Live Zoster Vaccine in HIV-Infected Adults on Antiretroviral Therapy
|Herpes Zoster HIV Infections||Biological: ZOSTAVAX Biological: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
|Official Title:||A Phase II, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety, Tolerability, and Immunogenicity of ZOSTAVAX® (Zoster Vaccine Live) in Human Immunodeficiency Virus (HIV)-1-Infected Adults on Potent Combination ART With Conserved Immune Function|
- Number of Participants With Composite Safety Endpoint of the Occurrence of Serious Adverse Events (SAEs) or Division of AIDS (DAIDS) Grade 3 and 4 Signs and Symptoms, Excluding SAEs Related to Trauma [ Time Frame: During the 6 week study period after receipt of any dose of ZOSTAVAX ]Although the study was designed as a randomized trial, it was not powered to detect safety related differences between treatment arms. The safety of ZOSTAVAX was determined by comparing the number of subjects from the active arm who experienced safety endpoint to the number from a pre-specified decision rule, which was calculated based on a similar population and calibrated using the number of safety endpoints observed from the placebo arm. The pre-specified decision rule is that ZOSTAVAX would be considered to have acceptable safety if no more than 18 subjects experience a study-defined composite safety endpoint.
- VZV Antibodies as Measured by gpELISA [ Time Frame: Within 6 weeks following one or two doses of ZOSTAVAX ]VZV antibody titer measured by gpELISA after one or two doses of ZOSTAVAX/placebo
- VZV-specific Cellular Immune Responses by Intracellular Cytokine Staining and/or ELISPOT Assays in the First 40 Subjects Entering in Each CD4 Stratum at the Opening of Stage II [ Time Frame: Within 6 weeks following one or two doses of ZOSTAVAX ]
|Study Start Date:||April 2009|
|Study Completion Date:||December 2011|
|Primary Completion Date:||September 2011 (Final data collection date for primary outcome measure)|
Participants with CD4 cell counts of 200 cells/uL or greater in Stages 1 and 2, stratified by CD4 cell counts (200-349 cells/uL vs. >=350 cells/uL), will be given one dose of ZOSTAVAX (Zoster Vaccine Live) at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination after which a safety assessment will be conducted.
Subcutaneous injection of 0.65 mL of ZOSTAVAX at Day 0 and Week 6
Placebo Comparator: 2
Participants with CD4 cell counts of 200 cells/uL or greater in Stages 1 and 2, stratified by CD4 cell counts (200-349 cells/uL vs. >=350 cells/uL), will be given one dose of placebo at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination after which a safety assessment will be conducted
Subcutaneous injection of 0.65 mL of placebo at Day 0 and Week 6
The varicella-zoster virus (VZV) which causes herpes zoster (HZ), or shingles, is associated with a painful skin rash and post-herpetic neuralgia (PHN). The incidence and severity of HZ and PHN increase as immune function decreases, as in elderly or HIV-infected people. The live VZV vaccine, ZOSTAVAX, has been shown to reduce the incidence and severity of HZ and PHN in people over the age of 60. The main purpose of this study is to determine whether a two-dose regimen of ZOSTAVAX is safe and well-tolerated in HIV-infected individuals with conserved immune function.
This study has two stages and two arms. It may last up to 24 weeks per subject. In Stage 1, 48 participants with CD4 cell counts of 200 or more cells/uL will be enrolled (24 participants with a CD4 count between 200 and 349 cells/uL and 24 participants with a CD4 count equaling 350 or more cells/uL). These participants will be randomized 3:1 to receive two doses of ZOSTAVAX or placebo at least six weeks apart. If certain safety criteria are met for Stage 1, enrollment will be opened to Stage 2. Stage 2 will enroll approximately 352 subjects with CD4+ T cell counts >= 200 cells/uL. In Stage 2, participants will be stratified using the same parameters as Stage 1 and will then be randomized 3:1 to receive either two doses of vaccine or placebo according to the same schedule. Participants will be followed for at least 42 days after each vaccination. Temperatures will be collected daily for 42 days following each vaccination. Telephone contact will also be made 2 to 3 days after each vaccination and at 24 weeks following the initial vaccination to obtain information regarding vaccination-related symptoms.
All participants will have between 6 and 8 study visits. At the screening visit, documentation of HIV status is required, and blood and urine collection, a physical exam, medical history, and clinical assessment will occur. At each visit, a targeted physical exam will occur. At some visits, blood and urine collection, and a clinical assessment will occur. Antiretroviral medications are not provided by this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00851786
Show 43 Study Locations
|Study Chair:||Constance A. Benson, MD||University of California, San Diego|
|Study Chair:||Jeffrey L. Lennox, MD||Emory University|