Study of the HIV gp120/NefTat/AS02A Vaccine to Treat Individuals With Chronic HIV-1 Infection on Highly Active Antiretroviral Therapy (HAART)
This study will test the safety and immunogenicity of the gp120/NefTat/AS02A vaccine candidate in individuals with chronic HIV-1 infection successfully treated with HAART. The rationale for this study is based on previous scientific experiments, including data indicating that this vaccine can elicit strong HIV-1-specific T cell immune responses in humans and monkeys and lead to a retardation of HIV-1 disease progression in animal models of HIV-1 infection.
The HIV vaccine to be administered during this study consists of three recombinant HIV clade B viral antigens: the envelope glycoprotein gp120 and two regulatory proteins, Nef and Tat.The antigens are formulated in a proprietary adjuvant, AS02A, comprised of two immunostimulants in an oil-in-water emulsion (gp120/NefTat/AS02A). The vaccine and the adjuvant are manufactured and provided for the study by GlaxoSmithKline Biologicals, Rixensart, Belgium. The drugs will be given by intramuscular (IM) injection at a standard dose of 20 mg together with 0.5 ml of the AS02A adjuvant.
Twenty HIV-1 infected individuals will be randomly enrolled into three different study groups, receiving either the gp120/NefTat/AS02A vaccine (10 individuals), the AS02A adjuvant alone (5 individuals) or a placebo (5 individuals). After obtaining informed consent, subjects will have a history and physical exam performed and have laboratory tests to confirm they meet all inclusion and exclusion entry criteria. Women of childbearing potential will have a pregnancy test prior to each injection of the investigational product. Injections with vaccine, adjuvant alone, or placebo will then be performed at weeks 0, 4, and 12. Study participants will undergo close monitoring after each vaccination. Blood samples will be obtained for immunological assays at study baseline (2 times) and weeks 2, 4, 6, 12, 14, 24, and 48. All patients will maintain their antiretroviral treatment regimen during the entire study period.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Phase I, Randomized, Double-Blind Clinical Trial of the HIV gp120/NefTat/AS02A Vaccine Candidate in Subjects With Well-Controlled Chronic HIV-1 Infection on Highly Active Antiretroviral Therapy (HAART)|
- Occurrence, intensity and relationship of any local and general signs and symptoms during a 7-day follow-up period (i.e. day of vaccination and 6 subsequent days) after each vaccination [ Designated as safety issue: Yes ]
|Study Start Date:||June 2005|
|Study Completion Date:||January 2010|
|Primary Completion Date:||September 2007 (Final data collection date for primary outcome measure)|
Biological: HIV gp120/NefTat/AS02A Vaccine
DESIGN: This study is a randomized, double blind clinical trial of the gp120/NefTat/AS02A vaccine in individuals with well-controlled chronic HIV-1 infection who have been successfully treated with highly active antiretroviral therapy (HAART). The adjuvanted protein vaccine candidate consists of three recombinant viral antigens: the envelope glycoprotein gp120 and two regulatory proteins, Nef and Tat. The latter are expressed as one recombinant fusion protein, NefTat. The antigens are formulated in the proprietary AS02A adjuvant. The goal of this trial is to assess the safety and immunogenicity of the gp120/NefTat/AS02A vaccine in HIV-1-infected individuals.
DURATION: 48 weeks
SAMPLE SIZE: 20 subjects
POPULATION: Subjects with chronic HIV-1 infection receiving highly active antiretroviral therapy (HAART) with HIV RNA levels <50 copies/mL on at least two measurements in the previous 6 months and a CD4+ T cell count >400 cells/mm3 within 45 days of study entry will be eligible for this study.
REGIMEN: Enrolled patients will be randomized to receive either the vaccine (gp120/NefTat/AS02A) (10 individuals), the AS02A adjuvant only (5 individuals) or a placebo (5 individuals). Injections will be administered IM at weeks 0, 4, and 12.
OBJECTIVES: The two primary objectives of this study are:
- to evaluate the safety and tolerability of the gp120/NefTat/AS02A vaccine in individuals with well-controlled chronic HIV-1 infection on HAART; and
- to evaluate the cell-mediated immune response (IL-2 secreting CD4+ T cells) to at least one vaccinal antigen induced by the vaccine-adjuvant combination in individuals with chronic HIV-1 infection on successful HAART, at two weeks after the third vaccination.
ENDPOINTS: The two co-primary study endpoints will be:
- the occurrence, intensity, and relationship of any local and general signs and symptoms during a 7-day follow-up period after each vaccination (primary safety endpoint); and
- the changes in the frequency of IL-2 secreting CD4+ T cells in response to at least one vaccinal antigen (primary immunogenicity endpoint) in the three different patient categories, assessed two weeks after the third vaccination.
|United States, Massachusetts|
|Massacusetts General Hospital -Infectious Disease Unit|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Marcus Altfeld, MD/PhD||Massachusetts General Hospital|
|Principal Investigator:||Mathias Lichterfeld, MD/PhD||Massachusetts Genral Hosptial|