Phase 1b Randomized Double Blind Placebo Controlled Clinical Trial to Evaluate the Safety and Immunogenicity of the Vaccine Regimen ALVAC-HIV (vCP1521) Followed by AIDSVAX® B/E in Healthy, HIV-1 Uninfected Adult Participants in South Africa
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV Infection
- Sponsor
- HIV Vaccine Trials Network
- Enrollment
- 202
- Locations
- 3
- Primary Endpoint
- Magnitude and frequency of HIV-specific CD4+ and CD8+ T-cell responses as assessed by flow cytometry at 2 weeks following the final vaccination of ALVACHIV + AIDSVAX B/E.
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The HIV Vaccine Trials Network (HVTN) is doing a study to test 2 experimental HIV vaccines in combination with 2 licensed vaccines for tetanus and hepatitis B. HIV is the virus that causes AIDS. Tetanus is an infection that causes muscular spasms. Hepatitis B is a virus that can cause liver failure.
About 100 people will take part in this study at multiple sites. The US National Institutes of Health (NIH) is paying for the study.
We are doing this study to answer several questions.
- Are the HIV study vaccines safe to give to people?
- Are people able to take the HIV study vaccines without becoming too uncomfortable?
- How do people's immune systems respond to the HIV study vaccines? (Your immune system protects you from disease.)
- Can people's immune responses to a tetanus or hepatitis B vaccines help us understand how their immune systems might respond to the HIV study vaccines?
- Is there a common immune response to licensed vaccines like the tetanus and hepatitis B vaccines?
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age of 18 to 40 years
- •Access to a participating HVTN CRS and willingness to be followed for the planned duration of the study
- •Ability and willingness to provide informed consent
- •Assessment of understanding: volunteer demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
- •Agrees not to enroll in another study of an investigational research agent
- •Good general health as shown by medical history, physical exam, and screening laboratory tests
- •Willingness to receive tetanus and Hepatitis B vaccination
- •Willingness to receive HIV test results
- •Willingness to discuss HIV infection risks, amenable to HIV risk reduction counseling, and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit
- •Assessed by the clinic staff as being at "low risk" for HIV infection
Exclusion Criteria
- •Blood products received within 120 days before first vaccination
- •Investigational research agents received within 30 days before first vaccination
- •Body mass index (BMI) ≥ 40; or BMI ≥ 35 with 2 or more of the following: age \> 45, systolic blood pressure \> 140 mm Hg, diastolic blood pressure \> 90 mm Hg, current smoker, known hyperlipidemia
- •Intent to participate in another study of an investigational research agent during the planned duration of the HVTN 097 study
- •Pregnant, breastfeeding or lactating
- •History of Hepatitis B viral infection
- •History of tetanus disease Vaccines and other Injections
- •HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 097 PSRT will determine eligibility on a case-by-case basis.
- •Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial. Exceptions may be made for vaccines that have subsequently undergone licensure by the South Africa Medicines Control Council (MCC). For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 097 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the HVTN 097 PSRT on a case-by-case basis.
- •Live attenuated vaccines other than influenza vaccine received within 30 days before first vaccination or scheduled within 14 days after injection (eg, measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever)
Outcomes
Primary Outcomes
Magnitude and frequency of HIV-specific CD4+ and CD8+ T-cell responses as assessed by flow cytometry at 2 weeks following the final vaccination of ALVACHIV + AIDSVAX B/E.
Time Frame: 2 weeks post final vaccination of ALVACHIV + AIDSVAX B/E
HIV-specific total IgG and IgA binding antibody responses as assessed by multiplex assay
Time Frame: 2 weeks following the final vaccination of ALVAC-HIV + AIDSVAX B/E.
Neutralizing antibody magnitude and breadth against tier 1 and tier 2 HIV-1 isolates as assessed by area under the magnitude-breadth curves
Time Frame: 2 weeks following the final vaccination of ALVAC-HIV + AIDSVAX B/E.
Frequency of AEs leading to early participant withdrawal or early discontinuation of study products administration throughout the study.
Time Frame: 19.5 months
Occurrence and level of vaccine-induced IgG binding Ab to gp120 and V1V2 scaffold
Time Frame: 2 week sand 6 months post first-boost
Frequency of local and systemic reactogenicity signs and symptoms, laboratory measures of safety, and a line listing of all AEs meeting DAIDS criteria for expedited reporting.
