Immunogenicity and Safety of Pediatric Vaccines When Administered With Menactra® in Healthy Toddlers

An Immunogenicity, Safety, and Non-Interference Evaluation of Pediatric Vaccines Administered Concomitantly With Menactra® (Meningococcal [Groups A, C, Y and W-135] Polysaccharide Diphtheria Toxoid Conjugate Vaccine) to Healthy Toddlers

This is a modified single-blind, randomized, parallel-group, comparative, multicenter study to test Menactra vaccine in toddlers.

Primary Objectives:

• To evaluate the antibody responses induced by Measles, Mumps, Rubella, and Varicella (MMRV) vaccine when administered alone or concomitantly with Menactra vaccine.
• To evaluate the antibody responses induced by Pneumococcal Conjugated Vaccine (PCV) when administered alone or concomitantly with Menactra vaccine.

Observational Objectives:

Safety - To describe the safety profile throughout the course of the study from Day 0 up to 6 months after the last study vaccination[s]) in subjects in the study groups.

Immunogenicity:

- To describe the antibody responses to meningococcal serogroups A, C, Y, and W-135, 30 days after the first and second Menactra vaccine administration in a subset of subjects in the first study group.

Study Overview

• Status: Completed
• Conditions: Measles; Rubella; Mumps; Varicella; Meningococcal Meningitis
• Intervention / Treatment: Biological: Meningococcal Polysaccharide Diphtheria Conjugate Vaccine; Biological: Meningococcal Polysaccharide Diphtheria Conjugate Vaccine; Biological: Meningococcal Polysaccharide Diphtheria Conjugate Vaccine; Biological: Measles, Mumps, Rubella and Varicella

Detailed Description

No meningococcal vaccine is presently licensed for the population aged < 2 years in the US, establishing the effectiveness of a quadrivalent polysaccharide conjugate vaccine against invasive meningococcal disease in children aged < 2 years would address this important, currently unmet public health need.

At enrollment, each 9-month old subject will be randomly assigned to a study group and vaccinated. A second vaccination will be administered at 12 months of age. Subjects will provide one blood sample during the trial.

Twelve-month old subjects will also be vaccinated with routine pediatric vaccines and provide one blood sample 30 days after vaccinations in the control group

• Study Type: Interventional
• Enrollment (Actual): 1664
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00918
• United States
  • Alabama
    • Tuscaloosa, Alabama, United States, 35401
  • Arizona
    • Tucson, Arizona, United States, 85741
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
    • Little Rock, Arkansas, United States, 72205
  • California
    • Atascadero, California, United States, 93422
    • Fresno, California, United States, 93726
    • Paramount, California, United States, 90723
    • Roseville, California, United States, 95661
    • Sacramento, California, United States, 95823
    • San Jose, California, United States, 95119
    • Torrance, California, United States, 90502
  • Colorado
    • Aurora, Colorado, United States, 80012
  • Connecticut
    • Norwich, Connecticut, United States, 06360
  • Florida
    • Viera, Florida, United States, 32940
    • West Palm Beach, Florida, United States, 33409
  • Georgia
    • Dalton, Georgia, United States, 30721
    • Marietta, Georgia, United States, 30062
    • Tifton, Georgia, United States, 31794
    • Woodstock, Georgia, United States, 30189
  • Illinois
    • Chicago, Illinois, United States, 60614
    • Chicago, Illinois, United States, 60647
  • Indiana
    • Fishers, Indiana, United States, 46038
  • Iowa
    • Dubuque, Iowa, United States, 52002
    • Dubuque, Iowa, United States, 52001
  • Kentucky
    • Owensboro, Kentucky, United States, 42303
  • Louisiana
    • Bossier City, Louisiana, United States, 71111
  • Maryland
    • Perry Hall, Maryland, United States, 21128
  • Massachusetts
    • Woburn, Massachusetts, United States, 01801
  • Michigan
    • Niles, Michigan, United States, 49120
    • Stevensville, Michigan, United States, 49127
  • Missouri
    • Bridgeton, Missouri, United States, 63044
    • Kansas City, Missouri, United States, 64108
    • St. Charles, Missouri, United States, 63303
    • St. Louis, Missouri, United States, 63104
  • Nebraska
    • Bellevue, Nebraska, United States, 68123
    • La Vista, Nebraska, United States, 68128
    • Omaha, Nebraska, United States, 68131
    • Omaha, Nebraska, United States, 68124
    • Omaha, Nebraska, United States, 68132
    • Omaha, Nebraska, United States, 68117
  • Nevada
    • Henderson, Nevada, United States, 89105
  • New Jersey
    • Whitehouse Station, New Jersey, United States, 08889
  • New York
    • Brooklyn, New York, United States, 11201
    • Fishkill, New York, United States, 12524
    • Hopewell Junction, New York, United States, 12533
    • Ithaca, New York, United States, 14850
    • Lake Success, New York, United States, 11021
    • Mineola, New York, United States, 11501
    • New York, New York, United States, 10016
    • Poughkeepsie, New York, United States, 12603
    • Syracuse, New York, United States, 13210
  • North Carolina
    • Boone, North Carolina, United States, 28607
    • Clyde, North Carolina, United States, 28721
    • Durham, North Carolina, United States, 27705
    • Durham, North Carolina, United States, 27704
  • Ohio
    • Beachwood, Ohio, United States, 44122
    • Cleveland, Ohio, United States, 44195
    • Cleveland, Ohio, United States, 44121
    • Independence, Ohio, United States, 44131
    • Strongsville, Ohio, United States, 44136
  • Pennsylvania
    • Harleysville, Pennsylvania, United States, 19438
    • Hershey, Pennsylvania, United States, 17033
    • Pittsburgh, Pennsylvania, United States, 15220
    • Sellersville, Pennsylvania, United States, 18960
    • Wexford, Pennsylvania, United States, 15090
  • Tennessee
    • Clarksville, Tennessee, United States, 37043
    • Kingsport, Tennessee, United States, 37660
  • Texas
    • Houston, Texas, United States, 77004
    • Longview, Texas, United States, 75605
    • San Antonio, Texas, United States, 78229
    • San Antonio, Texas, United States, 78205
  • Utah
    • Lehi, Utah, United States, 84043
    • Ogden, Utah, United States, 84405
    • Pleasant Grove, Utah, United States, 84062
    • Provo, Utah, United States, 84604
    • South Jordan, Utah, United States, 84095
    • Springville, Utah, United States, 84663
    • St. George, Utah, United States, 84790
    • Urem, Utah, United States, 84057
  • Virginia
    • Charlottesville, Virginia, United States, 22903
    • Charlottesville, Virginia, United States, 22902
    • Charlottesville, Virginia, United States, 22911
    • Midlothian, Virginia, United States, 23113
    • Richmond, Virginia, United States, 23219
  • West Virginia
    • Huntington, West Virginia, United States, 25701
    • Morgantown, West Virginia, United States, 26506
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449

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 :

• Healthy, as determined by medical history and physical examination
• Aged 9 months (249 to 291 days) for Groups 1, 2, and 3 or aged 12 months (365 to 386 days) for Group 4 at the time of enrollment
• The parent or legal guardian has signed and dated the Institutional Review Board (IRB)-approved informed consent form.

Exclusion Criteria :

• Serious acute or chronic disease (e.g., cardiac, renal, metabolic, rheumatologic, psychiatric, hematologic, autoimmune disorders, diabetes, atopic conditions, congenital defects, convulsions, encephalopathy, blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic system, acute untreated tuberculosis) that could interfere with trial conduct or completion
• Known or suspected impairment of immunologic function
• Acute medical illness within the last 72 hours or a temperature ≥ 100.4ºF (≥38.0ºC) at the time of enrollment.
• History of documented invasive meningococcal disease or previous meningococcal vaccination.
• Known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C seropositivity as reported by the parent or legal guardian
• Received either immune globulin or other blood products within the last 3 months, or received injected or oral corticosteroids, or other immunomodulator therapy within 6 weeks of the study vaccines. Individuals on a tapering dose schedule of oral steroids lasting < 7 days and individuals (e.g., asthmatics) on a short schedule of oral steroids lasting 3 to 4 days may be included in the trial as long as they have not received more than one course within the last two weeks prior to enrollment. Topical steroids are not included in this exclusion criterion.
• Anticipated to receive oral or injected antibiotic therapy within the 72 hours prior to any blood draw. Topical antibiotics and antibiotic drops are not included in this exclusion criterion.
• Suspected or known hypersensitivity to any of the vaccine components or history of a life-threatening reaction to the study vaccines or a vaccine containing the same substances. For ProQuad vaccine recipients, this includes a hypersensitivity to gelatin or a history of anaphylactic reactions to neomycin.
• Thrombocytopenia or a bleeding disorder contraindicating intramuscular (IM) vaccination.
• Parent or legal guardian unable or unwilling to comply with the study procedures
• Participation in another interventional clinical trial in the 30 days preceding enrollment or planned participation in another clinical trial involving the investigation of a drug, vaccine, medical procedure, or medical device during the subject's trial period.
• Diagnosed with any condition, which, in the opinion of the investigator, would pose a health risk to the subject or interfere with the evaluation of the vaccine
• Received any vaccine in the 30-day period prior to receipt of the study vaccines, or scheduled to receive any vaccination other than influenza vaccination and hyposensitization therapy in the 30-day period after receipt of the study vaccines. Hyposensitization therapy and influenza vaccination may be received up to two weeks before or two weeks after receiving the study vaccines. Subjects should not have received their fourth dose of Pneumococcal conjugate vaccine (PCV) or Haemophilus influenzae type b (Hib) vaccine or their first dose of Measles, mumps, rubella, varicella (MMRV) vaccine before enrollment or been scheduled to receive these vaccines outside of the study-specified visits.
• Personal or family history of Guillain-Barré Syndrome (GBS)
• History of seizures, including febrile seizures, or any other neurologic disorder
• Known hypersensitivity to dry natural rubber latex.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Menactra® at 9 and 12 Months; Participants will received Menactra® vaccination at 9 and 12 months of age.	Biological: Meningococcal Polysaccharide Diphtheria Conjugate Vaccine; 0.5 mL dose, intramuscular (IM); Other Names: Menactra®; Biological: Meningococcal Polysaccharide Diphtheria Conjugate Vaccine; 0.5 mL dose, IM; Other Names: Menactra®; Biological: Meningococcal Polysaccharide Diphtheria Conjugate Vaccine; 0.5 Ml dose, IM; Other Names: Menactra®
Experimental: Menactra® at 9 Months and Menactra® + MMRV at 12 Months; Participants will receive Menactra® at 9 months of age and Menactra® plus measles, mumps, rubella, varicella (MMRV) vaccine at 12 months of age	Biological: Meningococcal Polysaccharide Diphtheria Conjugate Vaccine; 0.5 mL dose, intramuscular (IM); Other Names: Menactra®; Biological: Meningococcal Polysaccharide Diphtheria Conjugate Vaccine; 0.5 mL dose, IM; Other Names: Menactra®; Biological: Meningococcal Polysaccharide Diphtheria Conjugate Vaccine; 0.5 Ml dose, IM; Other Names: Menactra®
Experimental: Menactra® at 9 Months and Menactra® + PCV at 12 Months; Participants will receive Menactra® at 9 months of age and Menactra® plus pneumococcal conjugate vaccine (PCV) at 12 months of age	Biological: Meningococcal Polysaccharide Diphtheria Conjugate Vaccine; 0.5 mL dose, intramuscular (IM); Other Names: Menactra®; Biological: Meningococcal Polysaccharide Diphtheria Conjugate Vaccine; 0.5 mL dose, IM; Other Names: Menactra®; Biological: Meningococcal Polysaccharide Diphtheria Conjugate Vaccine; 0.5 Ml dose, IM; Other Names: Menactra®
Active Comparator: MMRV + PCV at 12 Months; Participants who received no vaccination at 9 months of age and measles, mumps, rubella, varicella (MMRV) vaccine plus pneumococcal conjugate vaccine (PCV) at 12 months of age	Biological: Measles, Mumps, Rubella and Varicella; 0.5 mL dose, SC; Other Names: M-M-R®II; ProQuad®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measles, Mumps, Rubella, and Varicella (MMRV) Antibody Values in Participants Who Received MMRV Vaccine (Groups 2 and 4 Only)	Percentage of participants who had a concentration of ≥ 300 mIU/mL in the enzyme-linked immunosorbent assay (ELISA) or ≥ 120 mIU/mL in the neutralization when the ELISA concentration was less than 300 mIU/mL - for measles; ≥ 500 U/mL (ELISA) or ≥ 60 (1/dil) in the neutralization assay when the ELISA concentration was less than 500 mIU/mL - for mumps; ≥ 10 IU/mL (ELISA) - for Rubella; and ≥ 300 mIU/mL (ELISA) or ≥ 4 (1/dil) Fluorescent antibody to membrane antigen (FAMA) when the ELISA concentration was less than 300 mIU/mL - for varicella.	Day 30 after the 12-month vaccination
Geometric Mean Concentrations (GMCs) of Anti-Pneumococcal Antibodies After Pneumococcal Conjugated Vaccine (PCV) in Groups 3 and 4		Day 30 after the 12-month vaccination

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Anti-Pneumococcal Concentrations ≥ 0.35 μg/mL After Pneumococcal Conjugate Vaccine (PCV) in Group 3 and Group 4		Day 30 after 12-month vaccination
Percentage of Participants Reporting a Solicited Injection Site and Systemic Reactions After Menactra® Vaccination at 9 Months of Age	Solicited injection site reactions: Injection site tenderness, injection site erythema, and injection site swelling. Solicited systemic reactions: Fever (temperature), vomiting, crying abnormal, drowsiness, appetite lost, and irritability.	Days 0 to 7 after vaccination
Percentage of Participants With Solicited Injection Site and Systemic Reactions After Vaccination at 12 Months of Age		Days 0 to 7 after 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: December 1, 2006
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: January 12, 2007
• First Submitted That Met QC Criteria: January 12, 2007
• First Posted (Estimate): January 15, 2007

Study Record Updates

• Last Update Posted (Estimate): April 14, 2016
• Last Update Submitted That Met QC Criteria: April 12, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Pneumococcal conjugate vaccine; Meningococcal meningitis; Measles; Haemophilus influenzae type b; Mumps; Rubella; Menactra vaccine; Varicella vaccines
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Central Nervous System Infections; DNA Virus Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Morbillivirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; Herpesviridae Infections; Varicella Zoster Virus Infection; Meningitis, Bacterial; Central Nervous System Bacterial Infections; Meningococcal Infections; Neisseriaceae Infections; Togaviridae Infections; Rubivirus Infections; Measles; Herpes Zoster; Meningitis, Meningococcal; Meningitis; Chickenpox; Rubella; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: MTA37