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

Study Overview
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Brief Summary
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The primary objective of this study is to demonstrate the non-inferiority of the vaccine seroresponse to meningococcal serogroups A, C, Y, and W following administration of 2 doses of MenACYW conjugate vaccine compared to 2 doses of MENVEO® when given concomitantly with routine pediatric vaccines to infants and toddlers 6 to 7 months of age and 12 to 13 months of age. The secondary objectives of the study are: To demonstrate the non-inferiority of the percentage of participants with antibody titers to meningococcal serogroups A, C, Y, and W ≥ 1:8 following administration of 2 doses of MenACYW conjugate vaccine compared to 2 doses of MENVEO® when given concomitantly with pediatric routine vaccines to infants and toddlers at 6 to 7 months of age and 12 to 13 months of age. To describe the antibody response against meningococcal serogroups A, C, Y, and W 30 days after the second vaccination at 12 to 13 months of age with MenACYW conjugate vaccine or MENVEO®. To describe the antibody response against meningococcal serogroups A, C, Y, and W 30 days and 6 months after the first vaccination at 6 to 7 months of age with MenACYW conjugate vaccine or MENVEO®. To describe the antibody response against meningococcal serogroups A, C, Y, and W 30 days after the second vaccination at 20 to 23 months of age with MenACYW conjugate vaccine or Menactra®.

Detailed Description
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Study duration per participant is approximately 1 year in Group 1 and Group 2, and 10 months in Group 3 and Group 4. This duration includes a safety follow-up contact at 6 months after the last vaccination.

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

Conditions
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Healthy Volunteers (Meningococcal Infection)

Intervention / Treatment
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* Biological: Meningococcal Polysaccharide (Serogroups A,C,Y and W) Tetanus Toxoid Conjugate vaccine MenACYW conjugate vaccine
* Biological: Meningococcal (Groups A, C, Y and W 135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine
* Biological: Meningococcal Polysaccharide (serogroups A,C,Y and W-135) Diphtheria Toxoid Conjugate Vaccine
* Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis, inactivated Poliovirus and Haemophilus b Conjugate Vaccine
* Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis, Hepatitis B and Inactivated Poliovirus Vaccine
* Biological: Haemophilus b Conjugate Vaccine
* Biological: Pneumococcal 13-valent Conjugate Vaccine
* Biological: Rotavirus Vaccine, Live, Oral, Pentavalent
* Biological: Hepatitis B Vaccine
* Biological: Measles, Mumps, and Rubella Virus Vaccine Live
* Biological: Varicella Virus Vaccine Live


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Aged 6 to 7 months (168 to 224 days) or 17 to 19 months on the day of the first visit Informed consent form has been signed and dated by the parent(s) or other guardian and by an independent witness if required by local regulations Subject and parent/guardian are able to attend all scheduled visits and to comply with all trial procedures For subjects 6 to 7 months of age at enrollment (Group 1 and Group 2), documented history of having received 2 doses of diphtheria, tetanus and acellular pertussis (DTaP), Haemophilus influenza type B (Hib), inactivated poliovirus (IPV), pneumococcal, hepatitis B (for children who received hepatitis B at 2 and 4 months of age, prior receipt of 3 doses of hepatitis B), and rotavirus vaccines For subjects to be enrolled at 17 to 19 months of age (Group 3 and Group 4), documented history of having received all routine pediatric vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) up to the age of enrollment 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 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, polysaccharide, or conjugate meningococcal vaccine containing serogroups A, C, Y, or W; or meningococcal B serogroup-containing vaccine) For subjects to be enrolled at 6 to 7 months of age (Group 1 and Group 2), prior receipt of more than 2 doses of rotavirus vaccine (Rotateq), DTaP, Hib, IPV, pneumococcal, hepatitis B (for children who received hepatitis B at 2 and 4 months of age, prior receipt of more than 3 doses of hepatitis B vaccine) For subjects to be enrolled at 6 to 7 months of age (Group 1 and Group 2), receipt of the 2 doses of rotavirus vaccine at 2 and 4 months of age Receipt of immune globulins, blood, or blood-derived products in the past 3 months Known or suspected congenital or acquired immunodeficiency or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks) within the past 3 months 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 Arthus-type hypersensitivity reaction after a previous dose of tetanus toxoid-containing vaccine 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 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 subject 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: 6 Months
Maximum Age: 19 Months

