Safety and Immunogenicity of 13-Valent Pneumococcal Conjugate Vaccine (13vPnC) in HIV-Infected Subjects 6 Years of Age or Older Who Are Naive to Pneumococcal Vaccine

Study Overview
=================
Brief Summary
-----------------
The study will evaluate the safety, tolerability and immunogenicity of a 13-valent pneumococcal conjugate vaccine (13vPnC) in HIV-infected subjects 6 years of age or older who have not been previously immunized with a pneumococcal vaccine. All subjects will receive 3 doses of 13vPnC and 1 dose of 23-valent pneumococcal polysaccharide vaccine (23vPS), with each dose given approximately 1 month apart.

Official Title
-----------------
A Phase 3, Open-label, Single-Arm Trial to Evaluate the Safety, Tolerability and Immunogenicity of 2 and 3 Doses of 13vPnC in HIV-Infected Subjects 6 Years of Age and Older Who Have Not Been Previously Immunized With Pneumococcal Vaccine

Conditions
-----------------
HIV Infections, Pneumococcal Infections

Intervention / Treatment
-----------------
* Biological: 13-valent Pneumococcal Conjugate Vaccine (13vPnC)
* Biological: 23-valent Pneumococcal Polysaccharide Vaccine (23vPS)
* Procedure: Blood draw
* Procedure: Blood draw


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Human immunodeficiency virus (HIV)-infected subjects aged 6 years or older Viral load < 50,000 copies/mL and CD4+ T cell count >= 200/uL within 6 months before study vaccination Receiving stable highly active antiretroviral therapy (HAART) or not currently receiving any antiretroviral therapy No previous vaccination with a pneumococcal vaccine Subject or parent/legal guardian able to complete an electronic diary Exclusion Criteria: Acquired immune deficiency syndrome (AIDS) at time of enrollment Current illicit substance and/or alcohol abuse History of active chronic viral hepatitis Previous anaphylactic reaction to a vaccine or vaccine-related component Serious chronic disorders including metastatic malignancy and end-stage renal disease

Ages Eligible for Study
-----------------
Minimum Age: 6 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>3 doses of 13vPnC and 1 dose of 23vPS, each dose given approximately 1 month apart | Biological: 13-valent Pneumococcal Conjugate Vaccine (13vPnC)<br>* 13vPnC; 3 vaccinations given at approximately 1 month intervals at visits 1-3<br>Biological: 23-valent Pneumococcal Polysaccharide Vaccine (23vPS)<br>* 23vPS; 1 vaccination given at visit 4 (approximately 1 month after visit 3)<br>Procedure: Blood draw<br>* Blood draw; 5 blood draws approximately 1 month apart taken prior to vaccination at visits 1-4 and visit 5 (approximately 1 month after visit 4).<br>Procedure: Blood draw<br>* 1 or 2 blood draws for CD4+ T cell count and HIV viral load at least 6 weeks apart, if subject does not have 2 CD4+ T cell counts and HIV viral load counts within 6 months before visit 1.<br>* Other names: Screening blood draw(s);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Fold Rise (GMFR) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody From 1 Month After 13vPnC Dose 2 to 1 Month After 13vPnC Dose 3 in All Participants | GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from 1 month after 13vPnC Dose 2 to 1 month after 13vPnC Dose 3 were computed using the logarithmically transformed assay results. Confidence interval (CI) for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from both 1 month after 13vPnC Dose 2 and after 13vPnC Dose 3 blood draws. | 1 month after 13vPnC Dose 2, 1 month after 13vPnC Dose 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After 13vPnC Dose 3 Relative to 1 Month After 13vPnC Dose 2 in Pediatric, Adult and All Participants | Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) for pediatric, adult and all participants are presented. GMC (13vPnC) and corresponding 2-sided 95 percent (%) CIs were evaluated. Geometric means were calculated using all participants with available data for both 1 month after 13vPnC Dose 2 and after 13vPnC Dose 3 blood draws. CI for GMC were back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations. | 1 month after 13vPnC Dose 2, 1 month after 13vPnC Dose 3 | 
| Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) 1 Month After 13vPnC Dose 3 Relative to 1 Month After 13vPnC Dose 2 in Pediatric, Adult and All Participants | Serotype-specific OPA GMTs for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in the blood samples of pediatric, adult and all participants using a microcolony OPA (mcOPA) assay. GMT (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data for both 1 month after 13vPnC Dose 2 and after 13vPnC Dose 3 blood draws. CI for GMT were back transformations of a CI based on the Student t distribution for the mean logarithm of the titers. | 1 month after 13vPnC Dose 2, 1 month after 13vPnC Dose 3 | 
| Geometric Mean Fold Rise (GMFR) for Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) From 1 Month After 13vPnC Dose 2 to 1 Month After 13vPnC Dose 3 in Pediatric, Adult and All Participants | GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from 1 month after 13vPnC Dose 2 to 1 month after 13vPnC Dose 3 were computed using the logarithmically transformed assay results. Confidence interval (CI) for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from both 1 month after 13vPnC Dose 2 and after 13vPnC Dose 3 blood draws. | 1 month after 13vPnC Dose 2, 1 month after 13vPnC Dose 3 | 
| Geometric Mean Fold Rise (GMFR) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody From 1 Month After 13vPnC Dose 2 to 1 Month After 13vPnC Dose 3 in Pediatric and Adult Participants | GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from 1 month after 13vPnC Dose 2 to 1 month after 13vPnC Dose 3 were computed using the logarithmically transformed assay results. Confidence interval (CI) for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from both 1 month after 13vPnC Dose 2 and after 13vPnC Dose 3 blood draws. | 1 month after 13vPnC Dose 2, 1 month after 13vPnC Dose 3 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
vaccine, 13-valent pneumococcal conjugate vaccine, 23-valent pneumococcal polysaccharide vaccine, human immunodeficiency virus