRM) during infancy. Nevertheless, seroprotection rates were comparablebetween treatment groups (see section 5.1). The clinical relevance of this observation is unknown. Thisaspect might be considered for individuals at high risk for MenA infection who received MenC-CRMvaccine in their first year of life.
Immune response in infants aged 6 weeks to less than 12 months
Following a 2-dose primary series of MenQuadfi administered at 2 and 4 months of age, lower antibodytitres against serogroup A were observed after the second dose at 4 months when compared with anothervaccine licensed for use in this population (see section 5.1).
Therefore, for infants who are expected to be at increased risk of invasive meningococcal disease due toexposure to serogroup A, consideration may be given to administer a 3-dose primary series at 2, 4, and 6months of age.
Special population
Data from MenQuadfi given to infants with a history of preterm birth (31 to <37 weeks gestational age)are limited. The potential risk of apnoea and the need for respiratory monitoring for 48-72 hours shouldbe considered when administering the primary immunisation series to very premature infants (born ≤ 28weeks of gestation), and particularly for those with a previous history of respiratory immaturity. As thebenefit of vaccination is high in this group of infants, vaccination should not be withheld or delayed.
Immunodeficiency
It may be expected that in patients receiving immunosuppressive treatment or patients withimmunodeficiency, an adequate immune response may not be elicited (see section 4.5). Persons withfamilial complement deficiencies (for example, C5 or C3 deficiencies) and persons receiving treatmentsthat inhibit terminal complement activation (for example, eculizumab) are at increased risk of invasivedisease caused by Neisseria meningitidis groups A, C, W, and Y, even if they develop antibodiesfollowing vaccination with MenQuadfi. No data on immunocompromised patients are available.
Tetanus immunisationImmunisation 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 totetanus toxoid or impact the safety.
Sodium contentThis medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially‘sodium-free’.
4.5 Interaction with other medicinal products and other forms of interaction
Use with other vaccines
Injection sites on separate limbs and separate syringes must be used in the case of concomitantadministration.
In infants, MenQuadfi can be co-administered with combined diphtheria - tetanus - acellular pertussis(DTaP) - inactivated poliovirus (IPV) - hepatitis B (HepB) - Haemophilus influenzae type b (Hib, inwhich the Hib component is conjugated to tetanus protein) vaccine (DTaP-IPV-HepB-Hib), rotavirusvaccine (live attenuated) and with 10-valent pneumococcal conjugate vaccine (PCV10).
In toddlers aged 12-23 months, MenQuadfi can be co-administered with the measles-mumps-rubellavaccine (MMR) and varicella vaccine (V), DTaP vaccines, including combination DTaP vaccines with
IPV, HepB, and Hib such as DTaP-IPV-HepB-Hib (Hib conjugated to tetanus toxoid) vaccine, PCV10,and 13-valent pneumococcal polysaccharide conjugated vaccine (PCV13). When MenQuadfi wasadministered concomitantly with PCV13 in toddlers aged 12-23 months, lower hSBA GMTs on day 30post-dose for serogroup A were observed. The clinical relevance of this observation is unknown. As aprecaution in toddlers initiating MenQuadfi vaccination at 12-23 months of age and who are at high riskfor serogroup A disease, consideration might be given for administration of MenQuadfi and PCV13vaccines separately.
There was no impact on the immune response to MenQuadfi when a meningococcal serogroup B vaccinewas co-administered at 12 months of age and older.
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 IPV (Tdap-IPV), and 4-valent human papillomavirus vaccine (recombinant, adsorbed) (4vHPV) or 9valent 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 PTand lower antibody responses to FHA, PRN and FIM when Tdap vaccine was administered concomitantlywith MenQuadfi and 4vHPV compared to co-administration with 4vHPV vaccine alone (immuneresponse assessed after the full series of HPV was completed). The clinical implications of the observedpertussis antigen responses also observed with other quadrivalent meningococcal conjugate vaccines areunknown.
The co-administration of MenQuadfi with Tdap-IPV and 9vHPV in children and adolescents aged10-17 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 (immuneresponse assessed after the first dose of 9vHPV) compared to when MenQuadfi was given sequentiallywith 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 preferablycontralateral.
Concomitant administration of MenQuadfi and other vaccines than those listed above has not beenstudied.
Use with systemic immunosuppressive medicinal productsIt may be expected that in patients receiving immunosuppressive treatment an adequate immune responsemay 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 notindicate 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 thepotential risks, including those for the foetus.
Breast-feedingIt is unknown whether MenQuadfi is excreted in human milk. MenQuadfi should only be used duringbreast-feeding when the possible advantages outweigh the potential risks.
FertilityA developmental and reproductive toxicity study was performed in female rabbits. There were no effectson 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 adverse reactions mentioned under section 4.8 “Undesirable effects” maytemporarily affect the ability to drive or use machines.
4.8 Undesirable effects
Summary of the safety profile
The safety of MenQuadfi presented in the tables below is based on three clinical datasets:
* For children, adolescents, adults, and older adults, a pooled analysis of data from 4 919 participantswho received a single dose of MenQuadfi either as a primary dose (N = 4 517) or a booster dose(N = 402). This included 498 children aged 2 through 9 years; 2 289 adolescents aged 10 through17 years; 1 684 adults aged 18 through 55 years; 199 older adults aged 56 through 64 years; and249 elderly aged ≥ 65 years. Of these, 392 adolescents received MenQuadfi co-administered with
Tdap and 4vHPV.
* A pooled analysis of 1 389 toddlers aged 12 through 23 months of age who received a single doseof MenQuadfi. Of these, 589 toddlers received MenQuadfi co-administered with MMR+V (N =189), DTaP-IPV-HepB-Hib (N = 200) or PCV13 (N = 200).
* A pooled analysis of data from 6 060 infants initiating vaccination from 6 weeks through 11months of age who received at least one dose of a primary series consisting of one, two or threeprimary doses of MenQuadfi of which 5 373 toddlers received a booster dose from 12 through18 months of age. MenQuadfi was co-administered with routine paediatric vaccines.
Rates of adverse reactions after a booster dose of MenQuadfi in participants from 12 months of age andolder were comparable to those seen in participants who received a primary dose of MenQuadfi.
When MenQuadfi was co-administered with routine paediatric and adolescent vaccines, the safetyprofiles of the vaccines were comparable to those observed when they were given alone or with adifferent meningococcal serogroup A, C, W, Y vaccine, except:
* Overall, rates of adverse reactions were higher in toddlers aged 12-23 months of age who received
PCV13 given concomitantly with MenQuadfi (36.5%) than in toddlers who received PCV13 alone(17.2%).
* Rates of injection site pain at the 9vHPV injection site were higher when children and adolescentsaged 10-17 years of age were given MenQuadfi concomitantly with the first dose of Tdap-IPV(83.6%) compared to when Tdap-IPV and 9vHPV were given without MenQuadfi (67.3%).
* Higher rates and intensity of solicited adverse reactions were observed in participants aged 12 to 13months and 13 to 26 years of age. Higher rates of unsolicited adverse reactions were observed inparticipants aged 12 to 13 months, who received MenQuadfi concomitantly with a meningococcalserogroup B vaccine (MenB), compared to when MenQuadfi was administered alone.
Tabulated list of adverse reactionsThe following adverse reactions, as listed below, have been identified from (1) clinical trials conductedwith MenQuadfi when the vaccine was given alone to participants 2 years of age and older and (2) post-marketing surveillance. The safety profile observed in infants and toddlers aged 6 weeks through23 months is presented in the paediatric population section.
The adverse reactions are listed by MedDRA system organ class and by frequency according to thefollowing 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: Adverse reactions following administration of MenQuadfi from clinical trials and post-marketing surveillance in individuals 2 years of age and older
MedDRA system organ class Frequency Adverse reactions
Blood and lymphatic system Rare Lymphadenopathydisorders
Immune system disorders Very rare Anaphylaxis1
Not known Hypersensitivity1
Nervous system disorders Very common Headache
Uncommon Dizziness
Not known Febrile convulsions1, seizures1
Gastrointestinal disorders Uncommon Vomiting, nausea
Rare Diarrhoea, stomach pain
Skin and subcutaneous tissue Rare Urticaria, pruritus, rashdisorders
Musculoskeletal and Very common Myalgiaconnective tissue disorders
Rare Pain in extremity
General disorders and Very common Malaiseadministration site conditions
Injection site pain
Common Fever
At the injection site: swelling, erythema
Uncommon Fatigue
At the injection site: pruritus, warmth, bruising, rash
Rare Chills, axillary pain
At the injection site: induration
Not known At the injection site: cellulitis11ADR identified from post-marketing reporting
The safety profile of MenQuadfi in children and adolescents 2 through 17 years of age was generallycomparable to that in adults. Injection site erythema and swelling at the MenQuadfi injection site werereported more frequently in children 2 through 9 years of age (very common) than in the older agegroups.
Paediatric population from 6 weeks through 23 months of age
When co-administered with routine paediatric vaccines, the safety profile of MenQuadfi whenadministered as a booster dose in the second year of life was similar to its safety profile in infants from6 weeks through 11 months of age.
The following reactions, as listed below in Table 2, have been reported following administration of
MenQuadfi in infants and toddlers during clinical trials and post-marketing surveillance:
Table 2: Adverse reactions following administration of MenQuadfi from clinical trials and post-marketing surveillance in individuals 6 weeks through 23 months of age
MedDRA System Organ Class Frequency Adverse reactions
Immune system disorder Very rare Anaphylactic reaction1
Not known Hypersensitivity1
Metabolism and nutrition disorders Very common Appetite lost
Psychiatric disorders Very common Irritability
Uncommon Insomnia3
Nervous system disorders Very common Drowsiness
Not known Febrile convulsions1, seizures1
Vascular disorders Rare Flushing
Gastrointestinal disorders Very common Vomiting2
Common Diarrhoea3
Skin and subcutaneous tissue Uncommon Urticaria3, rashdisorder Rare Petechiae, erythema
General disorders and Very common Fever, abnormal cryingadministration site conditions At the injection site: tenderness /pain,erythema, swelling
Common At the injection site: bruising
At the injection site: haemorrhage,
Uncommon induration, rash, warmth, pruritus3
Not known At the injection site: cellulitis11ADR identified from post-marketing reporting2Less frequent in toddlers 12 months through 23 months3Less frequent in infants initiating vaccination at 6 weeks through 11 months of age
Preterm infants
The safety of MenQuadfi was evaluated in 237 infants with a history of preterm birth (31 to <37 weeks ofgestational age) and no material differences in adverse reactions following MenQuadfi were foundbetween these infants and those who were born full term.
Older population
Overall, within 7 days after vaccination with a single dose of MenQuadfi, the same injection site andsystemic adverse reactions were observed in older (≥ 56 years of age) and younger adults (18 through55 years old), but older adults experienced these reactions at lower frequencies; with the exception ofinjection site pruritus, which was more frequent (common) in older adults. These adverse reactions mostlywere mild or moderate in intensity.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allowscontinued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals areasked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
4.9 Overdose
Overdose with MenQuadfi is unlikely due to its presentation as a single dose vial. In the event ofoverdose, 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 actionAnti-capsular meningococcal antibodies protect against meningococcal diseases via complementmediated bactericidal activity.
MenQuadfi induces the production of bactericidal antibodies specific to the capsular polysaccharides of
Neisseria meningitidis serogroups A, C, W, and Y.
ImmunogenicityThe immunogenicity of MenQuadfi has been evaluated in infants (from 6 weeks of age), toddlers,children and adolescents, adults, and older adults when given as a primary vaccination and a boostervaccination. In addition, clinical data on the persistence of antibody response from at least 3 years and upto 7 years after primary vaccination with MenQuadfi are available (described further below).
Primary immunogenicity analyses were conducted by measuring serum bactericidal activity (SBA) usinghuman serum as the source of exogenous complement (hSBA). Rabbit complement (rSBA) data areavailable in subsets in all age groups and generally follow the trends observed with human complement(hSBA) data. In addition, primary immunogenicity analyses were conducted by measuring both hSBAand rSBA for serogroup C in MEQ00065 [NCT03890367].
Immunogenicity in infants initiating vaccination from 6 weeks through 11 months of age
MET58 (NCT03547271) evaluated the immunogenicity of MenQuadfi following two primary dosesgiven to infants in their first year of life and a booster dose from 12 months of age. The first dose wasadministered between 6 and < 12 weeks of age, the second after an interval of at least 2 months, and abooster dose was given at 12 to 18 months of age. The response was compared to the one elicited by
MenACWY-TT. Vaccines were administered concomitantly with routine paediatric vaccines, including
DTaP-IPV-HepB-Hib, PCV10 or PCV13 (with each MenQuadfi dose), and MMR vaccine (with thebooster dose of MenQuadfi).
Non-inferiority, based on seroprotection rates, was demonstrated following the infant series (post-dose 2)of MenQuadfi compared to MenACWY-TT for serogroups C, W, and Y, but not for serogroup A.
Non-inferiority, based on hSBA GMTs, was demonstrated following the MenQuadfi booster dose ascompared to MenACWY-TT for serogroups C, W, and Y with hSBA GMTs being higher for MenQuadfithan those for MenACWY-TT for these serogroups. Non-inferiority of hSBA GMTs was notdemonstrated for serogroup A.
Table 3: Comparison of hSBA bactericidal antibody responses following two doses of MenQuadfior MenACWY-TT vaccines given 2 months apart with the first dose administered to infants from 6to < 12 weeks and following a booster dose at 12-18 months of age (study MET58*)
MenQuadfi MenACWY-TT
Endpoint by D0 - Pre- D30 - Post D0 - Pre- D30 - Post
D30 - Post D30 - Post
Serogroup # booster booster # booster boosterdose 2 dose 2dose$ dose$ dose$ dose$
A N = 507- N = 540 N = 542- N = 504- N = 567 N = 564-508 543 508 567% ≥ 1:8 63.6 (59.2; 33.7 (29.7; 94.7 (92.4; 75.8 (71.8; 46.2 (42.0; 96.5 (94.6;67.8) 37.9) 96.4) 79.5) 50.4) 97.8)(Seroprotection)% Seroresponse^ 57.2 (52.8; - 90.6 (87.8; 70.4 (66.2; - 91.7 (89.1;61.6) 92.9) 74.4) 93.8)hSBA GMT 11.6 (10.3; 4.92 (4.56; 131 (113; 18.9 (16.7; 6.79 (6.16; 189 (165;13.2) 5.31) 151) 21.5) 7.49) 218)
C N = 508- N = 545 N = 545- N = 514- N = 572 N = 573-513 550 521 578% ≥ 1:8 98.8 (97.5; 88.1 (85.1; 99.6 (98.7; 91.9 (89.3; 41.6 (37.5; 95.5 (93.5;(Seroprotection)** 99.6) 90.7) 100) 94.1) 45.8) 97.0)% Seroresponse^ 97.6 (95.9; - 98.7 (97.4; 89.3 (86.3; - 91.3 (88.7;98.8) 99.5) 91.8) 93.5)hSBA GMT& 322 (290; 32.1 (28.5; 565 (505; 73.4 (64.5; 5.91 (5.36; 120 (106;357) 36.2) 632) 83.5) 6.51) 135)
W N = 516- N = 541 N = 545- N = 519- N = 567 N = 572-518 547 523 575% ≥ 1:8 96.5 (94.6; 89.1 (86.2; 99.8 (99.0; 94.5 (92.1; 77.6 (73.9; 99.5 (98.5;(Seroprotection)** 97.9) 91.6) 100) 96.3) 81.0) 99.9)% Seroresponse^ 95.7 (93.6; - 99.4 (98.4; 93.3 (90.7; - 98.4 (97.0;97.3) 99.9) 95.3) 99.3)hSBA GMT& 66.1 (59.6; 32.4 (29.0; 423 (382; 47.2 (42.6; 16.2 (14.6; 275 (247;73.2) 36.2) 468) 52.3) 17.9) 305)
Y N = 513- N = 545 N = 551- N = 517- N = 572 N = 575-516 554 523 579% ≥ 1:8 96.5 (94.5; 87.9 (84.9; 100 (99.3; 93.5 (91.0; 69.6 (65.6; 99.8 (99.0;(Seroprotection)** 97.9) 90.5) 100) 95.5) 73.3) 100)% Seroresponse^ 93.8 (91.3; - 98.7 (97.4; 90.3 (87.4; - 96.9 (95.1;95.7) 99.5) 92.7) 98.1)hSBA GMT& 44.7 (40.6; 23.4 (21.3; 285 (260; 32.8 (29.8; 11.1 (10.1; 160 (145;49.1) 25.8) 313) 36.2) 12.2) 177)
* Clinical trial identifier NCT03547271
** Non-inferiority criterion met for post dose 2^ Post-hoc analysis non-inferiority criterion met for post booster dose& Non-inferiority criterion met for post booster dose# N calculated using per protocol analysis set 1 with valid serology results; D30 Post dose 2 = 30 daysfollowing the infant series (post-dose 2).
$ N calculated using per protocol analysis set 2 with valid serology results; D0 Pre-booster dose = Beforethe booster dose was administered, D30 Post booster dose = 30 days following the booster dose.
Vaccine seroresponse is defined as a participant with a pre-vaccination (at D0 before the 2-monthvaccination) titre < 1:8, the post-vaccination titre must be ≥ 1:16; for a participant with a pre-vaccination(at D0 before the 2 month vaccination) titre ≥ 1:8, the post-vaccination titre must be at least 4-fold greaterthan the pre-vaccination titre.
In study MET58, immunogenicity of 3 primary doses administered at 2, 4, and 6 months of age wasevaluated in a group of infants (N=90). Thirty days after the third dose was given at 6 months of age, theproportion of participants with an hSBA titre ≥1:8 were 81.8% (95% CI: 72.2; 89.2) for serogroup A and98.9% (95% CI: 94.0; 100) for serogroups C, W, and Y. The percentages of participants with hSBA titres≥ 1:8 increased from pre- to post-booster vaccination from 52.8% (95% CI: 41.9;63.5) to 82.0% (95% CI:
72.5;89.4) for serogroup A, 92.1% (95% CI: 84.5;96.8) to 100% (95% CI: 95.8;100) for serogroup C, 100%(95% CI: 96.0;100) to 100% (95% CI: 95.8;100) for serogroup W, and 100% (95% CI: 96.0;100) to 100%(95% CI: 95.9;100) for serogroup Y.
Immunogenicity in toddlers 12 to 23 months of age
Immunogenicity in toddlers 12 through 23 months of age was evaluated in three clinical trials (MET51[NCT02955797], MET57 [NCT03205371] and MEQ00065 [NCT03890367]).
MET51 was conducted in toddlers who were either meningococcal vaccine-naïve or had been primedwith monovalent meningococcal C conjugate vaccines in their first year of life (see Table 4).
Table 4: Comparison of bactericidal antibody responses to MenQuadfi and MenACWY-TT vaccine30 days after vaccination of meningococcal vaccine-naïve toddlers only or combined (naïve + MenCprimed) toddlers 12 through 23 months of age (study MET51*)
Endpoint by MenQuadfi MenACWY-TT MenQuadfi MenACWY-TT
Serogroup (95% CI) (95% CI) (95% CI) (95% CI)
Naïve Naïve Combined (Naïve Combined (Naïve+ MenC Primed) + MenC Primed)
A N = 293 N = 295 N = 490 N = 393-394% ≥ 1:8 90.8 89.5 90.4 91.6(Seroprotection)** (86.9; 93.8) (85.4; 92.7) (87.4; 92.9) (88.4; 94.2)% Seroresponse 76.8 72.5 76.5 77.1(71.5; 81.5) (67.1; 77.6) (72.5; 80.2) (72.6; 81.2)hSBA GMT 28.7 28.0 29.9 34.5(25.2; 32.6) (24.4; 32.1) (26.9; 33.2) (30.5; 39.0)
C N = 293 N = 295 N = 489 N = 393-394% ≥ 1:8 99.3 81.4 99.2 85.5(Seroprotection)** (97.6; 99.9) (76.4; 85.6) (97.9; 99.8) (81.7; 88.9)% Seroresponse 98.3 71.5 97.1 77.4(96.1; 99.4) (66.0; 76.6) (95.2; 98.4) (72.9; 81.4)hSBA GMT 436 26.4 880 77.1(380; 500) (22.5; 31.0) (748; 1 035) (60.7; 98.0)
W N = 293 N = 296 N = 489 N = 393-394% ≥ 1:8 83.6 83.4 84.9 84.0(Seroprotection)** (78.9; 87.7) (78.7; 87.5) (81.4; 87.9) (80.0; 87.5)% Seroresponse 67.6 66.6 70.8 68.4(61.9; 72.9) (60.9; 71.9) (66.5; 74.8) (63.6; 73.0)hSBA GMT 22.0 16.4 24.4 17.7(18.9; 25.5) (14.4; 18.6) (21.8; 27.5) (15.8; 19.8)
Y N = 293 N = 296 N = 488-490 N = 394-395% ≥ 1:8 93.2 91.6 94.3 91.6(Seroprotection)** (89.7; 95.8) (87.8; 94.5) (91.8; 96.2) (88.5; 94.2)% Seroresponse 81.9 79.1 84.8 78.9(77.0; 86.1) (74.0; 83.5) (81.3; 87.9) (74.6; 82.9)hSBA GMT 38.0 32.2 41.7 31.9(33.0; 43.9) (28.0; 37.0) (37.5; 46.5) (28.4; 36.0)
* Clinical trial identifier NCT02955797
N: number of participants in the per-protocol analysis set with valid serology results. The numberof participants 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 toddlers previously vaccinated with MenC conjugate vaccines in their first year of life
The majority of monovalent meningococcal C conjugate vaccine primed toddlers (12 through 23 monthsof 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 toddlersreceived during their infancy MenC-TT or MenC-CRM vaccines. Post-vaccination seroprotection rateswere comparable between MenQuadfi and MenACWY-TT for all serogroups regardless of the primingbackground.
In MenC-CRM primed toddlers, the GMTs for serogroup A were lower in the MenQuadfi group (N = 49)than in the MenACWY-TT group (N = 25) (12.0, 95% CI: 8.23; 17.5) vs 42.2 (95% CI: 25.9; 68.8). Afteradministration of either MenQuadfi or MenACWY-TT, rates of seroprotection for MenC-CRM-primedtoddlers were 68.8% (95% CI: 53.7; 81.3) vs 96.0% (95% CI: 79.6; 99.9) for serogroup A; 95.7% (95%
CI: 85.5; 99.5) vs. 92.0% (95% CI: 74.0; 99.0) for serogroup C; 68.1% (95% CI: 52.9; 80.9) vs 79.2%(95% CI: 57.8; 93.2) for serogroup W and 95.8% (95% CI: 85.7; 99.5) vs 80.0% (95% CI: 59.3; 93.2) forserogroup Y, respectively. The clinical relevance of these results is unknown. This aspect might beconsidered for individuals at high risk for MenA infection who received MenC-CRM vaccine in their firstyear of life.
