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

An Immunogenicity and Safety Evaluation of Menactra® (Meningococcal [Groups A, C, Y and W-135] Polysaccharide Diphtheria Toxoid Conjugate Vaccine) When Administered to Healthy Subjects at 9 Months and Concomitantly With Pentacel® at 15 to 18 Months of Age.

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.

Study Overview

• Status: Completed
• Conditions: Pertussis; Tetanus; Diphtheria; Meningitis; Meningococcal Infection; Haemophilus Influenzae Serotype b (Hib)
• Intervention / Treatment: 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

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 Type: Interventional
• Enrollment (Actual): 1394
• Phase: Phase 4

Contacts and Locations

Study Locations

• Puerto Rico
  • Ponce, Puerto Rico, 00731
  • San Juan, Puerto Rico, 00918
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
    • Pinson, Alabama, United States, 35126
  • Arizona
    • Tucson, Arizona, United States, 85741
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
    • Jonesboro, Arkansas, United States, 72401
    • Little Rock, Arkansas, United States, 72205
  • California
    • Chino, California, United States, 91710
    • Downey, California, United States, 90241
    • La Puente, California, United States, 91744
    • Lakewood, California, United States, 90711
    • Paramount, California, United States, 90723
  • Connecticut
    • Norwich, Connecticut, United States, 06360
  • Georgia
    • Marietta, Georgia, United States, 30062
    • Woodstock, Georgia, United States, 30189
  • Illinois
    • Dekalb, Illinois, United States, 60115
  • Indiana
    • Indianapolis, Indiana, United States, 46256
  • Louisiana
    • Bossier City, Louisiana, United States, 71111
  • Massachusetts
    • Woburn, Massachusetts, United States, 01801
    • Worcester, Massachusetts, United States, 01655
  • Missouri
    • Bridgeton, Missouri, United States, 63044
    • Kansas City, Missouri, United States, 64114
  • Nebraska
    • Elkhorn, Nebraska, United States, 68022
    • Lincoln, Nebraska, United States, 68504
    • Lincoln, Nebraska, United States, 68516
    • Omaha, Nebraska, United States, 68198
  • North Carolina
    • Clyde, North Carolina, United States, 28721
  • North Dakota
    • Fargo, North Dakota, United States, 58103
  • Ohio
    • Cincinnati, Ohio, United States, 45245
    • Fairfield, Ohio, United States, 45014
    • Huber Heights, Ohio, United States, 45424
    • Kettering, Ohio, United States, 45420
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74127
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16505
    • Harleysville, Pennsylvania, United States, 19438
    • Hermitage, Pennsylvania, United States, 16148
    • Scranton, Pennsylvania, United States, 18510
    • Sellersville, Pennsylvania, United States, 18960
  • Tennessee
    • Jackson, Tennessee, United States, 38305
    • Kingsport, Tennessee, United States, 37660
  • Texas
    • Austin, Texas, United States, 78705
    • Dallas, Texas, United States, 75230
    • Fort Worth, Texas, United States, 76107
    • Houston, Texas, United States, 77055
    • Hurst, Texas, United States, 76054
    • San Antonio, Texas, United States, 78229
  • Utah
    • Layton, Utah, United States, 84041
    • Layton, Utah, United States, 84047
    • Murray, Utah, United States, 84107
    • Orem, Utah, United States, 84057
    • Payson, Utah, United States, 84651
    • Roy, Utah, United States, 84067
    • Spanish Fork, Utah, United States, 84660
    • Syracuse, Utah, United States, 84075
  • Virginia
    • Midlothian, Virginia, United States, 23113
  • Washington
    • Spokane, Washington, United States, 99202
    • Spokane, Washington, United States, 99218

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 months to 1 year (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Menactra Vaccine Group; Participants will receive Meningococcal polysaccharide diphtheria toxoid conjugate (Menactra®) at 9 months of age and Menactra® at 15 to 18 months of age.	Biological: Meningococcal polysaccharide diphtheria toxoid conjugate; 0.5 mL, Intramuscular; Other Names: Menactra®
Experimental: Menactra and Pentacel Vaccine Group; 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.	Biological: Meningococcal polysaccharide diphtheria toxoid conjugate + Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed; 0.5 mL, Intramuscular; Other Names: Pentacel®; Menactra®
Active Comparator: Pentacel Vaccine Group; 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.	Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate; 0.5 mL, Intramuscular; Other Names: Pentacel®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Study Participants Achieving Menactra Response for Meningococcal Serogroups A, C, Y, and W-135 Following the 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.	Day 30 post second Menactra vaccination
Geometric Mean Concentrations of Pertussis Vaccine Antibodies Following Vaccination With Either Pentacel Only or Menactra Concomitantly With Pentacel Vaccine	Pertussis antibodies, anti-Pertussis toxoid (PT), Filamentous hemagglutinin (FHA), Pertactin (PRN) antibodies were measured by enzyme-linked immunosorbent assay (ELISA).	Day 30 post-vaccination 2
Percentage of Participants With Pertussis Vaccine Responses Following Vaccination With Either Pentacel Only or Menactra Concomitantly With Pentacel Vaccine	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	Day 30 post-vaccination 2
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	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.	Day 30 post-vaccination 2

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers of Individual Meningococcal Antibodies in Serum Bactericidal Assay With Human Complement (SBA-HC) Analysis Following Vaccination With Menactra Vaccine	Geometric mean titers (GMTs) of antibodies to serogroups A, C, Y, and W-135 were measured by serum bactericidal assay with human complement (SBA HC) before any vaccination and post-vaccination 2	Day 0 (pre-vaccination) and Day 30 post-vaccination 2
Geometric Mean Titers of Individual Antibodies to Filamentous Hemagglutinin, Pertactin, Diphtheria, Tetanus and Polio Antigens Following Vaccination With Either Pentacel Only or Menactra Concomitantly With Pentacel Vaccine	Filamentous hemagglutinin (FHA), Fimbriae types 2 and 3 (FIM), Pertactin (PRN) and anti-Tetanus antibodies were measured by enzyme-linked immunosorbent assay (ELISA); anti-Diphtheria antibodies were measured by a toxin neutralization test.	Day 0 (pre-vaccination) and Day 30 post-vaccination 2
Percentage of Participants Reporting Solicited Injection-site or Systemic Reactions Following Vaccination With Menactra Only, or Pentacel Only or Menactra Concomitantly With Pentacel Vaccine	Solicited injection-site reactions: Tenderness, Erythema, and Swelling. Solicited Systemic Reactions: Fever (Temperature), Vomiting, Abnormal crying, Drowsiness, Loss of appetite, and Irritability. Grade 3 solicited reactions defined as: Tenderness - cries when injected limb is moved, or the movement of the injected limb is reduced; Erythema and Swelling - ≥ 50 mm; Fever > 39.5°C or > 103.1 °F; Vomiting - ≥ 6 episodes per 24 hours or requiring parenteral hydration; Abnormal crying > 3 hours; Drowsiness - Sleeping most of the time or difficult to wake up; Loss of appetite - Refuses ≥ 3 feeds / meals or refuses most feeds / meals; and Irritability - Inconsolable.	Day 0 to Day 7 after any vaccination
Percentage of Participants Reporting Solicited Injection-site or Systemic Reactions Following Vaccination at 9 Months of Age With Menactra Vaccine.	Solicited injection site reactions: Tenderness, Erythema, and Swelling. Solicited Systemic Reactions: Fever (Temperature), Vomiting, Abnormal crying, Drowsiness, Loss of appetite, and Irritability. Grade 3 solicited reactions defined as: Tenderness - cries when injected limb is moved, or the movement of the injected limb is reduced; Erythema and Swelling - ≥ 50 mm; Fever > 39.5°C or > 103.1 °F; Vomiting - ≥ 6 episodes per 24 hours or requiring parenteral hydration; Abnormal crying > 3 hours; Drowsiness - Sleeping most of the time or difficult to wake up; Loss of appetite - Refuses ≥ 3 feeds / meals or refuses most feeds/meals; and Irritability - Inconsolable.	Day 0 to Day 7 after 9-month vaccination
Percentage of Participants Reporting Solicited Injection-site or Systemic Reactions Following Vaccination With Menactra Only, or Pentacel Only, or Menactra Concomitantly With Pentacel Vaccine	Solicited injection site reactions: Tenderness, Erythema, and Swelling. Solicited systemic reactions: Fever (Temperature), Vomiting, Abnormal crying, Drowsiness, Loss of appetite, and Irritability. Grade 3 reactions defined as: Tenderness - cries when injected limb is moved, or the movement of the injected limb is reduced; Erythema and Swelling - ≥ 50 mm; Fever > 39.5°C or > 103.1 °F; Vomiting - ≥ 6 episodes per 24 hours or requiring parenteral hydration; Abnormal crying > 3 hours; Drowsiness - Sleeping most of the time or difficult to wake up; Loss of appetite - Refuses ≥ 3 feeds/meals or refuses most feeds/meals; and Irritability - Inconsolable.	Day 0 to Day 7 after the 15 to 18 month vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: August 2, 2012
• First Submitted That Met QC Criteria: August 3, 2012
• First Posted (Estimate): August 8, 2012

Study Record Updates

• Last Update Posted (Estimate): December 15, 2015
• Last Update Submitted That Met QC Criteria: November 10, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Meningitis; Pertussis; Diphtheria; Menactra®; Meningococcal Infection; Pentacel®
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Corynebacterium Infections; Neisseriaceae Infections; Whooping Cough; Diphtheria; Meningitis; Meningococcal Infections
• Other Study ID Numbers: MTA55; U1111-1120-1368 (Other Identifier: WHO)