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

• ClinicalTrials.gov Identifier: NCT01890759
• Recruitment Status: Completed
• First Posted: July 2, 2013
• Results First Posted: August 21, 2017
• Last Update Posted: April 19, 2022
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Meningitis; Meningococcal Infection	Biological: Meningococcal Diphtheria Toxoid Vaccine	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 300 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety of a Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine (Menactra®) in Subjects Aged 9 to 23 Months in India and in the Russian Federation
• Actual Study Start Date: June 25, 2013
• Actual Primary Completion Date: April 12, 2016
• Actual Study Completion Date: April 12, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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	Biological: Meningococcal Diphtheria Toxoid Vaccine; 0.5 mL, Intramuscular; Other Name: Menactra®

Outcome Measures

Primary Outcome Measures :

1. 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® [ Time Frame: 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 :

1. 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® [ Time Frame: 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.
2. 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® [ Time Frame: 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.
3. 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® [ Time Frame: 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.
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 Baby Rabbit Complement Before and Following Vaccination With Menactra® [ Time Frame: 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.
5. 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® [ Time Frame: 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.
6. 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® [ Time Frame: 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.
7. 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® [ Time Frame: 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.
8. 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® [ Time Frame: 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.
9. 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® [ Time Frame: 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.
10. 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® [ Time Frame: 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.
11. Serum Bactericidal Assay Using Human Complement Antibody Geometric Mean Titer Ratios of Meningococcal Serogroups A, C, Y, and W-135 Following Vaccination With Menactra® [ Time Frame: 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.
12. 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® [ Time Frame: 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.
13. Percentage of Participants Reporting Solicited Injection Site or Systemic Reactions Following Each Vaccination With Menactra® [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 9 Months to 17 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

India

Vadodara, Gujarat, India, 390022

Kolkata, West Bengal, India, 700017

Lucknow, India, 226003

Vellore, India, 632004

Russian Federation

Murmansk, Russian Federation, 183031

Perm', Russian Federation, 614066

Saint Petersburg, Russian Federation, 197022

Yekaterinburg, Russian Federation, 620028

Sponsors and Collaborators

Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director; Sanofi Pasteur SA

More Information

Additional Information:

Related Info 

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01890759
• Other Study ID Numbers: MTA70; U1111-1122-2171 ( Other Identifier: WHO ); CTRI/2014/12/005272 ( Registry Identifier: Clinical Trials Registry - India )
• First Posted: July 2, 2013
• Results First Posted: August 21, 2017
• Last Update Posted: April 19, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):

Meningitis; Meningococcal Infection; Menactra®

Additional relevant MeSH terms:

Meningococcal Infections; Meningitis; Infections; Neuroinflammatory Diseases; Nervous System Diseases; Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses