A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of Homologous and Heterologous Prime-Boost Regimens Comprising DNA-HIV-PT123, NYVAC-HIV-PT1 and NYVAC-HIV-PT4, and AIDSVAX B/E in Healthy, HIV-Uninfected US and South African Adults
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV Infections
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Primary Endpoint
- Frequency of severe local and systemic reactogenicity signs and symptoms
- Status
- Withdrawn
- Last Updated
- 4 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety and immune response to two different HIV vaccine regimens in healthy, HIV-uninfected people in the United States and South Africa.
Detailed Description
This study will evaluate the safety, tolerability, and immune response to two different vaccine schedules of a prime with either DNA HIV vaccine (DNA-HIV-PT123), or NYVAC HIV vaccine (NYVAC-HIV-PT1 and NYVAC-HIV-PT4) followed by a boost combination of NYVAC HIV vaccine (PT1 \& PT4) and AIDSVAX B/E. Study researchers will also evaluate whether body mass index (BMI) and/or sex impact the immunogenicity of the vaccine regimens in participants from South Africa, and look at regional differences in immunologic responses between United States and South African participants. The study will enroll 264 healthy, HIV-uninfected people, ages 18-50, in the United States and South Africa. Participants will be randomly assigned to one of three groups and receive either one of the vaccine regimens or placebo. Participants will receive injections according to their assigned group schedule at study entry (Month 0) and Months 1, 3, and 6. 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. Study visits will occur at study entry, and Months 1, 1.5, 3, 3.5, 6, 6.5, 9, and 12. All study visits will include a physical examination, HIV risk reduction counseling, and interviews and/or questionnaires. Select study visits will include urine collection, an electrocardiogram (ECG), blood collection, a pregnancy test for female participants, and HIV testing. At some visits, some participants may also provide samples of cervical fluid, rectal fluid, and/or semen. Study researchers will contact participants by telephone or e-mail once a year for 3 years following the first vaccination for follow-up health monitoring.
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 and greater than or equal to 13.0 g/dL for participants 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, 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 during the planned duration of this study
- •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 101 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 or (South Africa) Medicines Control Council (MCC). For participants who have received control/placebo in an experimental vaccine trial, the HVTN 101 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 101 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
Frequency of severe local and systemic reactogenicity signs and symptoms
Time Frame: Measured within the initial 7-day period following each vaccination visit and followed until resolution
Including pain, tenderness, maximum severity of pain and/or tenderness, erythema, induration, fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and maximum severity of systemic symptoms
Reports of serious adverse events (SAEs) throughout the active surveillance period
Time Frame: Measured through the end of participants' 3-year follow-up period
Measurements of laboratory measures of safety
Time Frame: Measured through participants' last study visit at Month 12
Including boxplots of white blood cells (WBC), neutrophils, lymphocytes, hemoglobin, platelets, alanine aminotransferase (ALT), and creatinine at baseline and following vaccinations, by treatment arm
Magnitude and breadth of HIV-specific binding antibody responses as assessed by multiplex assay
Time Frame: Measured 2 weeks after the second NYVAC+AIDSVAX B/E boost or final placebo injection
HIV-specific CD4+ and CD8+ T-cell response rates
Time Frame: Measured 2 weeks after the second NYVAC+AIDSVAX B/E boost or final placebo injection
Magnitude of HIV-specific CD4+ and CD8+ T-cell responses
Time Frame: Measured 2 weeks after the second NYVAC+AIDSVAX B/E boost or final placebo injection
Humoral and cellular vaccine responses for each vaccine regimen in South African women with low BMI and with high BMI
Time Frame: Measured through participants' last study visit at Month 12
Humoral and cellular responses to DNA prime followed by NYVAC+AIDSVAX B/E in U.S. adults compared to South African adults
Time Frame: Measured through participants' last study visit at Month 12
Humoral and cellular responses to NYVAC prime followed by NYVAC+AIDSVAX B/E boost in U.S. adults compared to South African adults
Time Frame: Measured through participants' last study visit at Month 12
Frequency of adverse events (AEs)
Time Frame: Measured through participants' last study visit at Month 12
Including by treatment arm, by body system, Medical Dictionary for Regulatory Activities (MedDRA) preferred term, severity, and assessed relationship to study products
Humoral and cellular vaccine responses for each vaccine regimen in South African men with low BMI and with high BMI
Time Frame: Measured through participants' last study visit at Month 12
Secondary Outcomes
- Humoral and cellular vaccine responses to DNA prime with NYVAC+AIDSVAX B/E boosts and NYVAC prime with NYVAC+AIDSVAX B/E boosts regimens in South African women compared to South African men(Measured through participants' last study visit at Month 12)
- Magnitude and breadth of HIV-specific binding antibody responses as assessed by multiplex assay(Measured 2 weeks after the second NYVAC+AIDSVAX B/E boost or final placebo injection)
- HIV-specific CD4+ and CD8+ T-cell response rates(Measured 2 weeks after the second NYVAC+AIDSVAX B/E boost or final placebo injection)
- Humoral and cellular responses to DNA prime with NYVAC+AIDSVAX B/E boosts and NYVAC prime with NYVAC+AIDSVAX B/E boosts regimens in South African women(Measured through participants' last study visit at Month 12)
- Humoral and cellular responses to DNA prime with NYVAC+AIDSVAX B/E boosts and NYVAC prime with NYVAC+AIDSVAX B/E boosts in South African men(Measured through participants' last study visit at Month 12)
- Humoral and cellular responses to DNA prime with NYVAC+AIDSVAX B/E boosts and NYVAC prime with NYVAC+AIDSVAX B/E boosts regimens in low BMI South African adults(Measured through participants' last study visit at Month 12)
- Magnitude of HIV-specific CD4+ and CD8+ T-cell responses(Measured 2 weeks after the second NYVAC+AIDSVAX B/E boost or final placebo injection)
- Humoral and cellular vaccine responses to DNA prime with NYVAC+AIDSVAX B/E boosts and NYVAC prime with NYVAC+AIDSVAX B/E boosts regimens in South African adults with low and with high BMI(Measured through participants' last study visit at Month 12)
- Humoral and cellular responses to DNA prime with NYVAC+AIDSVAX B/E boosts and NYVAC prime with NYVAC+AIDSVAX B/E boosts in high BMI South African adults(Measured through participants' last study visit at Month 12)