MET57 (NCT03205371) was conducted in meningococcal vaccine-naïve toddlers 12 through 23 monthsof age to assess the immunogenicity of the concomitant administration of MenQuadfi with paediatricvaccines (MMR+V, DTaP-IPV-HepB-Hib or PCV13). Overall, the post-vaccination hSBA seroprotectionrates in participants who received MenQuadfi were 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] vs71.9% [95%CI: 61.8; 80.6] and 90.6% [95%CI: 82.9; 95.6]). There were differences in the hSBA GMTsfor 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). Theclinical relevance of these results is unknown, but this observation might be taken into consideration forindividuals at high risk for MenA infection and consequently vaccinations with MenQuadfi and PCV13might be performed separately.
MEQ00065 (NCT03890367) study was conducted in meningococcal vaccine-naïve toddlers 12 through23 months of age to assess the immunogenicity of serogroup C using hSBA and rSBA assays followingadministration 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 hSBAseroprotection rate and hSBA and rSBA GMTs to meningococcal serogroup C. Non-inferiority wasdemonstrated for the rSBA seroprotection rate to meningococcal serogroup C.
Superiority of MenQuadfi was also demonstrated in comparison to MenC-TT vaccine for the rSBA andhSBA GMTs to meningococcal serogroup C and non-inferiority was demonstrated for the rSBA andhSBA seroprotection rates to meningococcal serogroup C (see Table 5).
Table 5: Comparison of hSBA and rSBA bactericidal antibody responses for serogroup C to
MenQuadfi, MenACWY-TT and MenC-TT vaccines 30 days after vaccination of meningococcalvaccine-naïve toddlers 12 through 23 months of age (study MEQ00065*)
MenACWY- MenC- MenACWY- MenC-
MenQuadfi MenQuadfi
TT (95% TT (95% TT (95% TT (95%
Endpoints (95% CI) (95% CI)
CI) CI) CI) CI)hSBA rSBA
N = 214 N = 211 N = 216 N = 213 N = 210 N = 21599.5 100% ≥ 1:8 99.5# § 89.1 100¶ 94.8(97.4; (98.3;(Seroprotection) (97.4; 100) (84.1; 93.0) (98.3; 100) (90.8; 97.4)100) 100)99.1 99.599.5 83.4 99.5 92.9% Seroresponse (96.7; (97.4;(97.4; 100) (77.7; 88.2) (97.4; 100) (88.5; 95.9)99.9) 100)¥515$ 227 2 143 1 62431.6 315
GMTs (198; (1 870; (1 425;(450; 591) ( 26.5; 37.6) (252; 395)260) 2 456) 1 850)
* 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 seroprotectionrates)¥ superiority of MenQuadfi demonstrated versus MenACWY-TT and MenC-TT (rSBA GMTs)
N: number of participants in the per-protocol analysis set with valid serology results95% CI of the single proportion calculated from the exact binomial method
Immunogenicity in children 2 through 9 years of age
Immunogenicity in children 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 administrationof either MenQuadfi or MenACWY-CRM.
Overall, for children 2 through 9 years of age, immune non-inferiority, based on hSBA seroresponse, wasdemonstrated for MenQuadfi as compared to MenACWY-CRM for all four serogroups.
Table 6: Comparison of bactericidal antibody responses to MenQuadfi and MenACWY-CRM30 days after vaccination in meningococcal vaccine-naïve children 2 through 5 years and 6 through9 years of age (study MET35*)2-5 years of age 6-9 years of age
Endpoint by MenQuadfi MenACWY-CRM MenQuadfi MenACWY-CRM
Serogroup (95% CI) (95% CI) (95% CI) (95% CI)
A N = 227-228 N = 221 N = 228 N = 237% ≥ 1:8 84.6 76.5 88.2 81.9(Seroprotection) (79.3; 89.1) (70.3; 81.9) (83.2; 92.0) (76.3; 86.5)% Seroresponse 52.4 44.8 58.3 50.6(45.7; 59.1) (38.1; 51.6) (51.6; 64.8) (44.1; 57.2)hSBA GMT 21.6 18.9 28.4 26.8(18.2; 25.5) (15.5; 23.0) (23.9; 33.8) (22.0; 32.6)
C N = 229 N = 222-223 N = 229 N = 236% ≥ 1:8 97.4 64.6 98.3 69.5(Seroprotection) (94.4; 99.0) (57.9; 70.8) (95.6; 99.5) (63.2; 75.3)% Seroresponse 94.3 43.2 96.1 52.1(90.5; 96.9) (36.6; 50.0) (92.7; 98.2) (45.5; 58.6)hSBA GMT 208 11.9 272 23.7(175; 246) (9.79; 14.6) (224; 330) (18.2; 31.0)
W N = 229 N = 222 N = 229 N = 237% ≥ 1:8 90.8 80.6 98.7 91.6(Seroprotection) (86.3; 94.2) (74.8; 85.6) (96.2; 99.7) (87.3; 94.8)% Seroresponse 73.8 61.3 83.8 66.7(67.6; 79.4) (54.5; 67.7) (78.4; 88.4) (60.3; 72.6)hSBA GMT 28.8 20.1 48.9 33.6(24.6; 33.7) (16.7; 24.2) (42.5; 56.3) (28.2; 40.1)
Y N = 229 N = 222 N = 229 N = 237% ≥ 1:8 97.8 86.9 99.1 94.5(Seroprotection) (95.0; 99.3) (81.8; 91.1) (96.9; 99.9) (90.8; 97.0)% Seroresponse 88.2 77.0 94.8 81.4(83.3; 92.1) (70.9; 82.4) (91.0; 97.3) (75.9; 86.2)hSBA GMT 49.8 36.1 95.1 51.8(43.0; 57.6) (29.2; 44.7) (80.2; 113) (42.5; 63.2)
* Clinical trial identifier NCT03077438
N: number of participants in the per-protocol analysis set with valid serology results. The number ofparticipants 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
MET50 (NCT02199691) was conducted in meningococcal vaccine-naïve participants and the immuneresponse was evaluated following administration with either MenQuadfi alone, MenACWY-CRM alone,
MenQuadfi co-administered with Tdap and 4vHPV, or Tdap and 4vHPV alone.
MET43 (NCT02842853) was performed to evaluate the immunogenicity of MenQuadfi compared to
MenACWY-DT in children and adolescents (10 through 17 years of age).
