A Phase 1b Clinical Trial to Evaluate the Safety and Immunogenicity of Different Combinations of DNAHIV-PT123, NYVAC-HIV-PT1 and NYVAC-HIV-PT4, and AIDSVAX® B/E in Healthy, HIV Uninfected Adult Participants
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV Infections
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Primary Endpoint
- Laboratory measures of safety
- Status
- Withdrawn
- Last Updated
- 4 years ago
Overview
Brief Summary
This study will evaluate the safety and immune response to five different combinations of three HIV vaccines in healthy, HIV-uninfected adults.
Detailed Description
This study will evaluate the safety, tolerability, and immune response to five different combinations of three HIV vaccines-a DNA vaccine (DNA-HIV-PT123), a NYVAC vaccine (NYVAC-HIV-PT1 and NYVAC-HIV-PT4 injections), and the AIDSVAX® B/E vaccine-in healthy, HIV-uninfected adult participants. The study will enroll 180 healthy, HIV-uninfected participants aged 18 to 50 years. The participants will be randomly assigned to one of five groups. All participants will receive injections according to their assigned group schedule at study entry (Month 0) and Months 1, 3, and 6. The immune response of different prime and boost vaccine strategies will be tested in Groups 1 through 4, and the immune response of the co-administration of the DNA and AIDSVAX® B/E vaccine will be tested in Group 5. Group 1 participants will receive AIDSVAX® B/E as a prime followed by NYVAC as a boost; Group 2 participants will receive NYVAC as a prime followed by an AIDSVAX® B/E boost; Group 3 participants will receive AIDSVAX® B/E as a prime followed by a DNA boost; Group 4 participants will receive a DNA prime followed by an AIDSVAX® B/E boost; and Group 5 participants will receive both the DNA and AIDSVAX® B/E vaccines at each of the 4 vaccination visits. Total study duration will be approximately 42 months and will involve 12 months of scheduled clinic visits at screening, study entry \[Month 0\], and Months 0.5, 1, 1.5, 3, 3.5, 6, 6.5, 9, and 12) followed by annual health contacts via e-mail or phone to a total of 3 years following initial study injection. All study visits will include a physical exam, HIV risk reduction counseling, and an interview and/or questionnaire. Select study visits will include blood collection, urine collection, an electrocardiogram (ECG), and a pregnancy test for participants who were born female. For participants in Groups 1 and 2, select study visits will also include an assessment of cardiac symptoms. Participants will remain in the clinic for 30 minutes after receiving the vaccines for observation and monitoring. For 7 days after receiving the vaccines, participants will record their symptoms and report them to study researchers.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willingness to be followed for the planned duration of the study
- •Ability and willingness to provide informed consent
- •Assessment of understanding: participant 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 3 years following initial study injection
- •Agrees not to enroll in another study of an investigational research agent before the last required protocol clinic visit
- •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
- •Hemoglobin greater than or equal to 11.0 g/dL for participants who were born female, greater than or equal to 13.0 g/dL for volunteers who were born male
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) greater than or equal to 40; or BMI greater than or equal to 35 with 2 or more of the following: age greater than 45 years, systolic blood pressure greater than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg, or known hyperlipidemia
- •Intent to participate in another study of an investigational research agent before the last required protocol clinic visit
- •Pregnant or breastfeeding
- •HIV vaccine(s) received in a prior HIV vaccine trial. For participants who have received control/placebo in an HIV vaccine trial, the HVTN 102 Protocol Safety Review Team (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 participants who have received control/placebo in an experimental vaccine trial, the HVTN 102 PSRT will determine eligibility on a case-by-case basis. For participants who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the HVTN 102 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 (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 first vaccination (e.g., 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
Outcomes
Primary Outcomes
Laboratory measures of safety
Time Frame: Measured through participants' last study visit at Month 12
Adverse events (AEs) and serious adverse events (SAEs)
Time Frame: Measured through last annual health contact at Month 36
HIV-specific binding antibody (Ab) response as assessed by binding Ab multiplex assay
Time Frame: Measured 2 weeks after the 4th vaccination (Month 6)
Local and systemic reactogenicity signs and symptoms
Time Frame: Measured up to 7 days post the last vaccination
Response rate and magnitude of CD4 and CD8 T-cell responses as assessed by intracellular cytokine staining (ICS) assays
Time Frame: Measured 2 weeks after the 4th vaccination (Month 6)
Secondary Outcomes
- HIV-specific binding Ab and T-cell responses(Measured 2 weeks after the 4th vaccination (Month 6))
- HIV-specific Ab and T-cell responses(Measured 6 months after the 4th vaccination (Month 12))
- Neutralizing antibody (nAb) magnitude and breadth against tier 1 and tier 2 HIV-1 isolates as assessed by area under the magnitude-breadth curves(Measured 2 weeks after the 4th vaccination (Month 6))