Clinical trial NCT00000829: A Double-Blind Placebo-Controlled Trial of the Safety and Immunogenicity of a Seven Valent Pneumococcal Conjugate Vaccine in Presumed HIV-Infected Infants
Official title: A Double-Blind Placebo-Controlled Trial of the Safety and Immunogenicity of a Seven Valent Pneumococcal Conjugate Vaccine in Presumed HIV-Infected Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Pneumococcal Infections
Keywords: Vaccines, Synthetic
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Pneumococcal Infections
Bacterial Vaccines
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Lederle-Praxis Biologicals
First posted: 2001-08-31
Enrollment: 60
Sex: ALL
Minimum age (years): 2
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Comparison of adverse reactions between PCV and placebo patients that occur within 48 hours after each injection
timeFrame: Throughout study
measure: Comparison of seroconversion rates and changes in (IgG) ELISA antibody levels between PCV and placebo patients after the primary series
timeFrame: Throughout study
Secondary outcomes:
measure: 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
timeFrame: Prior to 4th vaccination and at 1 month after 4th vaccination
measure: 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
timeFrame: Throughout study
measure: 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
timeFrame: At a time after the 3rd vaccination and at a time after the 4th vaccination
measure: 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
timeFrame: Throughout study
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Usc La Nichd Crs
state: California
city: Oakland
country: United States
facility: Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.
state: California
city: San Diego
country: United States
facility: UCSD Maternal, Child, and Adolescent HIV CRS
state: California
city: San Francisco
country: United States
facility: San Francisco Gen. Hosp.
state: California
city: San Francisco
country: United States
facility: UCSF Pediatric AIDS CRS
state: California
city: Jacksonville
country: United States
facility: Univ. of Florida Jacksonville NICHD CRS
state: Florida
city: Miami
country: United States
facility: Univ. of Miami Ped. Perinatal HIV/AIDS CRS
state: Florida
city: Atlanta
country: United States
facility: Emory Univ. School of Medicine, Dept. of Peds., Div. of Infectious Diseases
state: Georgia
city: Chicago
country: United States
facility: Cook County Hosp.
state: Illinois
city: Chicago
country: United States
facility: Chicago Children's CRS
state: Illinois
city: Chicago
country: United States
facility: Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease
state: Illinois
city: New Orleans
country: United States
facility: Tulane/LSU Maternal/Child CRS
state: Louisiana
city: Baltimore
country: United States
facility: Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases
state: Maryland
city: Boston
country: United States
facility: HMS - Children's Hosp. Boston, Div. of Infectious Diseases
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hospital of Michigan NICHD CRS
state: Michigan
city: New Brunswick
country: United States
facility: UMDNJ - Robert Wood Johnson
state: New Jersey
city: Newark
country: United States
facility: NJ Med. School CRS
state: New Jersey
city: Bronx
country: United States
facility: Bronx-Lebanon Hosp. IMPAACT CRS
state: New York
city: Great Neck
country: United States
facility: North Shore-Long Island Jewish Health System, Dept. of Peds.
state: New York
city: New York
country: United States
facility: NYU Med. Ctr., Dept. of Medicine
state: New York
city: New York
country: United States
facility: Columbia IMPAACT CRS
state: New York
city: New York
country: United States
facility: Incarnation Children's Ctr.
state: New York
city: New York
country: United States
facility: Harlem Hosp. Ctr. NY NICHD CRS
state: New York
city: Rochester
country: United States
facility: Strong Memorial Hospital Rochester NY NICHD CRS
state: New York
city: Stony Brook
country: United States
facility: SUNY Stony Brook NICHD CRS
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Med. Univ., Dept. of Peds.
state: New York
city: Durham
country: United States
facility: DUMC Ped. CRS
state: North Carolina
city: Philadelphia
country: United States
facility: The Children's Hosp. of Philadelphia IMPAACT CRS
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hosp. CRS
state: Texas
city: Seattle
country: United States
facility: UW School of Medicine - CHRMC
state: Washington
city: San Juan
country: Puerto Rico
facility: Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
city: San Juan
country: Puerto Rico
facility: San Juan City Hosp. PR NICHD CRS
Study officials:
affiliation: University of Maryland, College Park
name: James King, Jr, M.D.
role: STUDY_CHAIR
affiliation: SUNY at Stony Brook
name: Sharon Nachman, M.D.
role: STUDY_CHAIR
References: