A Double-Blind Placebo-Controlled Trial of the Safety and Immunogenicity of a Seven Valent Pneumococcal Conjugate Vaccine in Presumed HIV-Infected Infants

To assess whether HIV-infected infants who receive a heptavalent pneumococcal conjugate vaccine have more local reactions at the site of injection and systemic reactions than placebo subjects. To assess whether this vaccine is more immunogenic than placebo following the third vaccination.

Children with HIV infection are at increased risk for invasive pneumococcal infection, particularly bacteremia. A large proportion of pneumococcal disease is caused by a limited number of serotypes. The maximum number of pneumococcal serotypes that can be included in a new conjugate vaccine is felt to be limited by the amount of carrier protein. A heptavalent pneumococcal conjugate vaccine has been developed that consists of pneumococcal capsular saccharides from serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F bound to a diphtheria toxin mutant carrier protein.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Pneumococcal Infections
• Intervention / Treatment: Biological: Pneumococcal Vaccine, Polyvalent (23-valent); Biological: Pneumococcal Conjugate Vaccine, Heptavalent; Biological: Placebo

Detailed Description

Children with HIV infection are at increased risk for invasive pneumococcal infection, particularly bacteremia. A large proportion of pneumococcal disease is caused by a limited number of serotypes. The maximum number of pneumococcal serotypes that can be included in a new conjugate vaccine is felt to be limited by the amount of carrier protein. A heptavalent pneumococcal conjugate vaccine has been developed that consists of pneumococcal capsular saccharides from serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F bound to a diphtheria toxin mutant carrier protein.

Infants are randomized to receive either heptavalent pneumococcal conjugate vaccine or placebo by intramuscular injection at study months 0, 2, and 4, and then at 15 months of age. Additionally, patients receive PNU-IMUNE 23 ( pneumococcal polyvalent vaccine ) at 24 months of age.

• Study Type: Interventional
• Enrollment: 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico
    • San Juan City Hosp. PR NICHD CRS
  • San Juan, Puerto Rico, 009365067
    • Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
• United States
  • California
    • Los Angeles, California, United States, 90033
      • Usc La Nichd Crs
    • Oakland, California, United States, 946091809
      • Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.
    • San Diego, California, United States, 920930672
      • UCSD Maternal, Child, and Adolescent HIV CRS
    • San Francisco, California, United States, 941430105
      • UCSF Pediatric AIDS CRS
    • San Francisco, California, United States, 94110
      • San Francisco Gen. Hosp.
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Univ. of Florida Jacksonville NICHD CRS
    • Miami, Florida, United States, 33161
      • Univ. of Miami Ped. Perinatal HIV/AIDS CRS
  • Georgia
    • Atlanta, Georgia, United States, 30306
      • Emory Univ. School of Medicine, Dept. of Peds., Div. of Infectious Diseases
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Cook County Hosp.
    • Chicago, Illinois, United States, 606143394
      • Chicago Children's CRS
    • Chicago, Illinois, United States, 606371470
      • Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease
  • Louisiana
    • New Orleans, Louisiana, United States, 701122699
      • Tulane/LSU Maternal/Child CRS
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology
    • Baltimore, Maryland, United States, 212874933
      • Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases
  • Massachusetts
    • Boston, Massachusetts, United States, 021155724
      • HMS - Children's Hosp. Boston, Div. of Infectious Diseases
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan NICHD CRS
  • New Jersey
    • New Brunswick, New Jersey, United States, 089030019
      • UMDNJ - Robert Wood Johnson
    • Newark, New Jersey, United States, 071072198
      • NJ Med. School CRS
  • New York
    • Bronx, New York, United States, 10457
      • Bronx-Lebanon Hosp. IMPAACT CRS
    • Great Neck, New York, United States, 11021
      • North Shore-Long Island Jewish Health System, Dept. of Peds.
    • New York, New York, United States, 10032
      • Columbia IMPAACT CRS
    • New York, New York, United States, 10037
      • Harlem Hosp. Ctr. NY NICHD CRS
    • New York, New York, United States, 10016
      • NYU Med. Ctr., Dept. of Medicine
    • New York, New York, United States, 10032
      • Incarnation Children's Ctr.
    • Rochester, New York, United States
      • Strong Memorial Hospital Rochester NY NICHD CRS
    • Stony Brook, New York, United States, 117948111
      • SUNY Stony Brook NICHD CRS
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Med. Univ., Dept. of Peds.
  • North Carolina
    • Durham, North Carolina, United States, 277103499
      • DUMC Ped. CRS
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 191044318
      • The Children's Hosp. of Philadelphia IMPAACT CRS
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hosp. CRS
  • Washington
    • Seattle, Washington, United States, 981050371
      • UW School of Medicine - CHRMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 6 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

