Immunogenicity and Safety of Menactra® Vaccine in Subjects Aged 9 to 23 Months in India and in the Russian Federation

Phase 3

Completed

Conditions: Meningococcal Infection
Meningitis

Interventions: Biological: Meningococcal Diphtheria Toxoid Vaccine

Registration Number: NCT01890759

Lead Sponsor: Sanofi Pasteur, a Sanofi Company

Brief Summary: The purpose of this study is to assess the immunogenicity and safety of Menactra® vaccine given as a two-dose series in infants and toddlers.

Primary Objectives:

* To assess the seroprotection rate (percentage of subjects with a serum bactericidal assay using human complement \[SBA-HC\] titer ≥ 1:8) 28 days after the second of 2 doses of Menactra® administered 3 to 6 months apart.

Secondary Objectives:

* To assess the immune responses to meningococcal antigens (serogroups A, C, Y, and W-135) 28 days following the second vaccination with Menactra® using SBA-HC and SBA-BR titers.

* To assess the safety profile of Menactra® after each and any vaccination.

Detailed Description: Study participants will receive 2 doses on Menactra® vaccine at 3 to 6 months apart and will be monitored for safety and immunogenicity.

The planned duration of each subject's participation in the trial will be from 118 to 215 days.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 300

Inclusion Criteria

Male and female subjects aged 9 to 17 months on the day of inclusion
Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative(s) (if applicable)
Subject and parent/legally acceptable representative (if applicable) able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria

Participation in the 4 weeks preceding inclusion 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 each trial vaccination or planned receipt of any vaccine in the 4 weeks following each trial vaccination, except for:
(i) influenza vaccination, which may be received at least 2 weeks before study vaccines.
(ii) measles (M) or measles, mumps, rubella (MMR) routine vaccination, which can be administered concomitantly with the first dose of study vaccine as per routine immunization schedule
(iii) for subjects enrolled at Indian sites: oral poliomyelitis vaccine (OPV) received during National Immunization Days (NIDs) and supplementary immunization activity days (SIADs)
Previous vaccination against meningococcal disease with either the study vaccine or another meningococcal vaccine
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)
History of meningococcal diseases, confirmed either clinically, serologically, or microbiologically
At high risk, in the opinion of the Investigator, for meningococcal disease during the trial
Known or suspected systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances
Known thrombocytopenia, contraindicating intramuscular vaccination
Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination
In an emergency setting, or hospitalized involuntarily
Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion
For subjects enrolled at Indian sites: Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C).
For subjects enrolled at Russian sites: Acute disease of any severity on the day of vaccination or febrile illness (axillary temperature ≥ 37.0°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
Personal history of Guillain-Barré Syndrome.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Meningococcal Diphtheria Toxoid Vaccine	Meningococcal Diphtheria Toxoid Vaccine	Participants at age 9 to 17 months of enrollment will receive 2 doses on Menactra vaccine at 3 to 6 months apart

