Concomitant Administration of a New Hexavalent Vaccine With a Meningococcal Serogroup C Conjugate Vaccine in Healthy Infants During Primary Series Immunisation Followed by Booster Vaccination

Study Overview
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Brief Summary
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Primary Series Primary objectives To demonstrate that the concomitant administration of the hexavalent vaccine with a meningococcal serogroup C conjugate vaccine is non inferior to the administration of the hexavalent vaccine without a MenC vaccine concomitantly in term of seroprotection rate for hepatitis B one month after the third dose of the hexavalent vaccine To demonstrate that the concomitant administration of a MenC vaccine with the hexavalent vaccine induces an acceptable response for MenC in term of seroprotection rate (SPR) one month after the second dose of MenC Booster Primary objectives - To describe the immunogenicity of a booster dose of the hexavalent vaccine and of a meningococcal group ACWY conjugate (MenACWY) vaccine either co-administered at 12 months of age or given separately.

Detailed Description
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Primary Series Secondary objectives To describe the antibody response to all the hexavalent vaccine antigens one month after the third dose of the hexavalent vaccine when given concomitantly or not to MenC To describe the antibody response to MenC vaccine when a MenC vaccine is given concomitantly with the hexavalent vaccine, one month after the first and the second dose of MenC vaccine To describe the safety profile of the hexavalent vaccine after each and any injection when given concomitantly or not with a MenC vaccine Booster Secondary objectives To describe the antibody (Ab) persistence at 12 months of age for the hexavalent valences following a 3-dose primary vaccination at 2, 3 and 4 months of age (prior to administration of a booster dose) To describe the safety of a booster dose of the hexavalent vaccine and of a meningococcal group ACWY conjugate (MenACWY) vaccine either co-administered at 12 months of age or given separately.

Official Title
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A Phase III Open-label Randomised Study to Evaluate the Immunogenicity and Safety of the Concomitant Administration of a New Hexavalent DTaP-IPV-HepB-PRP-T Combined Vaccine (Hexavalent Vaccine) Given at 2, 3, and 4 Months of Age With a Meningococcal Serogroup C Conjugate (MenC) Vaccine Given at 2 and 4 Months of Age

Conditions
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Virus Diseases, Neisseria Meningitidis, Bacterial Infections

Intervention / Treatment
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* Biological: Hexavalent vaccine
* Biological: NeisVac-C
* Biological: Prevenar 13
* Biological: RotaTeq
* Biological: Nimenrix
* Biological: M-M-RVAXPRO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy infant 46 to 74 days of age (both inclusive) Born at full term of pregnancy (≥37 weeks) and/or with a birth weight≥2.5 kg Subject's parent(s) or legal representative able to comply with the study procedures Exclusion Criteria: Participation in another clinical study investigating a vaccine, drug, medical device, or medical procedure Receipt of any vaccine in the 4 weeks preceding each study vaccination Previous vaccination against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, Haemophilus influenzae type b, meningococcal, pneumococcal, rotavirus infection Know or suspected congenital, hereditary or acquired immunodeficiency History of seizures or encephalopathy Known thrombocytopenia Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular injection Chronic illness that could interfere with trial conduct or completion Known or suspected hypersensitivity to any of the study vaccines' active substance or excipients or history of a life-threatening reaction to a vaccine(s) containing the same substances as the study vaccines Contraindication to any of the study vaccines Known personal or maternal history of hepatitis B or hepatitis C seropositivity History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, Haemophilus influenzae type b or meningococcal serogroup C infection Receipt of immune globulin, blood or blood-derived products, immunosuppressive drugs, systemic corticosteroid since birth Identified as a natural or adopted child of the investigator or employee with direct involvement in the current study.

