Immunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine When Co-administered With Routine Pediatric Vaccines in Healthy Infants and Toddlers in Europe

Study Overview
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Brief Summary
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Primary objective is to demonstrate the non-inferiority of the antibody response against meningococcal serogroups A, C, Y, and W following the administration of a 3-dose series of MenACYW conjugate vaccine compared to a 3-dose series of a licensed meningococcal vaccine when each vaccine is given concomitantly with routine pediatric vaccines (10-valent pneumococcal vaccine and diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b [DTaP-IPV-HB-Hib vaccine]) to infants and toddlers 6 weeks to 18 months old Secondary objectives are: To demonstrate the non-inferiority of the antibody (Ab) response against meningococcal serogroups A, C, Y, and W following the administration of 2 doses in infancy of MenACYW conjugate vaccine compared to 2 doses of a licensed meningococcal vaccine when each vaccine is given concomitantly with routine pediatric vaccines (10-valent pneumococcal vaccine and DTaP-IPV-HB-Hib vaccine) to infants and toddlers 6 weeks to 18 months old. To describe the Ab responses against meningococcal groups A, C, Y, and W and the antigens of the routine pediatric vaccines administered in the study.

Official Title
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Immunogenicity and Safety Study of an Investigational Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers in Europe

Conditions
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Meningococcal Infections

Intervention / Treatment
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* Biological: MenACYW conjugate vaccine
* Biological: Meningococcal group A, C, W-135, and Y conjugate vaccine
* Biological: DTaP-IPV-HB-Hib vaccine
* Biological: Pneumococcal vaccine (13-valent)
* Biological: Pneumococcal vaccine (10-valent)
* Biological: MMR vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 42 to ≤ 89 days on the day of the first study visit Healthy infants as determined by medical history, physical examination and judgment of the Investigator Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative Subject and parent/legally acceptable representative are able to attend all scheduled visits and to comply with all study procedures Covered by health insurance according to local regulations Exclusion Criteria: articipation at the time of study enrollment (or in the 4 weeks preceding the first study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure Receipt of any vaccine in the 4 weeks preceding the first study vaccination or planned receipt of any vaccine in the 4 weeks before and/or following any study vaccination except for influenza vaccination and rotavirus vaccination, which may be received at a gap of at least 2 weeks before or 2 weeks after any study vaccines. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines. This exclusion criterion does not apply to subjects in Finland, Sweden or Poland who plan to receive the licensed rotavirus vaccine concomitantly with study vaccines at study vaccination visits V1 and V2. Receipt or planned to receipt during the study period vaccination against meningococcal disease with either the study vaccine or another vaccine (i.e., mono- or polyvalent, polysaccharide, or conjugate meningococcal vaccine containing serogroups A, C, Y, or W; or meningococcal B serogroup-containing vaccine) Previous vaccination against diphtheria, tetanus, pertussis, Haemophilus influenzae type B (Hib), poliovirus, Streptococcus pneumoniae, measles, mumps, or rubella. Previous vaccination against hepatitis B when administered to risk groups, as per local recommendation. Receipt of immune globulins, blood or blood-derived products since birth Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks) since birth Family history of congenital or hereditary immunodeficiency, unless the immune competence of the potential vaccine recipient is demonstrated Individuals with blood dyscrasias, leukemia, lymphoma of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems Individuals with active tuberculosis History of Neisseria meningitidis infection, confirmed either clinically, serologically, or microbiologically History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, measles, mumps, rubella, and of Haemophilus influenzae type b, and / or Streptococcus pneumoniae infection or disease At high risk for meningococcal infection during the study (specifically, but not limited to, subjects with persistent complement deficiency, with anatomic or functional asplenia, or subjects traveling to countries with high endemic or epidemic disease) Individuals with underlying conditions predisposing them to invasive pneumococcal disease (specifically, but not limited to, subjects with sickle cell disease or human immunodeficiency virus [HIV] infection) History of any neurologic disorders, including seizures and progressive neurologic disorders History of Guillain-Barré syndrome Known systemic hypersensitivity to any of the vaccine components, or history of a severe allergic reaction (e.g., anaphylaxis) to the vaccine(s) used in the study or to a vaccine containing any of the same substances including neomycin, streptomycin, polymyxin B, glutaraldehyde, formaldehyde, and gelatin Verbal report of thrombocytopenia, contraindicating intramuscular vaccination in the investigator's opinion Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination in the investigator's opinion Chronic illness (including, but not limited to, cardiac disorders, congenital heart disease, chronic lung disease, renal disorders, auto-immune disorders, diabetes, psychomotor diseases, and known congenital or genetic diseases) that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion Any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives, including planning to leave the area of the study site before the end of the study Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C). A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided. Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study Infants born preterm (by less than 37 weeks of gestation) requiring specific immunization schedule for routine childhood vaccines and/or specific care at the time of vaccination, as per national recommendations

