Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers in the US

Study Overview
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Brief Summary
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The purpose of this study is to compare the immunogenicity and describe the safety of MenACYW conjugate vaccine and MENVEO® when both are administered concomitantly with routine pediatric vaccines to healthy infants and toddlers in the US.

Detailed Description
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The duration of each subject's participation in the trial will be approximately 16 to 19 months (Subgroup 1a) and 19 to 22 months (Subgroup 1b and Group 2), which includes a safety follow up contact at 6 months after the last vaccinations.

Official Title
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A Phase III, Partially Modified Double-blind, Randomized, Parallel-group, Active-controlled, Multi-center Study to Compare the Immunogenicity and Describe the Safety of MenACYW Conjugate Vaccine and MENVEO® When Administered Concomitantly With Routine Pediatric Vaccines to Healthy Infants and Toddlers in the United States

Conditions
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Healthy Volunteers (Meningococcal Infection)

Intervention / Treatment
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* Biological: MenACYW conjugate vaccine
* Biological: MenACYW-135 conjugate vaccine
* Biological: DTaP-IPV//Hib vaccine
* Biological: Pneumococcal 13-valent conjugate vaccine
* Biological: Pentavalent rotavirus vaccine
* Biological: Hepatitis B vaccine
* Biological: Measles, mumps, rubella (MMR) vaccine
* Biological: Varicella vaccine
* Biological: Hepatitis A 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 guardian, and an independent witness, if required by local regulations Participant and parent/guardian are able to attend all scheduled visits and to comply with all trial procedures. Infants who received the first dose of hepatitis B vaccine at least 28 days before the first study visit Exclusion Criteria: Participation at the time of study enrollment or in the 4 weeks preceding the first trial vaccination or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure Receipt of any vaccine in the 4 weeks preceding the first trial vaccination or planned receipt of any vaccine in the 4 weeks before and/or following any trial vaccination except for influenza vaccination, which may be received at a gap of at least 2 weeks before or 2 weeks after any study vaccination. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines Previous vaccination against meningococcal disease with either the trial vaccine or another vaccine (i.e., mono- or polyvalent, PS, or conjugate meningococcal vaccine containing serogroups A, C, Y, or W; or meningococcal B serogroup-containing vaccine). Previous vaccination against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis A, measles, mumps, rubella, varicella; and of Haemophilus influenzae type b, Streptococcus pneumoniae, and /or rotavirus infection or disease Receipt of more than 1 previous dose of hepatitis B vaccine 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, until 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 any Neisseria meningitidis infection, confirmed either clinically, serologically, or microbiologically History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, hepatitis A, measles, mumps, rubella, varicella; and of Haemophilus influenzae type b, Streptococcus pneumoniae, and /or rotavirus infection or disease At high risk for meningococcal infection during the trial (specifically, but not limited to, subjects with persistent complement deficiency, with anatomic or functional asplenia, or subjects travelling to countries with high endemic or epidemic disease) History of intussusception History of any neurologic disorders, including any seizures and progressive neurologic disorders History of Guillain-Barré syndrome Known systemic hypersensitivity to any of the vaccine components or to latex, or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances, including neomycin, gelatin, and yeast 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 Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw 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 trial conduct or completion Any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided Identified as a natural or adopted child of the investigator or employee with direct involvement in the proposed study The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

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 1a<br>MenACYW conjugate vaccine and routine vaccines at 2, 4, 6, and 12 to 15 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>Biological: DTaP-IPV//Hib vaccine<br>* DTaP-IPV//Hib vaccine at 2, 4, and 6 months of age, Intramuscular<br>* Other names: Pentacel®;Biological: Pneumococcal 13-valent conjugate vaccine<br>* Pneumococcal vaccine at 2, 4, 6, and 12 months of age, Intramuscular<br>* Other names: PREVNAR 13®;Biological: Pentavalent rotavirus vaccine<br>* Rotavirus vaccine at 2, 4, and 6 months of age, oral solution<br>* Other names: RotaTeq®;Biological: Hepatitis B vaccine<br>* Hepatitis B vaccine at 2 and 6 months of age, Intramuscular<br>* Other names: ENGERIX-B®;Biological: Measles, mumps, rubella (MMR) vaccine<br>* MMR vaccine at 12 months of age, Subcutaneous<br>* Other names: M-M-R® II;Biological: Varicella vaccine<br>* Varicella vaccine at 12 months of age<br>* Other names: VARIVAX®;|
| Experimental: Group 1b<br>MenACYW conjugate vaccine at 2, 4, 6, and 15 to 18 months of age and routine vaccines at 2, 4, 6, 12 to 15 months of age, and 15 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>Biological: DTaP-IPV//Hib vaccine<br>* DTaP-IPV//Hib vaccine at 2, 4, and 6 months of age, Intramuscular<br>* Other names: Pentacel®;Biological: Pneumococcal 13-valent conjugate vaccine<br>* Pneumococcal vaccine at 2, 4, 6, and 12 months of age, Intramuscular<br>* Other names: PREVNAR 13®;Biological: Pentavalent rotavirus vaccine<br>* Rotavirus vaccine at 2, 4, and 6 months of age, oral solution<br>* Other names: RotaTeq®;Biological: Hepatitis B vaccine<br>* Hepatitis B vaccine at 2 and 6 months of age, Intramuscular<br>* Other names: ENGERIX-B®;Biological: Measles, mumps, rubella (MMR) vaccine<br>* MMR vaccine at 12 months of age, Subcutaneous<br>* Other names: M-M-R® II;Biological: Varicella vaccine<br>* Varicella vaccine at 12 months of age<br>* Other names: VARIVAX®;Biological: Hepatitis A vaccine<br>* Hepatitis A vaccine at 15 to 18 months of age<br>* Other names: HAVRIX®;|
| Active Comparator: Group 2a<br>MENVEO® at 2, 4, 6, and 12 months of age and routine vaccines at 2, 4, 6, 12, and 15 to 18 months of age | Biological: MenACYW-135 conjugate vaccine<br>* Meningococcal (Groups A, C, Y and W-135) oligosaccharide diphtheria CRM197 conjugate vaccine, 0.5 mL, intramuscular<br>* Other names: MENVEO®;Biological: DTaP-IPV//Hib vaccine<br>* DTaP-IPV//Hib vaccine at 2, 4, and 6 months of age, Intramuscular<br>* Other names: Pentacel®;Biological: Pneumococcal 13-valent conjugate vaccine<br>* Pneumococcal vaccine at 2, 4, 6, and 12 months of age, Intramuscular<br>* Other names: PREVNAR 13®;Biological: Pentavalent rotavirus vaccine<br>* Rotavirus vaccine at 2, 4, and 6 months of age, oral solution<br>* Other names: RotaTeq®;Biological: Hepatitis B vaccine<br>* Hepatitis B vaccine at 2 and 6 months of age, Intramuscular<br>* Other names: ENGERIX-B®;Biological: Measles, mumps, rubella (MMR) vaccine<br>* MMR vaccine at 12 months of age, Subcutaneous<br>* Other names: M-M-R® II;Biological: Varicella vaccine<br>* Varicella vaccine at 12 months of age<br>* Other names: VARIVAX®;|
| Active Comparator: Group 2b<br>MENVEO® at 2, 4, 6, and 12 months of age and routine vaccines at 2, 4, 6, 12, and 15 to 18 months of age | Biological: MenACYW-135 conjugate vaccine<br>* Meningococcal (Groups A, C, Y and W-135) oligosaccharide diphtheria CRM197 conjugate vaccine, 0.5 mL, intramuscular<br>* Other names: MENVEO®;Biological: DTaP-IPV//Hib vaccine<br>* DTaP-IPV//Hib vaccine at 2, 4, and 6 months of age, Intramuscular<br>* Other names: Pentacel®;Biological: Pneumococcal 13-valent conjugate vaccine<br>* Pneumococcal vaccine at 2, 4, 6, and 12 months of age, Intramuscular<br>* Other names: PREVNAR 13®;Biological: Pentavalent rotavirus vaccine<br>* Rotavirus vaccine at 2, 4, and 6 months of age, oral solution<br>* Other names: RotaTeq®;Biological: Hepatitis B vaccine<br>* Hepatitis B vaccine at 2 and 6 months of age, Intramuscular<br>* Other names: ENGERIX-B®;Biological: Measles, mumps, rubella (MMR) vaccine<br>* MMR vaccine at 12 months of age, Subcutaneous<br>* Other names: M-M-R® II;Biological: Varicella vaccine<br>* Varicella vaccine at 12 months of age<br>* Other names: VARIVAX®;Biological: Hepatitis A vaccine<br>* Hepatitis A vaccine at 15 to 18 months of age<br>* Other names: HAVRIX®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody titers above predefined thresholds against meningococcal serogroups A, C, Y, and W (Subgroup 1a and 2a) | Percentage of participants achieving a seroresponse, measured by the serum bactericidal assay using human complement (hSBA) | D0 and 30 days after the fourth meningococcal vaccination for subgroup 1a and 2a | 
| Antibody titers ≥ 1:8 against meningococcal serogroups A, C, Y, and W (group 1 and 2) | Percentage of participants achieving antibody titers ≥ predefined threshold of 1:8, measured by hSBA | 30 days after vaccination at 6 months of age for group 1 and 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IgG antibody concentrations ≥ 10 milli-international units (mIU) / mL against hepatitis B | Percentage of participants who achieving IgG antibody concentrations ≥ predefined threshold of 10 mIU/mL | 30 days after vaccination at 6 months of age for group 1 and 2 | 
