A Phase 1b Randomized Double-Blind Clinical Trial to Examine Whether Polytopic Administration of VRC rAd5 Gag-pol/Env A/B/C Vaccine Enhances HIV-Specific Cellular Immune Responses in Humans
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV Infections
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 90
- Locations
- 8
- Primary Endpoint
- Number of recognized epitopes as measured by enzyme-linked immunospot (ELISpot)
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the immune response to the Vaccine Research Center (VRC) rAd5 HIV vaccine when the vaccine components are administered in three different ways, in healthy, HIV-uninfected adults.
Detailed Description
The VRC rAd5 HIV vaccine contains four different components. In this study, researchers will examine how the immune system responds to the vaccine when the four components are administered in three different ways: 1. The vaccine dose containing all four components is given as a single injection in one arm, and placebo injections are given in the other arm and both legs. 2. The vaccine dose containing all four components is divided into fourths, and one-fourth of the full dose is given in each arm and leg. 3. The four vaccine components are separated, and a different component is given in each arm and leg. This study will enroll healthy, HIV-uninfected adults. Participants will be randomly assigned to one of three groups. Group 1 will receive the entire dose of vaccine in their right arm and placebo vaccine in the other arm and both legs. Group 2 will receive all four different components of the vaccine, given separately as a different component per each arm and leg. Group 3 will receive the entire vaccine dose divided into fourths, with one fourth of the full dose given in each arm and leg. At a baseline study visit, participants will undergo a physical examination and a medical and medication history review. Female participants will also take a pregnancy test. Participants will complete questionnaires and receive counseling on HIV risk reduction and pregnancy prevention. All participants will then receive vaccine given as four injections-one each in their right arm, left arm, right thigh, and left thigh (except for Group 1, placebo injections are given in left arm and both legs). After receiving the vaccine, participants will remain in the clinic for at least 30 minutes for observation and monitoring of side effects. For 7 days after the vaccination, participants will record any side effects in a symptom log; for the first 3 days after the vaccination, study staff will call participants to ensure they are completing the symptom log. Follow-up visits will occur at Months 1, 4, and 7. These visits will include the baseline study procedures and a blood collection. Participants will be contacted by study researchers once a year for 5 years for follow-up health monitoring. Blood collected during study visits will be saved for future testing.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willing to be followed for the planned duration of the study
- •Able and willing to provide informed consent
- •Demonstrates understanding of this study and that in a previous trial there was an association of increased acquisition of HIV with receipt of that study vaccine; completes a questionnaire prior to vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
- •Willing to receive HIV test results
- •Willing to discuss HIV infection risks, amenable to HIV risk reduction counseling, and committed to maintaining behavior consistent with low risk of exposure to HIV through the last required study visit
- •Willing to be contacted annually after completion of scheduled clinic visits for a total of 5 years following initial study injection
- •Agrees not to enroll in another study of an investigational research agent prior to completion of last required study visit (excludes annual contacts for safety surveillance)
- •In good general health as shown by medical history, physical exam, and screening laboratory tests
- •Assessed by the clinic staff as being at "low risk" of HIV infection on the basis of sexual behaviors. More information on this criterion can be found in the protocol.
- •Body weight greater than or equal to 110 lb (greater than or equal to 50 kg)
Exclusion Criteria
- •Excessive daily alcohol use, frequent binge drinking, chronic marijuana abuse, or any other use of illicit drugs within the 12 months prior to study entry
- •History of newly acquired syphilis, gonorrhea, nongonococcal urethritis, herpes simplex virus type 2 (HSV2), chlamydia, pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B within the 12 months prior to study entry
- •Untreated or incompletely treated syphilis infection
- •HIV vaccine(s) received in a prior HIV vaccine trial. For potential participants who have received control/placebo in an HIV vaccine trial, the HVTN 085 Protocol Safety Review Team (PSRT) will determine eligibility on a case-by-case basis.
- •Non-HIV experimental vaccine(s) received within the 5 years prior to study entry in a previous vaccine trial. Exceptions may be made for vaccines that have subsequently undergone licensure by the FDA. For potential participants who have received control/placebo in an experimental vaccine trial, the HVTN 085 PSRT will determine eligibility on a case-by-case basis. For potential participants who have received an experimental vaccine(s) more than 5 years ago, eligibility for enrollment will be determined by the PSRT on a case-by-case basis.
- •Immunosuppressive medications received within 168 days before first vaccination. (Not excluded: 1) corticosteroid nasal spray for allergic rhinitis; 2) topical corticosteroids for mild, uncomplicated dermatitis; or 3) oral/parenteral corticosteroids given for nonchronic conditions not expected to recur \[length of therapy 10 days or less with completion at least 30 days prior to study entry\].)
- •Blood products received within 120 days before the first vaccination
- •Immunoglobulin received within 60 days before the first vaccination
- •Live attenuated vaccines other than influenza vaccine received within 30 days before the first vaccination or scheduled within 14 days after injection (e.g., measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever)
- •Influenza vaccine or any vaccines that are not live attenuated vaccines and were received within 14 days prior to the first vaccination (e.g., tetanus, pneumococcal, hepatitis A or B)
Outcomes
Primary Outcomes
Number of recognized epitopes as measured by enzyme-linked immunospot (ELISpot)
Time Frame: Measured at 4 weeks following vaccination
Total magnitude of gene-specific CD4 and CD8 T-cell responses as measured by intracellular cytokine staining (ICS)
Time Frame: Measured at 4 weeks following vaccination
Secondary Outcomes
- Polyfunctional CD4 and CD8 T-cell responses across one and multiple antigenic components of VRC rAd5 HIV vaccine as measured by ICS(Measured at 28 weeks following vaccination)
- Total vaccine-specific CD4 and CD8 T-cell responses as measured by ICS(Measured at 28 weeks following vaccination)
- Antibody binding to HIV epitopes by multiplex binding antibody assay and/or peptide array(Measured at 28 weeks following vaccination)
- T-cell receptor beta chain sequence diversity of epitope-specific CD4 and CD8 T cells(Measured at 28 weeks following vaccination)
- Human leukocyte antigen (HLA) type, epitope-specific T-cell responses as measured by ELISpot, ICS, tetramer, and/or other assays(Measured at 28 weeks following vaccination)
- Local and systemic reactogenicity signs and symptoms, laboratory measures of safety, adverse events (AEs), and serious adverse events (SAEs) reported on an expedited basis to the Division of AIDS (DAIDS)(Measured at 28 weeks following vaccination)