Ages Eligible for Study
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Minimum Age: 46 Days
Maximum Age: 76 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br> | Biological: Hexavalent vaccine<br>* 0.5 mL intramuscular injection at 2, 3 and 4 months of age (primary series) 0.5 mL intramuscular injection at 12 or 13 months of age (booster)<br>* Other names: poliomyelitis and Haemophilus influenzae type b conjugate vaccine (adsorbed).;Biological: NeisVac-C<br>* 0.5 mL intramuscular injection at 2 and 4 months of age<br>* Other names: Meningococcal group C polysaccharide conjugate vaccine adsorbed;Biological: Prevenar 13<br>* 0.5 mL intramuscular injection at 2 and 4 months of age (primary series) 0.5 mL intramuscular injection at 13 months of age (booster)<br>* Other names: Pneumococcal conjugate vaccine (13-valent, adsorbed);Biological: RotaTeq<br>* 2 mL oral administration at 2, 3 and 4 months<br>* Other names: Human-bovine rotavirus reassortants (live) vaccine;Biological: Nimenrix<br>* 0.5 mL intramuscular injection at 12 months<br>* Other names: Meningococcal group A, C, W-135 and Y conjugate vaccine;Biological: M-M-RVAXPRO<br>* 0.5 mL intramuscular or subcutaneous injection at 13 months of age<br>* Other names: Measles, mumps and rubella vaccine (live);|
| Active Comparator: Group 2<br> | Biological: Hexavalent vaccine<br>* 0.5 mL intramuscular injection at 2, 3 and 4 months of age (primary series) 0.5 mL intramuscular injection at 12 or 13 months of age (booster)<br>* Other names: poliomyelitis and Haemophilus influenzae type b conjugate vaccine (adsorbed).;Biological: Prevenar 13<br>* 0.5 mL intramuscular injection at 2 and 4 months of age (primary series) 0.5 mL intramuscular injection at 13 months of age (booster)<br>* Other names: Pneumococcal conjugate vaccine (13-valent, adsorbed);Biological: RotaTeq<br>* 2 mL oral administration at 2, 3 and 4 months<br>* Other names: Human-bovine rotavirus reassortants (live) vaccine;Biological: Nimenrix<br>* 0.5 mL intramuscular injection at 12 months<br>* Other names: Meningococcal group A, C, W-135 and Y conjugate vaccine;Biological: M-M-RVAXPRO<br>* 0.5 mL intramuscular or subcutaneous injection at 13 months of age<br>* Other names: Measles, mumps and rubella vaccine (live);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with an anti-hepatitis B concentration ≥10 IU/mL |  | Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine) | 
| Proportion of subjects with an anti-MenC titre ≥1:8 dil |  | Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with an anti-polyribosylribitol phosphate concentration ≥0.15 µg/mL |  | Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine), Month 12 (Pre-booster) and Month 13 (One month post-booster) | 
| Proportion of subjects with an anti-diphtheria concentration ≥0.01 IU/mL |  | Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine), Month 12 (Pre-booster) | 
| Proportion of subjects with an anti-tetanus concentration ≥0.01 IU/mL |  | Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine), Month 12 (Pre-booster) | 
| Proportion of subjects with an anti-inactivated poliovirus 1, 2, 3 titre ≥1:8 dil |  | Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine), Month 12 (Pre-booster) and Month 13 (One month post-booster) | 
| Proportion of subjects with pertussis vaccine response |  | Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine) | 
| Proportion of subjects with an anti-MenC titre ≥1:8 dil |  | Month 3 (One month after dose 1 of MenC vaccine) | 
| Solicited injection-site and systemic reactions |  | Day 1 to Day 7 following vaccination | 
| Unsolicited adverse events |  | Day 1 to Day 30 following vaccination | 
| Serious adverse events |  | From signature of the informed consent to the last visit of the subject, an expected average of 11 months | 
| Proportion of subjects with an anti-polyribosylribitol phosphate concentration ≥1 µg/mL |  | Month 12 (Pre-booster) and Month 13 (One month post-booster) | 
| Proportion of subjects with an anti-diphtheria concentration ≥0.1 IU/mL |  | Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine), Month 12 (Pre-booster) and Month 13 (One month post-booster) | 
| Proportion of subjects with an anti-tetanus concentration ≥0.1 IU/mL |  | Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine), Month 12 (Pre-booster) and Month 13 (One month post-booster) | 
| Proportion of subjects with an anti-MenA, anti-MenC, anti-MenW-135, anti-MenY titre ≥1:8 dil |  | Month 13 (One month after MenAWCY vaccine) | 
| Proportion of subjects with an anti-hepatitis B concentration ≥10 IU/mL |  | Month 12 (Pre-booster) and Month 13 (One month post-booster) | 
| Proportion of subjects with pertussis booster response |  | Month 13 (One month post-booster) |