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 + routine pediatric vaccines at 6 to 7 months of age and 12 to 13 months of age | Biological: Meningococcal Polysaccharide (Serogroups A,C,Y and W) Tetanus Toxoid Conjugate vaccine MenACYW conjugate vaccine<br>* Pharmaceutical form:Solution for injection Route of administration: Intramuscular, 0.5 mL<br>Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis, inactivated Poliovirus and Haemophilus b Conjugate Vaccine<br>* Pharmaceutical form:Suspension for injection Route of administration: Intramuscular, 0.5 mL<br>Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis, Hepatitis B and Inactivated Poliovirus Vaccine<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular, 0.5 mL<br>Biological: Haemophilus b Conjugate Vaccine<br>* Pharmaceutical form:Solution for injection Route of administration: Intramuscular, 0.5 mL<br>Biological: Pneumococcal 13-valent Conjugate Vaccine<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular, 0.5 mL<br>Biological: Rotavirus Vaccine, Live, Oral, Pentavalent<br>* Pharmaceutical form:Oral solution Route of administration: Oral, 2 mL<br>Biological: Hepatitis B Vaccine<br>* Pharmaceutical form:Suspension for injection Route of administration: Intramuscular, 0.5 mL<br>Biological: Measles, Mumps, and Rubella Virus Vaccine Live<br>* Pharmaceutical form: Lyophilized live virus vaccine Route of administration: Subcutaneous, 0.5 mL<br>Biological: Varicella Virus Vaccine Live<br>* Pharmaceutical form:Suspension for injection Route of administration: Subcutaneous, 0.5 mL<br>|
| Active Comparator: Group 2<br>MENVEO® + routine pediatric vaccines at 6 to 7 months of age and 12 to 13 months of age | Biological: Meningococcal (Groups A, C, Y and W 135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine<br>* Pharmaceutical form: Solution for injection Route of administration: Intramuscular, 0.5 mL<br>Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis, inactivated Poliovirus and Haemophilus b Conjugate Vaccine<br>* Pharmaceutical form:Suspension for injection Route of administration: Intramuscular, 0.5 mL<br>Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis, Hepatitis B and Inactivated Poliovirus Vaccine<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular, 0.5 mL<br>Biological: Haemophilus b Conjugate Vaccine<br>* Pharmaceutical form:Solution for injection Route of administration: Intramuscular, 0.5 mL<br>Biological: Pneumococcal 13-valent Conjugate Vaccine<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular, 0.5 mL<br>Biological: Rotavirus Vaccine, Live, Oral, Pentavalent<br>* Pharmaceutical form:Oral solution Route of administration: Oral, 2 mL<br>Biological: Hepatitis B Vaccine<br>* Pharmaceutical form:Suspension for injection Route of administration: Intramuscular, 0.5 mL<br>Biological: Measles, Mumps, and Rubella Virus Vaccine Live<br>* Pharmaceutical form: Lyophilized live virus vaccine Route of administration: Subcutaneous, 0.5 mL<br>Biological: Varicella Virus Vaccine Live<br>* Pharmaceutical form:Suspension for injection Route of administration: Subcutaneous, 0.5 mL<br>|
| Experimental: Group 3<br>MenACYW conjugate vaccine at 17 to 19 months of age and 20 to 23 months of age | Biological: Meningococcal Polysaccharide (Serogroups A,C,Y and W) Tetanus Toxoid Conjugate vaccine MenACYW conjugate vaccine<br>* Pharmaceutical form:Solution for injection Route of administration: Intramuscular, 0.5 mL<br>|
| Active Comparator: Group 4<br>Menactra® at 17 to 19 months of age and 20 to 23 months of age | Biological: Meningococcal Polysaccharide (serogroups A,C,Y and W-135) Diphtheria Toxoid Conjugate Vaccine<br>* Pharmaceutical form: Solution for injection Route of administration: Intramuscular, 0.5 mL<br>|

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 | Antibody titers are measured by serum bactericidal assay using human complement (hSBA) | 30 days after the second dose of meningococcal vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody titers ≥ 1:8 against meningococcal serogroups A, C,Y, and W 30 days after the second dose of meningococcal vaccine | Percentage of participants achieving antibody titers ≥ predefined threshold of 1:8 | 30 days after the second dose of meningococcal vaccine | 
| Percentage of subjects with titer ≥ 4-fold rise from pre-vaccination to post-vaccination 30 days after the second of dose of meningococcal vaccine |  | 30 days after the second dose of meningococcal vaccine | 
| Antibody titers against meningococcal serogroups A, C, Y, and W 30 days after the first dose of meningococcal vaccine |  | 30 days after the first dose of meningococcal vaccine | 
| Percentage of participants with titer ≥ 4-fold rise from pre-vaccination to post-vaccination 30 days after the first dose of meningococcal vaccine |  | 30 days after the first dose of meningococcal vaccine | 
| Percentage of participants with hSBA vaccine seroresponse 30 days after the first dose of meningococcal vaccine | The hSBA vaccine seroresponse for serogroups A, C, Y, and W is defined as post-vaccination hSBA titers >=1:16 for participants with pre-vaccination titers <1:8 or at least a 4-fold increase in post-vaccination hSBA titers from pre- to post-vaccination, for participants with pre-vaccination titers >=1:8 | 30 days after the first dose of meningococcal vaccine | 
| Antibody titers against meningococcal serogroups A, C, Y, and W 6 months after the first dose of meningococcal vaccine |  | 6 months after the first dose of meningococcal vaccine | 
| Percentage of participants with titer ≥ 4-fold rise from pre-vaccination to post-vaccination 6 months after the first dose of meningococcal vaccine |  | 6 months after the first dose of meningococcal vaccine | 
| Percentage of participants with hSBA vaccine seroresponse 6 months after the first dose of meningococcal vaccine | The hSBA vaccine seroresponse for serogroups A, C, Y, and W is defined as post-vaccination hSBA titers >=1:16 for participants with pre-vaccination titers <1:8 or at least a 4-fold increase in post-vaccination hSBA titers from pre- to post-vaccination, for participants with pre-vaccination titers >=1:8 | 6 months after the first dose of meningococcal vaccine | 
| Antibody titers against meningococcal serogroups A, C, Y, and W 30 days after the second dose of meningococcal vaccine |  | 30 days after the second dose of meningococcal vaccine | 
| Percentage of participants with titer ≥ 4-fold rise from pre-vaccination to post-vaccination 30 days after the second dose of meningococcal vaccine |  | 30 days after the second dose of meningococcal vaccine | 
| Percentage of participants with hSBA vaccine seroresponse 30 days after the second dose of meningococcal vaccine | The hSBA vaccine seroresponse for serogroups A, C, Y, and W is defined as post-vaccination hSBA titers >=1:16 for participants with pre-vaccination titers <1:8 or at least a 4-fold increase in post-vaccination hSBA titers from pre- to post-vaccination, for participants with pre-vaccination titers >=1:8 | 30 days after the second 30 days after the second dose of meningococcal vaccine |