| IgG antibody concentrations against hepatitis B | 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 vaccination at 6 months of age for group 1 and group 2 | 
| Antibody concentrations against polyribosyl-ribitol phosphate (PRP) | 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 vaccination at 6 months, before and 30 days after 15-months vaccination for subgroup 1b and 2b | 
| Antibody concentrations ≥ 0.15 and/or ≥ 1.0 µg/mL against PRP | Percentage of subjects achieving antibody concentrations ≥ predefined thresholds of 0.15 µg/mL and/or 1.0 µg/mL | 30 days after vaccination at 6 months of age for group 1 and group 2, before and 30 days after vaccination at 15 months of age for subgroup 1b and 2b | 
| Antibody concentrations above predefined threshold against diphteria and tetanus | % of participants with antibody concentrations ≥ established serostatus cut-off levels for diphteria and tetanus | 30 days after vaccination at 6 months for group 1 and 2, 30 days after 15-months vaccination for subgroup 1b and 2b | 
| Antibody concentrations against diphteria and tetanus | 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 vaccination at 6 months for group 1 and 2, 30 days after 15-months vaccination for subgroup 1b and 2b | 
| Antibody titers ≥ 1:8 against poliovirus types 1, 2, and 3 | Percentage of participants achieving antibody titers ≥ predefined threshold of 1:8 | 30 days after vaccination at 6 months for group 1 and group 2, 30 days after vaccination at 15 months of age for subgroup 1b and 2b | 
| Antibody titers against poliovirus types 1,2,3 | Antibody titers will be measured by standard assays for the antigens contained in the vaccine and expressed as geometric mean titers (GMTs) | 30 days after vaccination at 6 months of age for group 1 and group 2, 30 days after vaccination at 15 months of age for subgroup 1b and 2b | 
| IgA antibody concentrations with ≥ 3-fold rise over baseline for antigens of 5 serogroups of rotavirus | Percentage of participants achieving IgA antibody concentrations ≥ predefined threshold of 3-fold rise over baseline | D0 and 30 days after vaccination at 6 months of age for group 1 and 2 | 
| IgA antibody concentrations against antigens of 5 serogroups of rotavirus | Antibody concentrations will be measured by standard assays for the antigens contained in the rotavirus vaccine and expressed as geometric mean concentrations (GMCs) | D0 and 30 days after vaccination at 6 months of age for group 1 and 2 | 
| Antibody concentrations against pertussis (pertussis toxoid [PT], filamentous hemagglutinin [FHA], pertactin [PRN], fimbriae types 2 and 3 [FIM]) | Antibody concentrations will be measured by standard assays for the antigens contained in the vaccine and expressed as geometric mean concentrations (GMCs) | D0 and 30 days after vaccination at 6- months of age for group 1 and 2, before and after the 15-months vaccinations for subgroup 1b and 2b | 
| Antibody concentrations above predefined threshold against pertussis (PT, FHA, PRN, FIM) | % of participants with antibody concentrations ≥ established seroresponse rate for pertussis | before and after the vaccination at 15 months of age for subgroup 1b and 2b | 
| Antibody concentrations against antigens of 13-valent pneumococcal vaccine | 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 vaccination at 6 months for group 1 and 2, 30 days after vaccination at 12 months for subgroup 1a and 2a | 
| Antibody concentrations above predefined thresholds for antigens of MMR vaccine | % of participants with antibody concentrations ≥ established serostatus cut-off levels for antigens in MMR vaccine | 30 days after the 12-month vaccination for subgroup 1a and 2a | 
| Antibody concentrations against antigens of MMR vaccine | 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 the 12-month vaccination for subgroup 1a and 2a | 
| Antibody concentrations against antigens of varicella vaccine | 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 the 12-month vaccination for subgroup 1a and 2a | 
| Antibody concentrations above predefined thresholds for antigens of varicella vaccine | % of participants with antibody concentrations ≥ established serostatus cut-off levels for antigens in varicella vaccine | 30 days after the 12-month vaccination for subgroup 1a and 2a | 
| Antibody against meningococcal serogroups A, C, Y, and W | Antibody titers will be measured by hSBA and expressed as geometric mean titers (GMTs) | D0, 30 days after the 6-month age vaccination for group 1 and 2, before and 30 days after the 12-month vaccination for subgroup 1a and 2a, before and after the 15-month vaccination for subgroup 1b | 
| Antibody titers above pre-defined thresholds for meningococcal serogroups A, C, Y, and W | % of participants achieving antibody titers ≥ predefined thresholds, measured by hSBA | 30 days after the 6-month age vaccination for group 1 and 2, before and 30 days after the 12-month vaccination for subgroup 1a and 2a, before and after the 15-month vaccination for subgroup 1b | 

 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