Table 7: Comparison of bactericidal antibody responses to MenQuadfi and MenACWY-CRM or
MenACWY-DT 30 days after vaccination in meningococcal vaccine-naïve participants 10 through17 years of age (study MET50* and MET43*)
MET50 MET43
Endpoint by MenQuadfi MenACWY-CRM MenQuadfi MenACWY-DT
Serogroup
A N = 463 N = 464 N = 1 097 N = 300% ≥ 1:8 93.5 (90.9; 95.6) 82.8 (79.0; 86.1) 96.2 (94.9; 97.2) 89.0 (84.9; 92.3)(Seroprotection)% Seroresponse**# 75.6 (71.4; 79.4) 66.4 (61.9; 70.7) 74.0 (71.3; 76.6) 55.3 (49.5; 61.0)hSBA GMT 44.1 (39.2; 49.6) 35.2 (30.3; 41.0) 78 (71.4; 85.2) 44.2 (36.4; 53.7)
C N = 462 N = 463 N = 1 097-1 098 N = 300% ≥ 1:8 98.5 (96.9; 99.4) 76.0 (71.9; 79.8) 98.5 (97.5; 99.1) 74.7 (69.3; 79.5)(Seroprotection)% Seroresponse**# 97.2 (95.2; 98.5) 72.6 (68.3; 76.6) 95.6 (94.2; 96.8) 53.3 (47.5; 59.1)hSBA GMT 387 (329; 456) 51.4 (41.2; 64.2) 504 (456; 558) 44.1 (33.7; 57.8)
W N = 463 N = 464 N = 1,097 N = 300% ≥ 1:8 99.1 (97.8; 99.8) 90.7 (87.7; 93.2) 98.3 (97.3; 99.0) 93.7 (90.3; 96.1)(Seroprotection)% Seroresponse**# 86.2 (82.7; 89.2) 66.6 (62.1; 70.9) 84.5 (82.2; 86.6) 72.0 (66.6; 77.0)hSBA GMT 86.9 (77.8; 97.0) 36.0 (31.5; 41.0) 97.2 (88.3; 107) 59.2 (49.1; 71.3)
Y N = 463 N = 464 N = 1,097 N = 300% ≥ 1:8 97.2 (95.2; 98.5) 83.2 (79.5; 86.5) 99.1 (98.3; 99.6) 94.3 (91.1; 96.7)(Seroprotection)% Seroresponse**# 97.0 (95.0; 98.3) 80.8 (76.9; 84.3) 95.6 (94.2; 96.8) 85.7 (81.2; 89.4)hSBA GMT 75.7 (66.2; 86.5) 27.6 (23.8; 32.1) 208 (189; 228) 80.3 (65.6; 98.2)
* Clinical trial identifier NCT02199691 (MET50) and NCT02842853 (MET43)
N: number of participants 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 participants with pre-vaccination hSBA titres < 1:8 or at least a4-fold increase in hSBA titres from pre to post-vaccination for participants with pre-vaccination hSBAtitres ≥1:8# Non-inferiority criterion met.
MEQ00071 (NCT04490018) was conducted in children and adolescents who were either meningococcalvaccine-naïve or had been primed with MenC vaccines (before two years of age) to evaluate the immuneresponse of MenQuadfi alone, MenACWYTT alone, or MenQuadfi co-administrated with Tdap-IPV and9vHPV.
Table 8: Comparison of bactericidal antibody responses to MenQuadfi and MenACWY-TT 30 daysafter vaccination in meningococcal vaccine-naïve and MenC primed children and adolescents 10through 17 years of age (study MEQ00071*)
Endpoint by Serogroup MenQuadfi MenACWY-TT(95% CI) (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 2 294 (1 675; 3 142) 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 participants in the per-protocol analysis set with valid serology results. The number ofparticipants 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 andprotection rates were measured 6 and 30 days following co-administration of MenQuadfi with Tdap-IPVand 9vHPV. The proportion of participants with seroprotection for serogroup A did not increase within6 days, whereas most of the participants had seroprotection against serogroups C, W and Y (> 94%).
After 30 days, protection rates in this subset were comparable to the full trial population reported in table8.
Response in participants according to MenC vaccination status
The post vaccination seroresponse and hSBA GMTs against serogroup C were higher in meningococcalvaccine-naïveparticipants who received MenQuadfi than those who received MenACWY-TT, withseroprotection rates also trending higher. No differences in antibody response were observed in MenCprimed participants between groups.
Immunogenicity in adults 18 through 55 years of age
MET43 (NCT02842853) also evaluated the immunogenicity of MenQuadfi compared to MenACWY-DTin adults aged 18 through 55 years of age.
Table 9: Comparison of bactericidal antibody responses to MenQuadfi and MenACWY-DT 30 daysafter vaccination in meningococcal vaccine-naïve adults 18 through 55 years of age (study MET43*)
Endpoint by Serogroup MenQuadfi MenACWY-DT (95% CI)(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 participants in the per-protocol analysis set with valid serology results. The numberof participants 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 instudy MET49 (NCT02842866) comparing the immunogenicity of MenQuadfi to MenACWYpolysaccharide vaccine.
Table 10: Comparison of bactericidal antibody responses to MenQuadfi and MenACWYpolysaccharide in meningococcal vaccine-naïve in adults 56 years of age and older 30 days aftervaccination (study MET49*)
Endpoint by Serogroup MenQuadfi MenACWY polysaccharide(95% CI) (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)
Endpoint by Serogroup MenQuadfi MenACWY polysaccharide(95% CI) (95% CI)% 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 participants 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 in children 4 through 5 years of age
MET62 (NCT03476135) evaluated the antibody persistence of a primary dose, immunogenicity andsafety of a booster dose of MenQuadfi in children 4 through 5 years of age. These children were primedwith a single dose of MenQuadfi or MenACWY-TT 3 years before as part of the phase II study MET54when they were 12 through 23 months old. The antibody persistence prior to the MenQuadfi booster doseand the booster immune response were assessed according to the vaccine (MenQuadfi or MenACWY-TT)children had received 3 years ago (see Table 11).
For all serogroups, the 3Y post-primary (D0 pre-booster) GMTs were higher than the pre-primary GMTs,indicative of long-term persistence of immune response.
Table 11: Comparison of bactericidal antibody response 30 days after booster vaccination, andpersistence in children (4 through 5 years) primed with MenQuadfi or MenACWY - TT 3 yearsbefore in study MET54* - (study MET62**)
Endpoint by MenQuadfi Booster in MenQuadfi Booster in MenQuadfi Booster in MenQuadfi
Serogroup MenQuadfi primed (95% CI) MenACWY-TT primed (95% CI) primed + MenACWY - TT primed(95% CI)
Persistence# Booster$ Persistence# Booster$ Persistence# Booster$
N = 42 N = 40 N = 49 N = 44 N = 91 N = 84
D30- 3Y D30 - 3Y Post- D30 - 3Y Post-
Post- Post- Post- primary Post- primaryprimary primary primary dose primary dosedose dose dose dose(D0 - (D0 -(D0 - Pre- Pre-
Pre- booster boosterbooster dose) dose)dose)
Endpoint by MenQuadfi Booster in MenQuadfi Booster in MenQuadfi Booster in MenQuadfi
Serogroup MenQuadfi primed (95% CI) MenACWY-TT primed (95% CI) primed + MenACWY - TT primed(95% CI)
A% ≥ 1:8 97.6 66.7 100 89.8 83.7 100 93.4 75.8 100(Seroprotecti(87.4; (50.5; (91.2; (77.8; (70.3; (92.0; (86.2; (65.7; (95.7;on)99.9) 80.4) 100) 96.6) 92.7) 100) 97.5) 84.2) 100)% - - 100 - - 95.5 - - 97.6
Seroresponse(91.2; (84.5; (91.7;100) 99.4) 99.7)hSBA GMT 83.3 11.9 763 49.6 14.7 659 63.0 13.3 706(63.9; (8.11; (521; (32.1; (10.7; (427; (48.3; (10.5; (531; 940)109) 17.4) 1 117) 76.7) 20.2) 1 017) 82.2) 17.0)
C% ≥ 1:8 100 100 100 87.8 57.1 100 93.4 76.9 100(Seroprotecti(91.6; (91.6; (91.2; (75.2; (42.2; (92.0; (86.2; (66.9; (95.7;on)100) 100) 100) 95.4) 71.2) 100) 97.5) 85.1) 100)% - - 95.0 - - 100 - - 97.6
Seroresponse(83.1; (92.0; (91.7;99.4) 100) 99.7)hSBA GMT 594 103 5 894 29.4 11.6 1 592 118 31.8 2 969(445; (71.7; (4 325; (20.1; (7.28; (1 165; (79.3; (21.9; (2 293;793) 149) 8 031) 43.1) 18.3) 2 174) 175) 46.1) 3 844)
W% ≥ 1:8 100 97.6 97.5 95.9 83.7 100 97.8 90.1 98.8(Seroprotecti(91.6; (87.4; (86.8; (86.0; (70.3; (92.0; (92.3; (82.1; (93.5;on)100) 99.9) 99.9) 99.5) 92.7) 100) 99.7) 95.4) 100)% - - 97.5 - - 100 - - 98.8
Seroresponse(86.8; (92.0; (93.5;99.9) 100) 100)hSBA GMT 71.8 50.0 2 656 40.1 21.2 3 444 52.5 31.5 3 043(53.3; (35.9; (1 601; (30.6; (14.6; (2 387; (42.7; (24.2; (2 248;96.7) 69.5) 4 406) 52.6) 30.9) 4 970) 64.5) 41.0) 4 120)
Endpoint by MenQuadfi Booster in MenQuadfi Booster in MenQuadfi Booster in MenQuadfi
Serogroup MenQuadfi primed (95% CI) MenACWY-TT primed (95% CI) primed + MenACWY - TT primed(95% CI)
Y% ≥ 1:8 100 97.6 100 100 89.8 100 100 93.4 100(Seroprotecti(91.6; (87.4; (91.2; (92.7; (77.8; (92.0; (96.0; (86.2; (95.7;on)100) 99.9) 100) 100) 96.6) 100) 100) 97.5) 100)% - - 100 - - 100 - - 100
Seroresponse(91.2; (92.0; (95.7;100) 100) 100)hSBA GMT 105 32.5 2 013 75.8 18.2 2 806 88.1 23.8 2 396(73.9; (24.8; (1 451; (54.2; (13.8; (2 066; (69.3; (19.4; (1 919;149) 42.7) 2 792) 106) 24.0) 3 813) 112) 29.1) 2 991)
* Clinical trial identifier MET54 - NCT03205358. The trial 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-primarydose = 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 baselinewith 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 andsafety of a booster dose of MenQuadfi in children 6 through 7 years of age who had previously received aprimary dose of MenQuadfi 5 years earlier as part of study MET51 when they were 12 through 23 monthsof 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.
Table 12: 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 beforein study MET51* - (study MEQ00073**)
MenQuadfi Booster in MenQuadfi primed (95% CI)
Persistence# Booster$
Endpoint by D30 - Post-primary dose 5Y Post-primary dose N = 88
Serogroup N = 208 (D0 - Pre-booster dose)
N = 208
A
MenQuadfi Booster in MenQuadfi primed (95% CI)
Persistence# Booster$
Endpoint by D30 - Post-primary dose 5Y Post-primary dose N = 88
Serogroup N = 208 (D0 - Pre-booster dose)
N = 208% ≥ 1:890.4 (85.5; 94.0) 76.0 (69.6; 81.6) 98.9 (93.8; 100)(Seroprotection)% Seroresponse - - 93.2 (85.7; 97.5)hSBA GMT 28.9 (24.5; 34.0) 14.5 (12.0; 17.5) 1 143 (820; 1 594)
C% ≥ 1:899.5 (97.4; 100) 85.1 (79.5; 89.6) 97.7 (92.0; 99.7)(Seroprotection)% Seroresponse - - 97.7 (92.0; 99.7)hSBA GMT 1 315 (1 002; 1 724) 37.6 (29.8; 47.4) 8 933 (6 252; 12 764)
W% ≥ 1:883.7 (77.9; 88.4) 84.6 (79.0; 89.2) 100 (95.9; 100)(Seroprotection)% Seroresponse - - 98.9 (93.8; 100)hSBA GMT 25.7 (21.3; 31.0) 30.7 (24.9; 37.9) 8 656 (6 393; 11 721)
Y% ≥ 1:892.3 (87.8; 95.5) 68.8 (62.0; 75.0) 100 (95.9; 100)(Seroprotection)% Seroresponse - - 98.9 (93.8; 100)hSBA GMT 41.6 (35.0; 49.6) 12.7 (10.5; 15.4) 3 727 (2 908; 4 776)
*Clinical trial identifier MET51 - NCT02955797. The trial 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 atbaseline with a ≥ 4-fold increase at post-vaccination.
95% CI of the single proportion calculated from the exact binomial method.
Response in participants according to MenC vaccination status before priming with MenQuadfi in
MET51
The antibody responses against serogroup C following administration of a booster dose of MenQuadfiwere 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 through26 years of age
MET59 (NCT04084769) evaluated the antibody persistence of a primary dose, immunogenicity andsafety of a booster dose of MenQuadfi in adolescents and adults 13 through 26 years of age who hadreceived a single dose of MenQuadfi in study MET50 or MET43 or MenACWY-CRM in study MET50or outside of clinical trials 3-6 years prior. The antibody persistence prior to the MenQuadfi booster doseand the booster immune response were assessed according to the vaccine (MenQuadfi or MenACWY-
CRM) participants had received 3-6 years previously (see Table 13).
For all serogroups, 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.
Table 13: 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 MenQuadfi Booster in MenQuadfi MenQuadfi Booster in MenACWY-
Serogroup primed (95% CI) CRM primed (95% CI)
Persistence^ Booster$ Persistence^ Booster$
D30 - 3-6Y D06 - D30 - D30 3-6Y D06- D30 -
Post- Post- Post- Post- Post- Post- Post- Post-primary primary booste booster primary primary booster boosterdose dose r dose dose dose dose dose dose(D0 - (D0 -
Pre- Pre-
N = 376 booster N = 46 N = 174 N = booster N = 45 N =dose) 132-133 dose) 176