Time Frame: 13.5 months
Frequency of AEs by body system, Medical Dictionary for Regulatory Activities (MedDRA) preferred term, severity, and assessed relationship to study products
Time Frame: 30 days after each vaccine dose
Frequency of SAEs, adverse events of special interest (AESIs; Appendix K), and new chronic conditions (requiring medical intervention for ≥ 30 days) throughout the study
Time Frame: 19.5 months
Frequency of severe local and systemic reactogenicity signs and symptoms (pain, tenderness, erythema, induration, fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia)
Time Frame: 3 days after each vaccine dose
Composite of safety laboratory measures: white blood cells, neutrophils, lymphocytes, hemoglobin, platelets, alanine aminotransferase, aspartate aminotransferase, alkaline phosphate, and creatinine at baseline and following vaccinations
Time Frame: 19.5 months
Secondary Outcomes
- Anti-V1/V2 IgG binding antibody responses as assessed by multiplex assay(2 weeks following the final vaccination of ALVAC-HIV + AIDSVAX B/E)
- HIV-capturing non-neutralizing antibodies as assessed by competitive virus capture assay(2 weeks following the final vaccination of ALVAC-HIV + AIDSVAX B/E.)
- HIV-specific IgG subclass (IgG1-IgG4) characterization as determined by HIV-1 multiplex Ab assay(2 weeks following the final vaccination of ALVAC-HIV + AIDSVAX B/E.)
- Avidity indices for Env-specific antibodies(2 weeks following the final vaccination of ALVAC-HIV + AIDSVAX B/E.)
- Changes in PBMC gene expression relative to prevaccine levels of key genes expected to change.(19.5 months)
- Cell phenotype assessed by flow cytometric analysis of PBMC subsets.(19.5 months)
- Occurrence and level of vaccine-induced IgG binding Ab to gp120 and V1V2 scaffold(2 weeks and 6 months post second-boost as assessed by multiplex assay)
- Functional humoral immune responses including ADCC and HIV virus capture(19.5 months)
- B-cell ELISpot to quantify Env-specific antibody-producing B cells(2 weeks following the final vaccination of ALVAC-HIV + AIDSVAX B/E.)
- Expression of cytokines (eg, IL-10, IL-13) by multiplex bead array following antigen-specific stimulation of peripheral blood mononuclear cells (PBMC)(2 weeks following the final vaccination of ALVAC-HIV + AIDSVAX B/E.)
- Occurrence, magnitude, character and breadth of systemic HIV-specific binding antibody responses as assessed by multiplex assay(baseline (Time 0 prior to first boost), at 2 weeks and at 6 months following each boost, and at 12 months following the first boost including subtype, subclass and IgG binding Ab to V3 epitopes)
- Titers of antibody-dependent cellular cytotoxicity (ADCC) or antibody-dependent cellular viral inhibition (ADCVI)-mediating antibodies(2 weeks following the final vaccination of ALVAC-HIV + AIDSVAX B/E.)
- HIV-specific humoral and cellular responses 2 weeks following the final vaccination of ALVAC-HIV + AIDSVAX B/E.(2 weeks following the final vaccination of ALVAC-HIV + AIDSVAX B/E.)
- Concentrations of cytokines and chemokines in serum and/or plasma samples.(19.5 months)
- HIV-specific humoral and cellular responses 6 months following the final vaccination of ALVAC-HIV + AIDSVAX B/E.(6 months following the final vaccination of ALVAC-HIV + AIDSVAX B/E.)
- HIV-specific systemic CD4+ and CD8+ T-cell responses(baseline (Time 0 prior to first boost), at 2 weeks and at 6 months following each boost, and at 12 months following the first boost)
- Additional immunogenicity assays may be performed on blood and mucosal samples, including on samples from other timepoints, based on the HVTN Laboratory Assay Algorithm.(19.5 months)
- Systemic neutralizing antibody magnitude and breadth against tier 1 and, if applicable, tier 2 HIV-1 isolates as assessed by area under the magnitude-breadth curves(2 weeks following each boost)