A Phase 1 Double Blind Placebo-controlled Clinical Trial to Evaluate the Safety and to Compare the Priming Ability of NYVAC Alone Versus NYVAC + AIDSVAX® B/E, and DNA Alone Versus DNA + AIDSVAX® B/E When Followed by NYVAC + AIDSVAX® B/E Boosts in Healthy, HIV-1-uninfected Adult Participants
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV Infections
- Sponsor
- HIV Vaccine Trials Network
- Enrollment
- 96
- Locations
- 1
- Primary Endpoint
- To evaluate the safety and tolerability of i) NYVAC prime with and without AIDSVAX® B/E plus NYVAC + AIDSVAX® B/E boosts; ii) DNA prime with and without AIDSVAX® B/E plus NYVAC + AIDSVAX® B/E boosts;
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
This study will evaluate the safety of and the body's immune response to experimental HIV vaccine regimens using different vaccine priming combination, and boosting with the vaccines NYVAC and AIDSVAX® B/E.
Detailed Description
Although multiple candidate HIV vaccines are being studied, there is not yet an effective preventive HIV vaccine. This study will test 4 experimental HIV vaccine regimens, each boosting with the NYVAC + AIDSVAX® B/E vaccine combination. Priming will be done with NYVAC or DNA vaccines, alone or in combination with AIDSVAX® B/E. The study will enroll 96 healthy participants, ages 18 - 50 years. Participants will be randomly assigned to 1 of 4 groups. In each group, there will be 20 participants who receive the vaccine regimen and 4 receiving only placebo. Injections will take place at months 0, 1, 3, and 6. All groups will enroll simultaneously. Enrollment will be restricted to a maximum of 2 participants per day, with no more than (1) participant in group 1 or 2 and (1) participant in group 3 or 4 until 20 participants have been enrolled with 5 in each group (4 vaccine recipients and 1 placebo recipient in each group). The HVTN 096 PSRT will review the safety and immune response data for the first 168 hours postvaccination on each of these participants, and will determine whether it is safe to proceed with full enrollment. Total study duration will be 60 months: 18 months of clinic visits followed by annual health contacts to a total of 5 years after initial study injection. At the screening visit, participants will give a medical history and undergo a complete physical exam, cardiac symptom assessment (including ECG), urine collection, blood collection, interview, HIV test, and pregnancy test (for participants who were born female). On Days 0, 28, 84, and 168 participants will receive intramuscular (IM) vaccination (vaccine or placebo) into the right and left deltoids. On vaccination visits, participants will also undergo an abbreviated physical exam, cardiac symptom assessment, Social impact assessment, a pregnancy test (for participants who were born female), risk-reduction counseling, and blood collection. Immediately following vaccination, participants will remain in the clinic for observation for 30 minutes; participants will be given a post-vaccination symptom log and instructed on how to complete it. Follow-up visits will consist of a brief physical exam, blood collection, and interview; some follow-up visits may also consist of a urine collection, HIV test, or ECG. Optional mucosal secretion collection, if the participant agrees, will be done on days 0, 168, and 364. The last clinic visit will be at Day 545; after this visit, participants will be contacted for annual health follow-up consisting of confirming vital status, collecting safety information, and reporting a new HIV diagnosis or a pregnancy. A clinic visit will only be required if HIV confirmatory testing is necessary.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age of 18 to 50 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
- •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
- •Good general health as shown by medical history, physical exam, and screening laboratory tests
- •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
- •Intent to participate in another study of an investigational research agent during the planned duration of the HVTN 096/EV04 study
- •Pregnant or breastfeeding
- •HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 096/EV04 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 FDA. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 096/EV04 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 096/EV04 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)
- •Influenza vaccine or any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B)
- •Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination
- •Immunosuppressive medications received within 168 days before first vaccination. (Not excluded: \[1\] corticosteroid nasal spray; \[2\] inhaled corticosteroids; \[3\] topical corticosteroids for mild, uncomplicated dermatitis; or \[4\] a single course of oral/parenteral corticosteroids at doses \< 2 mg/kg/day and length of therapy \< 11 days with completion at least 30 days prior to enrollment.
Outcomes
Primary Outcomes
To evaluate the safety and tolerability of i) NYVAC prime with and without AIDSVAX® B/E plus NYVAC + AIDSVAX® B/E boosts; ii) DNA prime with and without AIDSVAX® B/E plus NYVAC + AIDSVAX® B/E boosts;
Time Frame: 7 days
Local and systemic reactogenicity signs and symptoms, laboratory measures of safety, and adverse and serious adverse events. Signs and symptoms include pain, tenderness, and redness.
To evaluate and compare the durability of antibody response to different priming regimens when followed by two doses of NYVAC/AIDSVAX® B/E: • NYVAC and NYVAC/AIDSVAX® B/E primes (Group 1 versus 2) • DNA and DNA/AIDSVAX® B/E primes (Group 3 versus 4)
Time Frame: Days 182, 196, 273, 364, 455, 545
HIV-specific antibody response as assessed at multiple timepoints between 2 weeks and 12 months after the last boost
To evaluate and compare the body's immune response to 4 prime-boost regimens, comparing between: • NYVAC and NYVAC/AIDSVAX® B/E primes (Group 1 versus 2) • DNA and DNA/AIDSVAX® B/E primes (Group 3 versus 4)
Time Frame: 182 days
HIV-specific binding antibody response as assessed by laboratory assay 2 weeks after the fourth vaccination
Secondary Outcomes
- To evaluate how long the immune response lasts in all 4 groups(Day 364)
- To evaluate and compare the body's immune response to priming regimens, comparing between: • NYVAC and NYVAC/AIDSVAX® B/E primes (Group 1 versus 2) • DNA and DNA/AIDSVAX® B/E primes (Group 3 versus 4)(Day 42)
- To evaluate the body's immune response to different priming regimens when followed by two doses of NYVAC/AIDSVAX® B/E, comparing between: • Group 1 versus 2 • Group 3 versus 4 • Group 1 versus 3 • Group 2 versus 4(Days 98 and 196)
- To evaluate the immune response to the 4 priming regimens(Day 42)