N = N = 140379-380
A% ≥ 1:8 94.7 72.8 91.3 99.4 81.2 71.4 95.6 99.4(Seroprotection) (91.9; (68.0; (79.2; (96.8; (73.5; (63.2; (84.9; (96.9;96.7) 77.2) 97.6) 100) 87.5) 78.7) 99.5) 100)% Seroresponse 82.6 94.8 77.8 93.2
- - (68.6; (90.4; - - (62.9; (88.4;92.2) 97.6) 88.8) 96.4)hSBA GMT 45.2 12.5 289 502 32.8 11.6 161 399(39.9; (11.1; (133; (388; (25.0; (9.41; (93.0; (318;51.1) 14.1) 625) 649) 43.1) 14.3) 280) 502)
C% ≥ 1:8 98.1 86.3 100 100 74.2 49.3 97.8 100(Seroprotection) (96.2; (82.4; (92.3; (97.9; (65.9; (40.7; (88.2; (97.9;99.2) 89.6) 100) 100) 81.5) 57.9) 99.9) 100)
Endpoint by MenQuadfi Booster in MenQuadfi MenQuadfi Booster in MenACWY-
Serogroup primed (95% CI) CRM primed (95% CI)
Persistence^ Booster$ Persistence^ Booster$
D30 - 3-6Y D06 - D30 - D30 3-6Y D06- D30 -
Post- Post- Post- Post- Post- Post- Post- Post-primary primary booste booster primary primary booster boosterdose dose r dose dose dose dose dose dose(D0 - (D0 -
Pre- Pre-
N = 376 booster N = 46 N = 174 N = booster N = 45 N =dose) 132-133 dose) 176
N = N = 140379-380
A% Seroresponse 89.1 97.1 93.3 98.9
- - (76.4; (93.4; - - (81.7; (96.0;96.4) 99.1) 98.6) 99.9)hSBA GMT 417 37.5 3 799 3 708 49.7 11.0 919 2 533(348; (31.6; (2 504; (3 146; (32.4; (8.09; (500; (2 076;500) 44.5) 5 763) 4 369) 76.4) 14.9) 1 690) 3 091)
W% ≥ 1:8 100 88.9 100 100 93.2 76.4 100 100(Seroprotection) (99.0; (85.3; (92.3; (97.9; (87.5; (68.5; (92.1; (97.9;100) 91.9) 100) 100) 96.9) 83.2) 100) 100)% Seroresponse 97.8 97.7 88.9 98.9
- - (88.5; (94.2; - - (75.9; (96.0;99.9) 99.4) 96.3) 99.9)hSBA GMT 82.7 28.8 1 928 2 290 45.1 14.9 708 2 574(73.6; (25.1; (1 187; (1 934; (34.3; (11.9; (463; (2 178;92.9) 33.0) 3 131) 2 711) 59.4) 18.6) 1 082) 3 041)
Y% ≥ 1:8 97.9 81.8 97.8 100 88.7 52.1 100 100(Seroprotection) (95.9; (77.5; (88.5; (97.9; (82.1; (43.5; (92.1; (97.9;99.1) 85.5) 99.9) 100) 93.5) 60.7) 100) 100)
Endpoint by MenQuadfi Booster in MenQuadfi MenQuadfi Booster in MenACWY-
Serogroup primed (95% CI) CRM primed (95% CI)
Persistence^ Booster$ Persistence^ Booster$
D30 - 3-6Y D06 - D30 - D30 3-6Y D06- D30 -
Post- Post- Post- Post- Post- Post- Post- Post-primary primary booste booster primary primary booster boosterdose dose r dose dose dose dose dose dose(D0 - (D0 -
Pre- Pre-
N = 376 booster N = 46 N = 174 N = booster N = 45 N =dose) 132-133 dose) 176
N = N = 140379-380
A% Seroresponse 95.7 98.9 91.1 100
- - (85.2; (95.9; - - (78.8; (97.9;99.5) 99.9) 97.5) 100)hSBA GMT 91.0 21.8 1 658 2 308 36.1 8.49 800 3 036(78.6; (18.8; (973; (1 925; (27.2; (6.50; (467; (2 547;105) 25.1) 2 826) 2 767) 47.8) 11.1) 1 371) 3 620)
*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 ofparticipants 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 baselinewith 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, andsafety 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 wereassessed according to the vaccine (MenQuadfi or MenACWY-PS) adults had received 3 years previouslyin MET49 (Table 14).
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 forthese serogroups) and were comparable for serogroup A.
Table 14: 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 instudy MET49* - (study MEQ00066#)
Endpoint by MenQuadfi Booster in MenQuadfi MenQuadfi Booster in MenACWY-PS
Serogroup primed (95% CI) primed (95% CI)
Persistence^ Booster$ Persistence^ Booster$
D30 - 3Y Post- D06 - D30 - D30 3Y D06 - D30 -
Post- primary Post- Post- Post- Post- Post- Post-primary dose booste booster primary primary booster boosterdose (D0 - r dose dose dose dose dose dose
Pre- (D0 -
N = 58 N = N = 62 N = 130booster Pre-
N = 214 dose) boosterdose)
N = 169
N = 214
N = 169
A% ≥ 1:8 89.6 65.0 91.4 93.8 85.7 65.7 72.6 87.7(Seroprotection) (84.7; (58.2; (81.0; (88.5; (79.5; (58.0; (59.8; (80.8;93.4) 71.3) 97.1) 97.1) 90.6) 72.8) 83.1) 92.8)% Seroresponse 36.2 79.3 8.1 (2.7; 60.8
- - (24.0; (71.8; - - 17.8) (51.8;49.9) 85.6) 69.2)hSBA GMT 48.9 12.2 43.7 162 37.7 11.6 13.1 56.6(39.0; (10.2; (26.5; (121; (29.3; (9.53; (9.60; (41.5;61.5) 14.6) 71.9) 216) 48.7) 14.1) 17.8) 77.2)
C% ≥ 1:8 88.2 73.4 98.3 99.3 71.4 47.9 51.6 85.3(Seroprotection) (83.1; (66.9; (90.8; (96.2; (64.0; (40.2; (38.6; (78.0;92.2) 79.2) 100) 100) 78.1) 55.7) 64.5) 90.9)% Seroresponse - - 77.6 93.1 - - 8.1 (2.7; 55.0(64.7; (87.7; (46.0;
Endpoint by MenQuadfi Booster in MenQuadfi MenQuadfi Booster in MenACWY-PS
Serogroup primed (95% CI) primed (95% CI)
Persistence^ Booster$ Persistence^ Booster$
D30 - 3Y Post- D06 - D30 - D30 3Y D06 - D30 -
Post- primary Post- Post- Post- Post- Post- Post-primary dose booste booster primary primary booster boosterdose (D0 - r dose dose dose dose dose dose
Pre- (D0 -
N = 58 N = N = 62 N = 130booster Pre-
N = 214 dose) boosterdose)
N = 169
N = 214
N = 16987.5) 96.6) 17.8) 63.8)hSBA GMT 84.8 17.7 206 638 26.7 8.47 11.1 56.0(64.0; (14.3; (126; (496; (19.8; (6.76; (7.17; (39.7;112) 21.9) 339) 820) 36.0) 10.6) 17.1) 78.9)
W% ≥ 1:8 78.8 66.8 89.7 98.6 60.1 39.6 46.8 80.8(Seroprotection) (72.6; (60.1; (78.8; (95.1; (52.3; (32.2; (34.0; (72.9;84.1) 73.1) 96.1) 99.8) 67.6) 47.4) 59.9) 87.2)% Seroresponse 70.7 90.3 - 6.5 (1.8; 49.2
- - (57.3; (84.3; - 15.7) (40.4;81.9) 94.6) 58.1)hSBA GMT 28.0 14.2 118 419 14.7 6.54 9.89 31.0(22.2; (11.6; (64.0; (317; (11.0; (5.28; (6.45; (22.6;35.3) 17.4) 216) 553) 19.8) 8.11) 15.2) 42.6)
Y% ≥ 1:8 92.5 68.2 94.8 100 65.5 40.8 45.2 81.5(Seroprotection) (88.0; (61.5; (85.6; (97.5; (57.8; (33.3; (32.5; (73.8;95.6) 74.4) 98.9) 100) 72.6) 48.6) 58.3) 87.8)% Seroresponse 72.4 92.4 - - 8.1 (2.7; 49.2
- - (59.1; (86.8; 17.8) (40.4;83.3) 96.2) 58.1)hSBA GMT 65.3 15.3 151 566 19.6 7.49 11.1 40.5(51.8; (12.3; (83.4; (433; (14.4; (5.72; (6.31; (29.0;82.2) 19.1) 274) 740 26.7) 9.82) 19.4) 56.4)
* Clinical trial identifier: NCT02842866# Clinical trial identifier: NCT04142242^N calculated using full analysis set for persistence (FASP) with valid serology results; Post primarydose = 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 atbaseline with a ≥ 4-fold increase at post-vaccination.
95% CI of the single proportion calculated using the exact binomial method.