• Antipyretics for rectal temperature >= 100.4 F.
• Antiretroviral therapy.

Patients must have:

• HIV positivity.
• Birth weight at least 1800 g (3.75 lb).
• Consent and compliance of parent or guardian.

NOTE:

• Coenrollment in other therapeutic protocols (except ACTG 218, 230, and 279) is permitted.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Enrollment in HIV vaccine trials.
• Major congenital anomalies that are incapacitating, result in immunologic abnormalities, or require major surgical procedures.
• Congenital immunoglobulin deficiency, SS or SC hemoglobinopathy, or asplenia.
• Hypogammaglobulinemia.

Concurrent Medication:

Excluded:

• Prophylactic antipyretics.

Patients with the following prior conditions are excluded:

Acute moderate to severe intercurrent illness or fever within 72 hours prior to study entry.

Prior Medication:

Excluded:

• Any prior pneumococcal vaccine.
• Measles vaccine within 1 month prior to study vaccination.
• Any other routine vaccine within 1 week prior to study vaccination.
• Any immunosuppressant agent, including prednisone, for more than 6 weeks.

Prior Treatment:

Excluded:

• Blood products within 56 days prior to study vaccination.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Patients receiving intramuscular heptavalent pneumococcal conjugate vaccine	Biological: Pneumococcal Vaccine, Polyvalent (23-valent); Administered as an injection at 24 months of age; Biological: Pneumococcal Conjugate Vaccine, Heptavalent; Administered as an injection at 0, 2, 4, and 15 months of age
Placebo Comparator: 2; Patients receiving placebo vaccine	Biological: Pneumococcal Vaccine, Polyvalent (23-valent); Administered as an injection at 24 months of age; Biological: Placebo; Administered at 0, 2, 4, and 15 months of age

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Comparison of adverse reactions between PCV and placebo patients that occur within 48 hours after each injection	Throughout study
Comparison of seroconversion rates and changes in (IgG) ELISA antibody levels between PCV and placebo patients after the primary series	Throughout study

Secondary Outcome Measures

Outcome Measure	Time Frame
Comparison of booster rates in serum ELISA (IgG) antibody levels just before the 4th vaccination and one month after the 4th vaccination in children receiving PCV and placebo	Prior to 4th vaccination and at 1 month after 4th vaccination
Comparison of serum IgG1 and IgG2 subclass and IgA type specific seroconversion rates and changes in antibody levels in response to the primary immunization series and booster vaccination between PCV and placebo patients	Throughout study
To compare the decline of serum total IgG, IgG1, IgG2, and IgA pneumococcal type specific antibody after the 3rd and after the 4th vaccination in PCV versus placebo patients	At a time after the 3rd vaccination and at a time after the 4th vaccination
Modeling of the rates of seroconversion and changes in serum antibody levels in PCV patients, after the primary series and booster series, to clinical HIV staging and T-lymphocyte parameters, as well as B-lymphocyte parameters	Throughout study

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Lederle-Praxis Biologicals
• Investigators: Study Chair: James King, Jr, M.D., University of Maryland, College Park; Study Chair: Sharon Nachman, M.D., SUNY At Stony Brook

Study record dates

Study Major Dates

• Study Completion (Actual): October 1, 1999

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Actual): October 28, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Vaccines, Synthetic; Pneumococcal Infections; Bacterial Vaccines
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Pneumococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: ACTG 292; 11268 (Registry Identifier: DAIDS ES Registry Number)