A Phase 1 Randomized, Double-blind, Placebo Controlled Clinical Trial to Evaluate the Safety and Immunogenicity of an HIV-1 Vaccine Regimen of DNA Prime and NYVAC Boost With 3 Different HIV-1 Envelope Inserts (Nat-B Env, CON-S Env, and Mosaic Env) in Healthy, HIV-1-uninfected Adults
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV Infections
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Primary Endpoint
- Frequency and severity of local injection site reactogenicity signs and symptoms
- Status
- Withdrawn
- Last Updated
- 4 years ago
Overview
Brief Summary
The purpose of this study is to test the safety and immune response to three different sets of HIV vaccines in healthy, HIV-uninfected adults.
Detailed Description
The purpose of this study is to evaluate the safety, tolerability, and immune response to three different HIV-1 prime-boost vaccine regimens in healthy, HIV-1-uninfected adults. The regimens will differ by the type of HIV-1 envelope insert (Nat-B env, CON-S env, or Mosaic env) contained in both the DNA prime vaccine and the NYVAC boost vaccine. The study will enroll 180 healthy, HIV-1-uninfected adults in two stages (Part A and Part B). After Part A of the study is fully enrolled, study researchers will evaluate study immunogenicity data to determine whether to enroll participants into Part B. The study design and vaccination schedule for both parts of the study will be the same. Participants will be randomly assigned to one of three groups and receive either one of the experimental vaccine regimens or a placebo vaccine regimen. Participants will receive four total injections: on Day 0 and Day 28 (DNA vaccine or placebo) and on Day 84 and Day 168 (NYVAC vaccine or placebo). Group 1 participants will receive DNA Nat-B env and NYVAC Nat-B env vaccines, Group 2 participants will receive DNA CON-S env and NYVAC CON-S env vaccines, and Group 3 participants will receive DNA Mosaic env and NYVAC Mosaic env vaccines. Total study duration will be either 3 years after enrollment (for participants in the United States) or 5 years after enrollment (for participants in Switzerland). For all participants, study visits will occur on Days 0, 14, 28, 42, 84, 98, 168, 175, 182, 273, 357, and 364. After the last study visit, participants will be contacted annually by phone or e-mail for a total of 3 (U.S. participants) or 5 (Switzerland participants) years to answer questions about their health. At screening, participants will give a medical history; undergo a complete physical exam, blood collection, urine collection, and an electrocardiogram (ECG); and receive risk reduction counseling. At most follow-up visits, participants will undergo an abbreviated physical exam, blood collection, urine collection, and receive risk reduction counseling. Participants will have additional ECGs on Days 98 and 182. At all visits, female participants who were born female will be assessed for pregnancy prevention, and at select visits, will undergo a pregnancy test.
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 for U.S. participants (5 years for participants in Switzerland) 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
- •Hemoglobin greater than or equal to 12.5 g/dL for participants who were born female, or greater than or equal to 13.5 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; less than or equal to 18; or 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, current smoker, 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 099 Protocol Safety Review Team (PSRT) will determine eligibility on a case-by-case basis and the identity of the study control/placebo must be obtained.
- •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 099 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 099 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 and severity of local injection site reactogenicity signs and symptoms
Time Frame: Measured for 3 days following each vaccination visit (Days 0, 28, 84, and 168)
Local injection site signs and symptoms may include pain, tenderness, erythema, induration, and maximum severity of pain and/or tenderness.
Breadth of the T-cell response determined as the number of reactive CD4 and CD8 T-cell epitopes using global potential T-cell epitope (PTEg) peptides
Time Frame: Measured through Day 182 visit
Total magnitude of CD4 and CD8 T-cell responses measured by intracellular cytokine staining (ICS) to PTEg peptide pools
Time Frame: Measured through Day 182 visit
Frequency of adverse events (AEs) categorized by the MedDRA body system, MedDRA preferred term, severity and assessed relationship to study products; detailed description of all AEs meeting DAIDS criteria for expedited reporting (EAE)
Time Frame: Measured through Day 364 visit
MedDRA is the Medical Dictionary for Regulatory Activities.
Laboratory measures of safety
Time Frame: Measured through Day 357 visit
Laboratory measures of safety include white blood cells (WBC), neutrophils, lymphocytes, hemoglobin, platelets, alanine aminotransferase (ALT), alkaline phosphatase (ALK Phos), aspartate aminotransferase (AST), and creatinine.
Frequency and severity of systemic reactogenicity signs and symptoms
Time Frame: Measured for 3 days following each vaccination visit (Days 0, 28, 84, and 168)
Systemic reactogenicity signs and symptoms may include fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and maximum severity of systemic symptoms.
Number of participants with early discontinuation of vaccinations and reason for discontinuation
Time Frame: Measured through Day 364 visit
Secondary Outcomes
- Depth of the T-cell responses, determined as the variant recognition per epitope targeted by responding T cells using PTEg and CHAVI peptides(Measured through Day 182 visit)
- Total magnitude of CD4 and CD8 T-cell responses measured by ICS to PTEg(Measured through Day 182 visit)
- Response rate of CD4 and CD8 T-cell responses to PTEg and CHAVI peptide sets measured by ICS(Measured through Day 182 visit)
- Breadth of the T-cell response determined as the number of reactive CD4 and CD8 T-cell epitopes to PTEg and Center for HIV/AIDS Vaccine Immunology (CHAVI) peptide set(Measured through Day 182 visit)
- Magnitude and breadth of serum neutralizing antibodies (nAbs) to a panel of standardized HIV-1 isolates(Measured through Day 364 visit)
- Magnitude and breadth of HIV-specific binding IgG and IgA Env antibody (Ab) responses as determined by binding Ab multiplex assay (BAMA) and peptide array(Measured through Day 182 visit)