Study of Menactra® in Healthy Subjects at 9 Months and Concomitantly With Pentacel® at 15 to 18 Months of Age

Phase 4

Completed

• Conditions: Meningococcal Infection; Meningitis; Diphtheria; Tetanus; Pertussis; Haemophilus Influenzae Serotype b (Hib)
• Interventions: Biological: Meningococcal polysaccharide diphtheria toxoid conjugate; Biological: Meningococcal polysaccharide diphtheria toxoid conjugate + Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed; Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate

• Registration Number: NCT01659996
• Lead Sponsor: Sanofi Pasteur, a Sanofi Company

Brief Summary

The aim of the study is to further characterize the safety and immunogenicity of Menactra® in the population \<2 years of age when administered alone and when the second dose is administered concomitantly with the 4th dose of Pentacel®, a licensed pediatric vaccine.

Primary Objectives:

* To evaluate and compare the antibody responses to meningococcal serogroups A, C, Y, and W-135 induced by 2 injections of Menactra® in subjects aged 9 months at the first vaccination visit and 15 to 18 months at the second vaccination visit.

* To evaluate and compare the antibody responses to Pertussis (pertussis toxoid \[PT\], filamentous haemagglutinin \[FHA\] and pertactin \[PRN\]) antigens induced by a dose of Pentacel® when administered concomitantly with Menactra® to those elicited by a dose of Pentacel® administered alone.

* To evaluate and compare the antibody responses to polyribosylribitol phosphate (PRP), tetanus and diphtheria antigens induced by a dose of Pentacel® when administered concomitantly with Menactra® to those elicited by a dose of Pentacel® alone.

Observational Objectives:

* To describe the safety profile (immediate unsolicited AEs within 30 minutes of each trial vaccination, solicited reactions within 7 days of each vaccination, unsolicited AEs within 30 days of each vaccination, and serious adverse events \[SAEs\] throughout the course of the trial from Day 0 up to Day 30 after the last trial vaccination\[s\]) in all trial groups

* To describe the antibody responses to meningococcal serogroups A, C, Y, and W-135, measured by SBA HC, 30 days after the second Menactra® administration

* To describe the antibody responses to Pentacel® (PT, FHA, PRN, FIM, diphtheria, tetanus, polio, PRP) measured by enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), or functional assays.

Detailed Description

Participants will be vaccinated according to their randomized groups at age 9 months and at age 15 to 18 months. They will undergo immunogenicity assessment and safety monitoring post-vaccination.

Study Timeline

• Study Start: 2012-07
• Study First Submitted: 2012-08-02
• Study First Submitted QC: 2012-08-03
• Study First Posted: 2012-08-08
• Primary Completion: 2014-11
• Study Completion: 2015-09
• Results First Submitted: 2015-09-29
• Status Verified: 2015-11
• Results First Submitted QC: 2015-11-10
• Last Update Submitted: 2015-11-10
• Results First Posted: 2015-12-15
• Last Update Posted: 2015-12-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1394

Inclusion Criteria

• Aged 9 months (249 to 305 days) for Groups 1 and 2, or 15 to 18 months (420 to 570 days) for Group 3 on the day of the first trial visit
• Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative
• Received 3 doses of any DTaP-containing vaccines
• Received 3 doses of a Hib-containing vaccine, or 2 doses if the subject received PRP-OMP (PedvaxHIB® or Comvax®[HepB-Hib])
• Received at least 3 doses of a CRM197-based pneumococcal conjugate vaccine (Pneumococcal conjugate vaccine [PCV] or 13-Valent pneumococcal conjugate vaccine [PCV13])
• Subject and parent/ legally acceptable representative are able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria

• Participation 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 each trial vaccination or planned receipt of any vaccine in the 4 weeks following each trial vaccination, except for influenza vaccination, which may be received at least 2 weeks before or after the trial vaccination(s)
• Vaccination against meningococcal disease with either the trial vaccine or another vaccine, or receipt of the 4th dose of any DTaP-containing vaccines, receipt of the 4th dose of a Hib-containing vaccine, or receipt of the 3rd dose of PRP-OMP (PedvaxHIB® or Comvax® [Hep B-Hib]) prior to enrollment or during the conduction of the trial, except for Group 1 subjects, who may receive Hib vaccine at 12 months
• 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). Topical steroids are not included in this exclusion criterion
• History of invasive meningococcal infection, confirmed either clinically, serologically, or microbiologically
• Personal history of Guillain-Barré Syndrome
• History of encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of a previous dose of a pertussis containing vaccine that is not attributable to another identifiable cause
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to one of the vaccines used in the trial or to a vaccine containing any of the same substances
• Known thrombocytopenia, as reported by the parent/ legally acceptable representative, 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
• Moderate or severe acute illness/ infection (according to investigator judgment) or febrile illness (temperature ≥ 100.4°F [≥ 38.0°C]) on the day of vaccination. A prospective subject should not be included in the trial until the condition has resolved or the febrile event has subsided
• Receipt of oral or injectable antibiotic therapy within 72 hours prior to any trial blood draw (topical antibiotics, drops, or ointments are not included in this criterion)
• Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Menactra Vaccine Group	Meningococcal polysaccharide diphtheria toxoid conjugate	Participants will receive Meningococcal polysaccharide diphtheria toxoid conjugate (Menactra®) at 9 months of age and Menactra® at 15 to 18 months of age.
Menactra and Pentacel Vaccine Group	Meningococcal polysaccharide diphtheria toxoid conjugate + Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed	Participants will receive Meningococcal polysaccharide diphtheria toxoid conjugate (Menactra®) at 9 months of age and Menactra® + Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed (Pentacel®) concomitantly at 15 to 18 months of age.
Pentacel Vaccine Group	Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate	Participants will receive only Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Pentacel®) at 15 to 18 months of age.

Primary Outcome Measures

Name	Time	Method
Percentage of Study Participants Achieving Menactra Response for Meningococcal Serogroups A, C, Y, and W-135 Following the Second Menactra Vaccination	Day 30 post second Menactra vaccination	Titers of antibodies to serogroups A, C, Y, and W-135 were measured by serum bactericidal assay using human complement (hSBA or SBA-HC).; Menactra vaccine response defined as subjects with an hSBA titer \<1:8 at baseline achieving an hSBA titer ≥1:8, and subjects with an hSBA titer ≥1:8 at baseline achieving a ≥ 4-fold increase in hSBA titer.
Geometric Mean Concentrations of Pertussis Vaccine Antibodies Following Vaccination With Either Pentacel Only or Menactra Concomitantly With Pentacel Vaccine	Day 30 post-vaccination 2	Pertussis antibodies, anti-Pertussis toxoid (PT), Filamentous hemagglutinin (FHA), Pertactin (PRN) antibodies were measured by enzyme-linked immunosorbent assay (ELISA).
Percentage of Participants With Pertussis Vaccine Responses Following Vaccination With Either Pentacel Only or Menactra Concomitantly With Pentacel Vaccine	Day 30 post-vaccination 2	Pertussis antibodies, anti-Pertussis toxoid (PT), Filamentous hemagglutinin (FHA), and Pertactin (PRN) antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Pertussis response was defined as: ≥4 × baseline concentration, if the anti-pertussis antibody concentration at baseline is \<4 × lower limit of quantification (LLOQ), Or ≥2 × baseline concentration, if the anti-pertussis antibody concentration at baseline is ≥4 × LLOQ
Percentage of Participants With Antibody Responses to Diphtheria, Tetanus and Polyribosylribitol Phosphate Antigens Following Vaccination With Either Pentacel Only or Menactra Concomitantly With Pentacel Vaccine	Day 30 post-vaccination 2	Anti-Tetanus antibodies were measured by enzyme-linked immunosorbent assay (ELISA), anti-polyribosylribitol phosphate (PRP) antibodies were measured using a Farr-type radioimmunoassay, and anti-diphtheria antibodies were measured by a toxin neutralization test.; The vaccine responses were defined as: Anti-PRP antibody concentrations ≥1.0 μg/mL; Anti-tetanus antibody concentrations ≥1.0 IU/mL and Anti-diphtheria antibody concentrations ≥1.0 IU/mL, respectively, 30 days after vaccination with Pentacel® in participants in Groups 2 and 3.