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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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HIV Infections, Pneumococcal Infections

Intervention / Treatment
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* Biological: Pneumococcal Vaccine, Polyvalent (23-valent)
* Biological: Pneumococcal Conjugate Vaccine, Heptavalent
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccines, Synthetic, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Pneumococcal Infections, Bacterial Vaccines