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving Seroprotection Using a Serum Bactericidal Assay Human Complement With Antibody Titers ≥ 1:8 for Meningococcal Serogroups A, C, Y, and W-135 Before and Following Vaccination With Menactra®	Day 0 (pre-vaccination) and Day 28 post-second vaccination	Functional antibody activity against the meningococcal serogroups A, C, Y, and W-135 antigens contained in Menactra vaccine was measured using a SBA-HC assay. Seroprotection was defined as antibody titers ≥ 1:8.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With At Least Four-Fold Rise in Threshold in Meningococcal Serogroups A, C, Y, and W-135 Antibody Titers by Serum Bactericidal Assay Using Human Complement Following Vaccination With Menactra®	Day 0 (pre-vaccination) and Day 28 post-vaccination	Functional antibody activity against the meningococcal serogroups A, C, Y, and W-135 antigens contained in Menactra vaccine was measured using a SBA-HC assay.
Percentage of Participants Achieving the Threshold Using a Serum Bactericidal Assay Human Complement With Antibody Titers ≥ 1:4 for Meningococcal Serogroups A, C, Y, and W-135 Before and Following Vaccination With Menactra®	Day 0 (pre-vaccination) and Day 28 post-vaccination	Functional antibody activity against the meningococcal serogroups A, C, Y, and W-135 antigens contained in Menactra vaccine was measured using a SBA-HC assay. The threshold was defined as antibody titers ≥ 1:4.
Percentage of Participants Achieving the Threshold in Meningococcal Serogroups A, C, Y, and W-135 Antibody Titers ≥ 1:8 by Serum Bactericidal Assay Using Human Complement Before and Following Vaccination With Menactra®	Day 0 (pre-vaccination) and Day 28 post-vaccination	Functional antibody activity against the meningococcal serogroups A, C, Y, and W-135 antigens contained in Menactra vaccine was measured using a SBA-HC assay. The threshold was defined as antibody titers ≥ 1:8.
Percentage of Participants Achieving the Threshold in Meningococcal Serogroups A, C, Y, and W-135 Antibody Titers ≥ 1:8 by Serum Bactericidal Assay Using Baby Rabbit Complement Before and Following Vaccination With Menactra®	Day 0 (pre-vaccination) and Day 28 post-vaccination	Functional antibody activity against the meningococcal serogroups A, C, Y, and W-135 antigens contained in Menactra vaccine was measured using a SBA-BR assay. The threshold was defined as antibody titers ≥ 1:8.
Percentage of Participants Achieving the Threshold in Meningococcal Serogroups A, C, Y, and W-135 Antibody Titers ≥ 1:4 by Serum Bactericidal Assay Using Baby Rabbit Complement Before and Following Vaccination With Menactra®	Day 0 (pre-vaccination) and Day 28 post-vaccination	Functional antibody activity against the meningococcal serogroups A, C, Y, and W-135 antigens contained in Menactra vaccine was measured using a SBA-BR assay. The threshold was defined as antibody titers ≥ 1:4.
Percentage of Participants Achieving the Threshold in Meningococcal Serogroups A, C, Y, and W-135 Antibody Titers ≥ 1:4 by Serum Bactericidal Assay Using Human Complement Before and Following Vaccination With Menactra®	Day 0 (pre-vaccination) and Day 28 post-vaccination	Functional antibody activity against the meningococcal serogroups A, C, Y, and W-135 antigens contained in Menactra vaccine was measured using a SBA-HC assay. The threshold was defined as antibody titers ≥ 1:4.
Percentage of Participants With At Least Four-Fold Rise in Meningococcal Serogroups A, C, Y, and W-135 Antibody Titers by Serum Bactericidal Assay Using Baby Rabbit Complement Following Vaccination With Menactra®	Day 0 (pre-vaccination) and Day 28 post-vaccination	Functional antibody activity against the meningococcal serogroups A, C, Y, and W-135 antigens contained in Menactra vaccine was measured using a SBA-BR assay.
Serum Bactericidal Assay Using Human Complement Antibody Geometric Mean Titers of Meningococcal Serogroups A, C, Y, and W-135 Before and Following Vaccination With Menactra®	Day 0 (pre-vaccination) and Day 28 post-vaccination	Functional antibody activity against the meningococcal serogroups A, C, Y, and W-135 antigens contained in Menactra vaccine was measured using a SBA-HC assay.
Percentage of Participants Reporting Solicited Injection Site or Systemic Reactions Following Each Vaccination With Menactra®	Day 0 up to Day 7 post-each vaccination	Injection site: Tenderness, Erythema, and Swelling. Systemic: Fever (Temperature), Vomiting, Crying abnormal, Drowsiness, Appetite lost, Irritability. Grade 3 Injection site: Tenderness, Cries when injected limb is moved or the movement of the injected limb is reduced. Erythema and Swelling, ≥50 mm. Grade 3 Systemic: Fever, \>39.5C; Vomiting, ≥6 episodes per 24 hours or requiring parenteral hydration; Crying abnormal, \>3 hours; Drowsiness, Sleeping most of the time or difficult to wake; Appetite lost, Refuses ≥3 feeds/meals or refuses most feeds/meals; Irritability, Inconsolable.
Percentage of Participants With At Least Four-Fold Rise in Threshold Meningococcal Serogroups A, C, Y, and W-135 Antibody Titers by Serum Bactericidal Assay Using Human Complement Following Vaccination With Menactra®	Day 0 (pre-vaccination) and Day 28 post-vaccination	Functional antibody activity against the meningococcal serogroups A, C, Y, and W-135 antigens contained in Menactra vaccine was measured using a SBA-HC assay.
Serum Bactericidal Assay Using Human Complement Antibody Geometric Mean Titer Ratios of Meningococcal Serogroups A, C, Y, and W-135 Following Vaccination With Menactra®	Day 0 (pre-vaccination) and Day 28 post-vaccination	Functional antibody activity against the meningococcal serogroups A, C, Y, and W-135 antigens contained in Menactra vaccine was measured using a SBA-HC assay.
Serum Bactericidal Assay Using Baby Rabbit Complement Geometric Mean Titer Ratios of Meningococcal Serogroups A, C, Y, and W-135 Before and Following Vaccination With Menactra®	Day 0 (pre-vaccination) and Day 28 post-vaccination	Functional antibody activity against the meningococcal serogroups A, C, Y, and W-135 antigens contained in Menactra vaccine was measured using a SBA-BR assay.
Serum Bactericidal Assay Using Baby Rabbit Complement Geometric Mean Titers of Meningococcal Serogroups A, C, Y, and W-135 Before and Following Vaccination With Menactra®	Day 0 (pre-vaccination) and Day 28 post-vaccination	Functional antibody activity against the meningococcal serogroups A, C, Y, and W-135 antigens contained in Menactra vaccine was measured using a SBA-BR.