Evaluating 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 Adults

NCT02654080 | Completed Phase 1 DMC

• 2 other identifiers: HVTN 11211988
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

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.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (6)

• Frequency of local injection/EP site and systemic reactogenicity signs and symptoms

  Measured through Month 15

• Severity of local injection/EP site and systemic reactogenicity signs and symptoms

  Measured through Month 15

• Frequency of adverse events (AEs)

  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.

  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)

  Measured through Month 15

• Magnitude of local injection/EP site pain as measured by a visual analog scale (VAS)

  Measured through Month 15

• Number of participants with early discontinuation of vaccinations and reasons for discontinuation

  Measured through Month 15

Secondary Outcomes (4)

• 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

• 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

• 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

Study Arms (2)

Group 1: Vaccine

EXPERIMENTAL

Participants will receive the HIV-1 nef/tat/vif, env pDNA vaccine at Day 0 and Months 1 and 3. They will receive the rVSV HIV envC vaccine boost at Months 6 and 9.

Biological: HIV-1 nef/tat/vif, env pDNA vaccine; Biological: rVSV HIV envC vaccine

Group 2: Placebo

PLACEBO COMPARATOR

Participants will receive placebo vaccine at Day 0 and Months 1, 3, 6, and 9.

Biological: Placebo

Interventions

HIV-1 nef/tat/vif, env pDNA vaccine BIOLOGICAL

1500 mcg to be administered as 0.5 mL intramuscular (IM) in the deltoid of the non-dominant arm (unless medically contraindicated) using the Ichor Medical Systems TDS EP device

Also known as: ProfectusVax DNA Plasmid HIV-1 nef/tat/vif, env

Group 1: Vaccine

rVSV HIV envC vaccine BIOLOGICAL

1 × 10\^7 PFU to be administered as 1 mL IM in the deltoid of the non-dominant arm (unless medically contraindicated)

Also known as: ProfectusVaxVSV IN HIV envC

Group 1: Vaccine

Placebo BIOLOGICAL

Sodium Chloride for Injection, USP 0.9%; At Months 0, 1, and 3: administered as 0.5 mL IM in the deltoid of the non-dominant arm (unless medically contraindicated) using the Ichor Medical Systems TDS EP device. At Months 6 and 9: administered as 1 mL IM in the deltoid of the non-dominant arm (unless medically contraindicated).

Group 2: Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling
• Assessed by the clinic staff as being at "low risk" for HIV infection and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit
• Hemogram/Complete Blood Count (CBC):
• Hemoglobin greater than or equal to 11.0 g/dL for volunteers who were born female, greater than or equal to 13.0 g/dL for volunteers who were born male
• White blood cell count equal to 3,300 to 12,000 cells/mm\^3

You may not qualify if:

• General:
• 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
• Pregnant or breastfeeding
• Active duty and reserve U.S. military personnel
• Vaccines and Other Injections:
• HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 112 PSRT will determine eligibility on a case-by-case basis.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

Case Clinical Research Site

Cleveland, Ohio, 44106, United States

Location

Penn Prevention CRS

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Wilson GJ, Rodriguez B, Li SS, Allen M, Frank I, Rudnicki E, Trahey M, Kalams S, Hannaman D, Clarke DK, Xu R, Egan M, Eldridge J, Pensiero M, Latham T, Ferrari G, Montefiori DC, Tomaras GD, De Rosa SC, Jacobson JM, Miner MD, Elizaga M; HIV Vaccine Trials Network 112 Protocol Team. Cellular and humoral responses to an HIV DNA prime by electroporation boosted with recombinant vesicular stomatitis virus expressing HIV subtype C Env in a randomized controlled clinical trial. Vaccine. 2023 Apr 17;41(16):2696-2706. doi: 10.1016/j.vaccine.2023.03.015. Epub 2023 Mar 17.

  PMID: 36935288 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Genes, env

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Genes, Viral; Genes, Microbial; Genes; Genome Components; Genome; Genetic Structures; Genetic Phenomena; Genome, Microbial; Genome, Viral

Study Officials

• Greg Wilson

  Vanderbilt University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2016
• First Posted: January 13, 2016
• Study Start: March 1, 2016
• Primary Completion: August 24, 2017
• Study Completion: July 1, 2019
• Last Updated: October 15, 2021

Record last verified: 2021-10

Locations

US (2)