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

Sanofi Pasteur, a Sanofi Company950 enrolled

Overview

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®.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

950

Conditions

Interventions

Meningococcal Polysaccharide (Serogroups A,C,Y and W) Tetanus Toxoid Conjugate vaccine MenACYW conjugate vaccineBIOLOGICAL

Pharmaceutical form:Solution for injection Route of administration: Intramuscular, 0.5 mL

Meningococcal (Groups A, C, Y and W 135) Oligosaccharide Diphtheria CRM197 Conjugate VaccineBIOLOGICAL

Pharmaceutical form: Solution for injection Route of administration: Intramuscular, 0.5 mL

Meningococcal Polysaccharide (serogroups A,C,Y and W-135) Diphtheria Toxoid Conjugate VaccineBIOLOGICAL

Pharmaceutical form: Solution for injection Route of administration: Intramuscular, 0.5 mL

Diphtheria and Tetanus Toxoids and Acellular Pertussis, inactivated Poliovirus and Haemophilus b Conjugate VaccineBIOLOGICAL

Pharmaceutical form:Suspension for injection Route of administration: Intramuscular, 0.5 mL

Diphtheria and Tetanus Toxoids and Acellular Pertussis, Hepatitis B and Inactivated Poliovirus VaccineBIOLOGICAL

Pharmaceutical form: Suspension for injection Route of administration: Intramuscular, 0.5 mL

Haemophilus b Conjugate VaccineBIOLOGICAL

Pharmaceutical form:Solution for injection Route of administration: Intramuscular, 0.5 mL

Pneumococcal 13-valent Conjugate VaccineBIOLOGICAL

Pharmaceutical form: Suspension for injection Route of administration: Intramuscular, 0.5 mL

Rotavirus Vaccine, Live, Oral, PentavalentBIOLOGICAL

Pharmaceutical form:Oral solution Route of administration: Oral, 2 mL

Hepatitis B VaccineBIOLOGICAL

Pharmaceutical form:Suspension for injection Route of administration: Intramuscular, 0.5 mL

Measles, Mumps, and Rubella Virus Vaccine LiveBIOLOGICAL

Pharmaceutical form: Lyophilized live virus vaccine Route of administration: Subcutaneous, 0.5 mL

Varicella Virus Vaccine LiveBIOLOGICAL

Pharmaceutical form:Suspension for injection Route of administration: Subcutaneous, 0.5 mL

Eligibility

Sex: ALLMin age: 6 MonthsMax age: 19 MonthsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Infants Groups 1 and 2: Percentage of Participants With Vaccine Seroresponse Measured by Serum Bactericidal Assay Using Human Complement (hSBA) at 30 Days Post Second Dose of MenACYW Conjugate Vaccine or MENVEO

Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the hSBA. The hSBA vaccine seroresponse was defined as a post-vaccination titer \>= 1:16 for participants with pre-vaccination hSBA titer \< 1:8, or a post-vaccination titer \>= 4-fold increase from baseline for participant with pre-vaccination hSBA titer \>= 1:8.

Time frame: Baseline (Day 0) and 30 days post second dose (12 to 13 MoA) of MenACYW conjugate vaccine or MENVEO, maximum of 14 months

Secondary Outcomes

Infants Groups 1 and 2: Percentage of Participants Who Achieved Antibody Titer (Seroprotection) >=1:8 by hSBA at 30 Days Post Second Dose of MenACYW Conjugate Vaccine or MENVEO

Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the hSBA. Seroprotection rate was defined as percentage of participants with hSBA titers \>= 1:8.

Time frame: At 30 days post second dose (12 to 13 MoA) of MenACYW conjugate vaccine or MENVEO

Infants Groups 1 and 2: Percentage of Participants With hSBA Antibody Titer >= 1:4 and >= 1:8

Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the hSBA. Participants with hSBA titers \>= 1:4 and \>= 1:8 were analyzed. PPAS1= Per-Protocol Analysis Set 1; FAS1= Full analysis set 1; PPAS3= Per-Protocol Analysis Set 3; and FAS3= Full analysis set 3.

Time frame: PPAS1: At 30 days post first dose (6 to 7 MoA); PPAS2: At Baseline (pre-dose on Day 0) and 30 days post second dose (12 to 13 MoA); and PPAS3: At 6 months post first dose (6 to 7 MoA) of MenACYW conjugate vaccine or MENVEO

Infants Groups 1 and 2: Geometric Mean Titers Against Meningococcal Serogroups A, C, W, and Y

Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the hSBA and the results were expressed as geometric mean titers.

Infants Groups 1 and 2: Percentage of Participants With hSBA Antibody Titer >=1:4 to >= 1:128

Infants Groups 1 and 2: Percentage of Participants With hSBA Antibody Titer >= 4-Fold Rise From Pre-Vaccination to Post-Vaccination

Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the hSBA. Participants with hSBA titers \>= 4-fold increase from baseline (pre-vaccination) were analyzed.

Time frame: PPAS1: At 30 days post first dose (6 to 7 MoA); and PPAS2: At 30 days post second dose (12 to 13 MoA) of MenACYW conjugate vaccine or MENVEO

Infants Groups 1 and 2: Percentage of Participants With Vaccine Seroresponse Measured by hSBA at 30 Days Post First Dose of MenACYW Conjugate Vaccine or MENVEO

Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the hSBA. Participants with hSBA vaccine seroresponse which was defined as \>= 4-fold increase from baseline (pre-vaccination) were analyzed.

Time frame: At 30 days post first dose (6 to 7 MoA) of MenACYW conjugate vaccine or MENVEO

Toddlers Groups 3 and 4: Percentage of Participants With hSBA Antibody Titer >= 1:4 and >= 1:8

Time frame: Baseline (Day 0) and 30 days post second dose (20 to 23 MoA) of MenACYW conjugate vaccine or Menactra

Toddlers Groups 3 and 4: Geometric Mean Titers Against Meningococcal Serogroups A, C, W, and Y

Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the hSBA and the results were expressed as geometric mean titers.

Time frame: Baseline (Day 0) and 30 days post second dose (20 to 23 MoA) of MenACYW conjugate vaccine or Menactra

Toddlers Groups 3 and 4: Percentage of Participants With hSBA Antibody Titer >= 1:4 to >= 1:128

Time frame: Baseline (Day 0) and at 30 days post second dose (20 to 23 MoA) of MenACYW conjugate vaccine or Menactra

Toddlers Groups 3 and 4: Percentage of Participants With hSBA Antibody Titer >= 4-Fold Rise From Pre-Vaccination to Post-Vaccination

Time frame: At 30 days post second dose (20 to 23 MoA) of MenACYW conjugate vaccine or Menactra

Toddlers Groups 3 and 4: Percentage of Participants With Vaccine Seroresponse Measured by hSBA at 30 Days Post Second Dose of MenACYW Conjugate Vaccine or Menactra