5-year persistence
A subset of adults (N = 52) who were assessed for antibody persistence at 3 years and did not receive thebooster dose were re-assessed for antibody persistence at 5 years at which time they received a boosterdose of MenQuadfi. In MenQuadfi-primed participants, hSBA GMTs for serogroups C, W and Y 5Ypost-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, and95.0% for serogroup W in participants primed with MenQuadfi and 87.5%, 62.5%, 87.5% and 68.8% forserogroups A, C, W and Y, respectively, for those participants primed with MenACWY-PS. Additionally,hSBA GMTs were higher and seroresponse rates were higher or trended higher for all serogroups inindividuals primed with MenQuadfi compared to those primed with MenACWY-PS.
6-7 year persistence
Antibody persistence 6-7 years after primary vaccination of adults in study MET44 with either
MenQuadfi or MenACWY-PS has been evaluated (Table 15).
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 15: 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 D30 - Post- 6-7Y Post-primary D30 - Post- 6-7Y Post-primary
Serogroup primary dose$ dose# primary dose$ dose#
N = 59 N = 59 N = 26 N = 26
A% ≥ 1:8 91.4 (81.0; 97.1) 55.9 (42.4; 68.8) 76.9 (56.4; 91.0) 50.0 (29.9; 70.1)(Seroprotection)
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 74.1 (61.0; 84.7) 59.3 (45.7; 71.9) 76.9 (56.4; 91.0) 42.3 (23.4; 63.1)(Seroprotection)
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 75.9 (62.8; 86.1) 66.1 (52.6; 77.9) 73.1 (52.2; 88.4) 38.5 (20.2; 59.4)(Seroprotection)
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 81.0 (68.6; 90.1) 59.3 (45.7; 71.9) 73.1 (52.2; 88.4) 46.2 (26.6; 66.6)(Seroprotection)
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 participants in full analysis set for persistence (FASP) with valid serology results.
$ Post primary dose = D30 of MET44# 6-7Y Post-primary dose = D0 of MEQ0006695% 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 MenACWYvaccines
MET56 (NCT02752906) compared the immunogenicity of a booster dose of MenQuadfi with a boosterdose of MenACWY-DT in participants at least 15 years of age. These participants were primed with aquadrivalent 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 16: Comparison of bactericidal antibody responses to MenQuadfi and MenACWY-DT30 days after booster vaccination in participants at least 15 years of age primed with MenACWY-
CRM or MenACWY-DT 4 to 10 years earlier (study MET56*)
Endpoint by Serogroup MenQuadfi MenACWY-DT (95% CI)(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)
Endpoint by Serogroup MenQuadfi MenACWY-DT (95% CI)(95% CI)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 participants 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.
Immunogenicity following two doses of MenQuadfi at 3 and 12-13 months of age in infants receiving
Bexsero vaccine during the first year of life
MET52 (NCT03632720) evaluated the immunogenicity of MenQuadfi in infants vaccinated with Bexseroat 2 and 4 months of age and MenQuadfi at 3 months, with a booster dose of MenQuadfi given at 12-13 months of age with and without Bexsero (N=347). The percentages of participants who achievedseroprotection (hSBA titres ≥1:8) 30 days following administration of MenQuadfi booster dose alone orco-administered with Bexsero at 12-13 months were 99.4% -100% for all four serogroups; immuneresponses to Bexsero were not evaluated. Of note, 59.1% of evaluated participants had hSBA titres > 1:8against serogroup A, 25.9% against serogroup C, 22.2% against serogroup Y, and 8.3% against serogroup
W before first MenQuadfi administration at 3 months of age. It remains unclear whether this was due tocross reactivity of Bexsero vaccination at 2 months of age or external influence as no samples were takento establish baseline levels before the first vaccination with Bexsero.
Preterm infants
Immune responses elicited by MenQuadfi given as three primary doses at 2, 4, and 6 months of agefollowed by a booster dose in the second year of life in infants with a history of preterm birth (31 to<37 weeks gestational age) (N=61-71) were compared to infants who were born full term in study
MET42 (Table 17).
Table 17: Seroprotection rates (hSBA titre ≥1:8) in infants with a history of preterm vs full termbirth (study MET42)
Preterm (GA 31 to <37 weeks) Full term (GA ≥37 weeks)
Serogroup Study timepoint Group 1a* Group 1b** Group 1a* Group 1b**(N=45) (N=26) (N=602) (N=269)
D30 after primary 65.7 (47.8; 85.7 (63.7; 78.1 (74.3; 76.3series 80.9) 97.0) 81.6) (70.3;81.5)
D0 before booster 57.1 (41.0; 62.5 (40.6; 59.1 (55.0; 55.6 (49.3;
Adose 72.3) 81.2) 63.2) 61.7)
D30 after booster 88.9 (73.9; 84.2 (60.4; 87.6 (84.7; 93.2 (89.4;dose 96.9) 96.6) 90.1) 95.9)
D30 after primary 99.0 (97.7; 98.7 (96.3;100 (90.5; 100) 100 (84.6; 100)series 99.7) 99.7)
D0 before booster 91.1 (78.8; 73.1 (52.2; 93.1 (90.7; 84.7 (79.8;
Cdose 97.5) 88.4) 95.0) 88.8)
D30 after booster 99.4 (98.3; 99.3 (97.4;100 (91.0; 100) 100 (80.5; 100)dose 99.8) 99.9)
D30 after primary 91.7 (73.0; 98.7 (97.3; 98.4 (95.9;100 (91.0; 100)series 99.0) 99.5) 99.6)
D0 before booster 97.8 (88.2; 88.5 (69.8; 97.2 (95.5; 95.9 (92.8;
Wdose 99.9) 97.6) 98.3) 97.9)
D30 after booster 99.3 (98.3;100 (90.5; 100) 100 (81.5; 100) 100 (98.6; 100)dose 99.8)
D30 after primary 95.2 (76.2; 98.5 (97.0; 98.7 (96.4;100 (91.0; 100)series 99.9) 99.3) 99.7)
D0 before booster 97.6 (87.4; 92.3 (74.9; 96.8 (95.0; 95.9 (92.8;
Ydose 99.9) 99.1) 98.1) 97.9)
D30 after booster 99.0 (97.9; 99.3 (97.4;100 (91.0; 100) 100 (81.5; 100)dose 99.6) 99.9)
* Group 1a: MenQuadfi and routine vaccines at 2,4,6, and 12-15 months of age.
** Group 1b: MenQuadfi at 2,4,6, and 15-18 months and routine vaccines at 2,4,6, 12-15 months of age,and 15-18 months of age.
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 reproductivetoxicity study in female rabbits.
The administration of MenQuadfi to female rabbits at a full human dose showed no effects on matingperformance, female fertility, no teratogenic potential, and no effect on pre- or post-natal development.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium chloride
Sodium acetate (E 262)
Water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinalproducts.
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. Atthe end of this period, MenQuadfi should be used or discarded. These data are intended to guidehealthcare 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
The vaccine should be inspected visually for any particulate matter and/or variation of physical aspect (ordiscolouration) prior to administration. In the event of either being observed, discard the vaccine.
PreparationPack 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 fromthe 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 needlesSpecific instructions for luer-lok syringe
To attach the needle to the syringe, gently twist the needle clockwise into the syringe until slightresistance is felt. Before injection, remove the vial flip off seal and withdraw 0.5 mL of solution from thevial, ensuring no air bubbles are present. A new needle should be used to administer the vaccine.
DisposalAny unused medicinal product or waste material should be disposed of in accordance with localrequirements.
10. DATE OF REVISION OF THE TEXT
Detailed information on this medicinal product is available on the website of the European Medicines
Agency https://www.ema.europa.eu.
Compensation lists for MENQUADFI Sanofi
E2 - Sublist E - section E2 with 100% discount from the reference price
- Price
- 334.73 RON
- Copayment
- 334.73 RON
- Patient
- 0.00 RON