Safety & Immunogenicity of 13vPnC in HIV-Infected Subjects Aged 18 or Older Who Were Previously Immunized With 23vPS

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 18 years of age or older who have been previously immunized with at least one dose of 23-valent pneumococcal polysaccharide vaccine (23vPS). All subjects will receive 3 doses of 13vPnC, with each study vaccine dose given approximately 6 months apart.

Official Title
-----------------
A Phase 3, Open-label, Single-Arm Trial to Evaluate the Safety, Tolerability, and Immunogenicity of 3 Doses of 13vPnC Vaccine in HIV-Infected Subjects 18 Years of Age or Older Who Have Been Previously Immunized With 23vPS Vaccine

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

Intervention / Treatment
-----------------
* Biological: 13-valent pneumococcal conjugate vaccine
* Procedure: Blood draw


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subjects aged 18 years or older at the time of enrollment. All female and male subjects who are biologically capable of having children must agree and commit to the use of a reliable method of birth control from the signing of the informed consent form (ICF) until 3 months after the last dose of investigational product. Documented vaccination with 1 or more doses of 23vPS at least 6 months before study enrollment. CD4+ T-cell count >= 200 cells/µ, obtained on the most recent 2 occasions within 6 months before the first investigational product vaccination. HIV-infected subjects with viral load <50,000 copies/mL, obtained on the most recent 2 occasions within 6 months before the first investigational product vaccination. Subject is receiving a stable dose of HAART for at least 6 weeks prior to the first investigational product vaccination, or not currently receiving antiretroviral therapy. Subject is expected to be available for the entire study period (approximately 18 months) and can be contacted by telephone. Subject must be able to complete an electronic diary (e-diary) and complete all relevant study procedures during study participation. Subject is deemed to be eligible for the study on the basis of medical history, physical examination, and clinical judgment. (Note: Subjects with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease 6 weeks before investigational product vaccination, are eligible.) Exclusion Criteria: Subjects with active AIDS related illness, including opportunistic infections or malignancy. Evidence of current illicit substance and/or alcohol abuse, that in the investigator's opinion, precludes the subject from participating in the study or interferes with the evaluation of the study objectives.. Receipt of any licensed or experimental pneumococcal conjugate vaccine prior to enrollment. Contraindication to vaccination with pneumococcal conjugate vaccine. Previous anaphylactic reaction to any vaccine or vaccine-related component. History of culture-proven invasive disease caused by Streptococcus pneumoniae within the last year. Current anticoagulant therapy or a history of bleeding diathesis or any condition associated with prolonged bleeding time that would contraindicate intramuscular injection. (Note: Use of antiplatelet drugs, such as aspirin and clopidogrel, is permitted.) Pregnant or breastfeeding women, as defined by history or positive human chorionic gonadotropin (hCG) urine test. All women of childbearing potential must have a urine pregnancy test. History of active hepatitis with elevation in pretreatment aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values >5 times the upper limit of normal within the last 6 months. Serious chronic disorder or any other disorder that, in the investigator's opinion, precludes the subject from participating in the study or interferes with the evaluation of the study objectives. (Note: Serious chronic disorders include metastatic malignancy, severe chronic obstructive pulmonary disease requiring supplemental oxygen, end-stage renal disease with or without dialysis, and clinically unstable cardiac disease). Any major illness/condition that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in and completion of, the study, or could preclude the evaluation of the subject's response. History of splenectomy. Receipt of any blood products, including immunoglobulin, within 42 days before investigational product vaccination until the last blood draw for the study (approximately 13 months after the first investigational product vaccination). Evidence of dementia or other severe cognitive impairment. Subject who is, in the opinion of the investigator, unable to receive a vaccination in the deltoid muscle of either arm because of insufficient muscle mass. Participation in another study using investigational product from 28 days before study enrollment until the blood draw at visit 6. Between the blood draw at visit 6 and the 6 month follow-up telephone call (visit 7), use of investigational product must be discussed with the Medical Monitor. (Note: Participation in purely observational studies is acceptable.) Residence in a nursing home, long-term care facility, or other institution or requirement of semi-skilled nursing care. An ambulatory resident of a retirement home or village is eligible for the trial. Subject who is a direct relative (child, grandchild, parent, or grandparent) of study personnel, or who is study personnel. Temporary Delay Criteria: Current febrile illness (oral temperature of =38.0°C [100.4°F]) or other acute illness within 48 hours before study vaccine administration. Currently receiving antibiotic therapy, or has completed a course of antibiotic therapy within 10 days before study vaccine administration. Receipt of novel influenza A (H1N1) vaccine within 14 days before investigational product vaccination (seasonal influenza vaccine can be given at any time at the discretion of the investigator).

Ages Eligible for Study
-----------------
Minimum Age: 18 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> | Biological: 13-valent pneumococcal conjugate vaccine<br>* Three doses of 13vPnC given 6 months apart.<br>* Other names: 13vPnC;Procedure: Blood draw<br>* Six blood draws pre-vaccination and 1 month post-vaccination, doses 1-3.<br>|

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

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