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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000829
• Other study ID #: ACTG 292
• Secondary ID: 11268
• Status: Completed
• Phase: Phase 1
• Est. completion date: October 1999

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: October 1999
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Months to 6 Months

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• HIV Infections
• Infections
• Pneumococcal Infections

Intervention

Biological:
• Pneumococcal Vaccine, Polyvalent (23-valent)
Administered as an injection at 24 months of age
• Pneumococcal Conjugate Vaccine, Heptavalent
Administered as an injection at 0, 2, 4, and 15 months of age
• Placebo
Administered at 0, 2, 4, and 15 months of age

Locations

Country	Name	City	State
Puerto Rico	San Juan City Hosp. PR NICHD CRS	San Juan
Puerto Rico	Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS	San Juan
United States	Emory Univ. School of Medicine, Dept. of Peds., Div. of Infectious Diseases	Atlanta	Georgia
United States	Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases	Baltimore	Maryland
United States	Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology	Baltimore	Maryland
United States	HMS - Children's Hosp. Boston, Div. of Infectious Diseases	Boston	Massachusetts
United States	Bronx-Lebanon Hosp. IMPAACT CRS	Bronx	New York
United States	Chicago Children's CRS	Chicago	Illinois
United States	Cook County Hosp.	Chicago	Illinois
United States	Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease	Chicago	Illinois
United States	Children's Hospital of Michigan NICHD CRS	Detroit	Michigan
United States	DUMC Ped. CRS	Durham	North Carolina
United States	North Shore-Long Island Jewish Health System, Dept. of Peds.	Great Neck	New York
United States	Texas Children's Hosp. CRS	Houston	Texas
United States	Univ. of Florida Jacksonville NICHD CRS	Jacksonville	Florida
United States	Usc La Nichd Crs	Los Angeles	California
United States	Univ. of Miami Ped. Perinatal HIV/AIDS CRS	Miami	Florida
United States	UMDNJ - Robert Wood Johnson	New Brunswick	New Jersey
United States	Tulane/LSU Maternal/Child CRS	New Orleans	Louisiana
United States	Columbia IMPAACT CRS	New York	New York
United States	Harlem Hosp. Ctr. NY NICHD CRS	New York	New York
United States	Incarnation Children's Ctr.	New York	New York
United States	NYU Med. Ctr., Dept. of Medicine	New York	New York
United States	NJ Med. School CRS	Newark	New Jersey
United States	Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.	Oakland	California
United States	The Children's Hosp. of Philadelphia IMPAACT CRS	Philadelphia	Pennsylvania
United States	Strong Memorial Hospital Rochester NY NICHD CRS	Rochester	New York
United States	UCSD Maternal, Child, and Adolescent HIV CRS	San Diego	California
United States	San Francisco Gen. Hosp.	San Francisco	California
United States	UCSF Pediatric AIDS CRS	San Francisco	California
United States	UW School of Medicine - CHRMC	Seattle	Washington
United States	SUNY Stony Brook NICHD CRS	Stony Brook	New York
United States	SUNY Upstate Med. Univ., Dept. of Peds.	Syracuse	New York

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Lederle-Praxis Biologicals

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of adverse reactions between PCV and placebo patients that occur within 48 hours after each injection		Throughout study
Primary	Comparison of seroconversion rates and changes in (IgG) ELISA antibody levels between PCV and placebo patients after the primary series		Throughout study
Secondary	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
Secondary	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
Secondary	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
Secondary	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