Ages Eligible for Study
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Minimum Age: 42 Days
Maximum Age: 89 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>MenACYW conjugate vaccine, 3 doses, co-administered with routine vaccines (10-valent pneumococcal vaccine, DTaP-IPV-HB-Hib vaccine, and measles, mumps, and rubella [MMR] vaccine) at 2, 4 and 12 to 18 months of age | Biological: MenACYW conjugate vaccine<br>* Meningococcal polysaccharide (serogroups A,C,Y and W) tetanus toxoid conjugate vaccine, 0.5 mL, intramuscular<br>* Other names: MenQuadfi®;Biological: DTaP-IPV-HB-Hib vaccine<br>* Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b vaccine<br>* Other names: Hexyon®/Hexacima®;Biological: Pneumococcal vaccine (10-valent)<br>* Pneumococcal polysaccharide conjugate vaccine (10-valent, adsorbed)<br>* Other names: Synflorix®;Biological: MMR vaccine<br>* Measles, mumps, and rubella vaccine<br>* Other names: M-M-RVAXPRO®;|
| Active Comparator: Group 2<br>Licensed meningococcal vaccine (Nimenrix®), 3 doses, co-administered with routine vaccines (10-valent pneumococcal vaccine, DTaP-IPV- HB-Hib vaccine, and MMR vaccine) at 2, 4 and 12 to 18 months of age | Biological: Meningococcal group A, C, W-135, and Y conjugate vaccine<br>* Meningococcal group A, C, W-135, and Y conjugate vaccine, 0.5 mL, intramuscular<br>* Other names: Nimenrix®;Biological: DTaP-IPV-HB-Hib vaccine<br>* Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b vaccine<br>* Other names: Hexyon®/Hexacima®;Biological: Pneumococcal vaccine (10-valent)<br>* Pneumococcal polysaccharide conjugate vaccine (10-valent, adsorbed)<br>* Other names: Synflorix®;Biological: MMR vaccine<br>* Measles, mumps, and rubella vaccine<br>* Other names: M-M-RVAXPRO®;|
| Experimental: Group 3<br>MenACYW conjugate vaccine, 3 doses, co-administered with routine vaccines (13-valent pneumococcal vaccine, DTaP-IPV-HB-Hib vaccine, and MMR vaccine) at 2, 4 and 12 to 18 months of age | Biological: MenACYW conjugate vaccine<br>* Meningococcal polysaccharide (serogroups A,C,Y and W) tetanus toxoid conjugate vaccine, 0.5 mL, intramuscular<br>* Other names: MenQuadfi®;Biological: DTaP-IPV-HB-Hib vaccine<br>* Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b vaccine<br>* Other names: Hexyon®/Hexacima®;Biological: Pneumococcal vaccine (13-valent)<br>* Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)<br>* Other names: Prevenar 13®;Biological: MMR vaccine<br>* Measles, mumps, and rubella vaccine<br>* Other names: M-M-RVAXPRO®;|
| Experimental: Group 4<br>MenACYW conjugate vaccine, 4 doses, co-administered with routine vaccines (13-valent pneumococcal vaccine, DTaP-IPV-HB-Hib vaccine, and MMR vaccine) at 2, 4, and 12 to 18 months of age and administered alone at 6 months of age | Biological: MenACYW conjugate vaccine<br>* Meningococcal polysaccharide (serogroups A,C,Y and W) tetanus toxoid conjugate vaccine, 0.5 mL, intramuscular<br>* Other names: MenQuadfi®;Biological: DTaP-IPV-HB-Hib vaccine<br>* Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b vaccine<br>* Other names: Hexyon®/Hexacima®;Biological: Pneumococcal vaccine (13-valent)<br>* Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)<br>* Other names: Prevenar 13®;Biological: MMR vaccine<br>* Measles, mumps, and rubella vaccine<br>* Other names: M-M-RVAXPRO®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody titers against meningococcal serogroups A, C, Y, and W (groups 1 and 2) | Antibody titers will be measured by the serum bactericidal assay using human complement (hSBA) and expressed as geometric mean titers (GMTs) | 30 days after dose 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody titers ≥ 1:8 against meningococcal serogroups A, C, Y, and W (groups 1 and 2) | Percentage of participants achieving antibody titers ≥ predefined threshold of 1:8, measured by hSBA | D0, 30 days after Dose 2 and before and 30 days after the booster dose | 
| Antibody titers above pre-defined thresholds for meningococcal serogroups A, C, Y, and W (all groups) | Percentage of participants achieving antibody titers ≥ predefined thresholds, measured by hSBA | D0, 30 days after Dose 2 and before and 30 days after booster Dose 3 for groups 1, 2, 3. D0, 30 days after Dose 3 and before and 30 days after booster Dose 4 for group 4 | 
| Antibody titers against meningococcal serogroups A, C, Y, and W (all groups) | Antibody titers will be measured by hSBA and expressed as GMTs | D0, 30 days after Dose 2 and before and 30 days after booster Dose 3 for groups 1, 2, 3. D0, 30 days after Dose 3 and before and 30 days after booster Dose 4 for group 4 | 
| Antibody concentrations against pre-defined thresholds for antigens of DTaP-IPV-HB-Hib vaccine (all groups) | Percentage of participants with antibody concentrations ≥ established seroprotection cut-off levels for diphtheria, tetanus, polio, hepatitis B and Hib, and seroresponse rate for anti-pertussis antibodies | 30 days after dose 2, 30 days after booster dose 3 (group 3), or 30 days after booster dose 4 (group 4) | 
| Antibody concentrations/titers against antigens of DTaP-IPV- HB-Hib vaccine (all groups) | Antibody concentrations/titers will be measured by standard assays for the antigens contained in the vaccine and expressed as geometric mean concentrations/titers (GMCs/GMTs) | 30 days after dose 2, 30 days after booster dose 3 (group 3), or 30 days after booster dose 4 (group 4) | 
| Antibody concentrations above pre-defined thresholds for antigens of 10-valent pneumococcal vaccine (groups 1 and 2) | Percentage of participants with antibody concentrations ≥ established seroprotection cut-off levels for antigens in the pneumococcal vaccine | 30 days after dose 2 and 30 days after booster dose | 
| Antibody concentrations against antigens of 10-valent pneumococcal vaccine (groups 1 and 2) | Antibody concentrations will be measured by standard assays for the antigens contained in the vaccine and expressed as geometric mean concentrations (GMCs) | 30 days after dose 2 and 30 days after booster dose | 
| Antibody concentrations above pre-defined thresholds for antigens of 13-valent pneumococcal vaccine (group 3 and 4) | Percentage of participants with antibody concentrations ≥ established seroprotection cut-off levels for antigens in the pneumococcal vaccine | 30 days after dose 2 and 30 days after booster dose 3 (group 3) or 30 days after booster dose 4 (group 4) | 
| Antibody concentrations against antigens of 13-valent pneumococcal vaccine (group 3 and 4) | Antibody concentrations will be measured by standard assays for the antigens contained in the vaccine and expressed as geometric mean concentrations (GMCs) | 30 days after dose 2 and 30 days after booster dose 3 (group 3) or 30 days after booster dose 4 (group 4) | 
| Antibody concentrations above pre-defined thresholds for antigens of MMR vaccine (all groups) | Percentage of participants with antibody concentrations ≥ established seroprotection cut-off levels for antigens in MMR vaccine | 30 days after the booster dose | 
| Antibody concentrations against antigens of MMR vaccine (all groups) | Antibody concentrations will be measured by standard assays for the antigens contained in the vaccine | 30 days after the booster dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meningococcal meningitis, MenACYW conjugate vaccine, Quadrivalent meningococcal vaccine