A Phase 1 Trial to Evaluate the Safety, Tolerability, and Immunogenicity of a Prime-Boost Regimen of HIV-1 Nef/Tat/Vif, Env pDNA Vaccine Delivered Intramuscularly With Electroporation and HIV-1 rVSV envC Vaccine 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)
- Enrollment
- 14
- Locations
- 2
- Primary Endpoint
- Frequency of adverse events (AEs)
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety and tolerability of an HIV-1 nef/tat/vif, env pDNA vaccine delivered with electroporation (EP), followed by a recombinant vesicular stomatitis virus (rVSV) HIV envC vaccine boost, in healthy, HIV-uninfected adults.
Detailed Description
This study will evaluate the safety and tolerability of an HIV-1 nef/tat/vif, env pDNA vaccine delivered with EP, followed by a rVSV HIV envC vaccine boost, in healthy, HIV-uninfected adults. Participants will be randomly assigned to one of two groups. Participants in Group 1 will receive the HIV-1 nef/tat/vif, env pDNA vaccine at Day 0 and Months 1 and 3, followed by the rVSV HIV envC vaccine boost at Months 6 and 9. Participants in Group 2 will receive placebo vaccine at Day 0 and Months 1, 3, 6, and 9. Study visits will occur at Day 0, Week 2, and Months 1, 1.5, 3, 3.25, 3.5, 6, 6.25, 6.5, 9, 9.25, 9.5, 12, and 15. Visits may include physical examinations, urine collection, blood collection, HIV testing, risk reduction counseling, assessments, and questionnaires. Participants will be contacted by study staff for follow-up monitoring annually for 3 years following the initial study injection.
Investigators
Eligibility Criteria
Inclusion Criteria
- •General and Demographic Criteria:
- •Age of 18 to 50 years
- •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: 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 3 years following initial study injection
- •Agrees not to enroll in another study of an investigational research agent prior to completion of last required protocol clinic visit (excludes annual health contacts for safety surveillance)
- •Good general health as shown by medical history, physical exam, and screening laboratory tests
- •HIV-Related Criteria:
- •Willingness to receive HIV test results
Exclusion Criteria
- •Allergy to amide-type local anesthetics (bupivacaine \[Marcaine\], lidocaine \[Xylocaine\], mepivacaine \[Polocaine/Carbocaine\], etidocaine \[Duranest\], prilocaine \[Citanest, EMLA® cream\])
- •Presence of implanted electronic medical device (e.g., pacemaker, implantable cardioverter defibrillator)
- •Presence of surgical or traumatic metal implant in the upper limb and/or upper torso
- •Sinus bradycardia (defined as less than 50 bpm on exam) or a history of cardiac arrhythmia: e.g., supraventricular tachycardia, atrial fibrillation, or frequent ectopy
- •Neurological or neuropsychiatric disorder that may interfere with the assessment of safety: e.g., frequent recurring headaches (i.e., a pattern of greater than 1 headache per month affecting activities of daily living (ADLs)/work, frequent or severe/complicated migraines, cluster headaches), a chronic pain syndrome, dizziness, history of meningitis or encephalitis, cranial/spinal/peripheral neuropathy, limb weakness or paralysis, movement disorder, narcolepsy, stroke with sequelae, moderate/severe major depressive disorder, moderate/severe bipolar disorder
- •Deltoid skin fold measurement by caliper greater than 40 mm
- •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, current smoker, known hyperlipidemia
- •Intent to participate in another study of an investigational research agent or any other study that requires non-HVTN HIV antibody testing during the planned duration of the HVTN 112 study
Outcomes
Primary Outcomes
Frequency of adverse events (AEs)
Time Frame: Measured through Month 15
Categorized by MedDRA body system, MedDRA preferred term, severity and assessed relationship to study products. Detailed description of all AEs meeting Division of AIDS (DAIDS) criteria for expedited reporting.
Frequency of local injection/EP site and systemic reactogenicity signs and symptoms
Time Frame: Measured through Month 15
Magnitude of local injection/EP site pain as measured by a visual analog scale (VAS)
Time Frame: Measured through Month 15
Composite of safety laboratory measures: white blood cells (WBCs), neutrophils, lymphocytes, hemoglobin, alkaline phosphatase, platelets, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and creatine phosphokinase (CPK)
Time Frame: Measured through Month 15
Number of participants with early discontinuation of vaccinations and reasons for discontinuation
Time Frame: Measured through Month 15
Severity of local injection/EP site and systemic reactogenicity signs and symptoms
Time Frame: Measured through Month 15
Secondary Outcomes
- Magnitude and breadth of HIV-specific binding antibody responses as assessed by multiplex assay 2 weeks after each boost(Measured through Month 9.5)
- Neutralizing antibody magnitude and breadth against tier 1 and, if applicable, tier 2 HIV-1 isolates as assessed by area under the magnitude-breadth curves 2 weeks after each boost(Measured through Month 9.5)
- HIV-specific CD8+ T-cell response rates and magnitude 2 weeks after the last priming vaccination and 2 weeks after each boost(Measured through Month 9.5)
- HIV-specific CD4+ T-cell response rates and magnitude 2 weeks after the last priming vaccination and 2 weeks after each boost(Measured through Month 9.5)