Study to Assess Safety and Activity of Combination Therapy of VRC07-523LS and Vorinostat on HIV-infected Persons

NCT03803605 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 18-1217U01AI117844
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Adult participants (18-64 years old) with HIV-1 Infection on ART with a CD4 T cell count ≥ 350 cells/mm3 and viral suppression for ≥ 24 months will be enrolled on this study. Participants will receive two series of combination therapy consisting of one (1) intravenous (IV) dose of VRC-HIVMAB075-00-AB (VRC07-523LS) followed by 10 oral (PO) doses of Vorinostat (VOR) taken every 72 hours. Each series will last approximately 1 month and the two series will be separated by at least one month. Combination ART is maintained throughout the study. Participants will be on this study for approximately 28 weeks (or about 7 months). The purpose of this study is to:

• Evaluate the safety of two series of a VRC07-523LS infusion followed by multiple oral doses of VOR
• Determine if combining VRC07-523LS and VOR can have an impact on non-active HIV virus.

Conditions

HIV-1 Infection

Keywords

VRC07-523LS; Vorinostat; HIV-1; Suppressed; Latency; Reversal; Novel; Monoclonal; Agent; Antibody; Frequency; T Cell; Infection; ART; Resting

Outcome Measures

Primary Outcomes (1)

• Percent of Participants With a Grade 3 or Higher Treatment-Related Adverse Event (AE)

  The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017 was used to measure safety where Grade 3 is defined as severe and Grade 4 is defined as potentially life-threatening. Treatment-Related AEs assessments are considered related to study product as possible, probable, or definite as defined in the protocol.

  First day of study treatment through end of study, a total of approximately 36 weeks

Study Arms (1)

VRC07-523LS + Vorinostat (VOR)

EXPERIMENTAL

Participants will receive two series of combination therapy consisting of one (1) intravenous (IV) dose of VRC-HIVMAB075-00-AB (VRC07-523LS) followed by 10 oral (PO) doses of Vorinostat (VOR) taken every 72 hours.

Biological: VRC07-523LS; Drug: Vorinostat (VOR)

Interventions

VRC07-523LS BIOLOGICAL

VRC07-523LS 40 mg/kg administered intravenously per series (total of 2 infusions administered)

Also known as: VRC-HIVMAB075-00-AB

VRC07-523LS + Vorinostat (VOR)

Vorinostat (VOR) DRUG

Vorinostat 400 mg administered orally every 72 hours for 10 doses per series (A total of 20 400-mg doses administered)

Also known as: Zolinza

VRC07-523LS + Vorinostat (VOR)

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• ≥ 18 years and \< 65 years of age
• Ability and willingness of participant to give written informed consent. Note: Due to the lack of foreseeable benefit to study participants, mentally incompetent participants will not be enrolled.
• HIV infection documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral assay.
• A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
• Note: Continuous ART prior to screening is defined as not missing more than 9 total days in the 3 months prior to screening.
• Permitted regimens include:
• At least 3 ART agents (not counting ritonavir if less than a 200 mg total daily dose or cobicistat as one of the agents)
• Note: One of the agents must include an integrase inhibitor, NNRTI (Non-Nucleoside Reverse Transcriptase Inhibitors), or a boosted-PI (protease inhibitor).
• Two ART agents in which one of the agents is either a boosted PI or an integrase inhibitor.
• Note: Other fully suppressive antiretroviral combinations will be considered on a case-by-case basis.
• Note: Prior changes in, or elimination of, medications for easier dosing schedule, intolerance, toxicity, improved side effect profile or within a drug class are permitted if an alternative suppressive regimen was maintained but not within 30 days prior to screening.
• Note: Changes in drug formulation or dose are allowed (e.g., tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF), ritonavir to cobicistat, or separate ART agent dosing to fixed-dose combination), but none within 30 days prior to screening.
• Ability and willingness of participant to continue ART throughout the study.
• Able and willing to adhere to protocol therapy, schedule, and is judged adherent to antiretroviral therapy.
• Plasma HIV-1 RNA \<50 copies/mL at 3 time points in the previous 24 months prior to screening and never ≥50 copies/mL on 2 consecutive time points in the last 24 months.

You may not qualify if:

• Known allergy or sensitivity to components of VOR
• Serious adverse reactions to VRC07-523LS formulation components, VRC01 or VRC01LS, including history of anaphylaxis and related symptoms such as hives, respiratory difficulties, angioedema, and/or abdominal pain.
• Women without documentation of an FSH level indicating menopause, hysterectomy or bilateral oophorectomy, bilateral tubal ligation, or non-surgical sterilization.
• Receipt of compounds with histone deacetylase (HDAC) inhibitor-like activity, such as valproic acid within 30 days prior to screening. Potential participants may screen after a 30-day washout period.
• Any investigational research agent within 30 days before study entry.
• Note: Co-enrollment in observational only studies is permitted.
• Note: Co-enrollment in other studies using FDA approved medication that are not otherwise listed as prohibited will be evaluated by the study PI and permitted on a case by case basis.
• Plasma HIV RNA ≥150 copies/mL in the 6 months prior to screening.
• Weight \> 115 kg
• Untreated syphilis infection (defined as a positive rapid plasma reagin (RPR) without clear documentation of treatment).
• Note: In cases of untreated syphilis, participant may rescreen following documentation of adequate treatment of syphilis
• Current treatment for HCV with antiviral therapy or participants who have received HCV treatment within 6 months prior to screening.
• Use of any of the following within 90 days prior to entry: immunosuppressive, immunomodulatory, cytokine, or growth stimulating factors such as systemic corticosteroids, cyclosporine, methotrexate, azathioprine, anti-CD25 antibody, interferon (IFN), interleukin-2 (IL-2).
• Current use of Coumadin, warfarin, or other Coumadin derivative anticoagulants.
• Prior receipt of HIV immunotherapy within 6 months prior to screening.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

University of North Carolina Health Care

Chapel Hill, North Carolina, 27514, United States

Location

Related Publications (2)

• Gay CL, James KS, Tuyishime M, Falcinelli SD, Joseph SB, Moeser MJ, Allard B, Kirchherr JL, Clohosey M, Raines SLM, Montefiori DC, Shen X, Gorelick RJ, Gama L, McDermott AB, Koup RA, Mascola JR, Floris-Moore M, Kuruc JD, Ferrari G, Eron JJ, Archin NM, Margolis DM. Stable Latent HIV Infection and Low-level Viremia Despite Treatment With the Broadly Neutralizing Antibody VRC07-523LS and the Latency Reversal Agent Vorinostat. J Infect Dis. 2022 Mar 2;225(5):856-861. doi: 10.1093/infdis/jiab487.

  PMID: 34562096 DERIVED

• Day S, Mathews A, Blumberg M, Vu T, Rennie S, Tucker JD. Broadening community engagement in clinical research: Designing and assessing a pilot crowdsourcing project to obtain community feedback on an HIV clinical trial. Clin Trials. 2020 Jun;17(3):306-313. doi: 10.1177/1740774520902741. Epub 2020 Feb 3.

  PMID: 32009466 DERIVED

MeSH Terms

Conditions

Infections

Interventions

Vorinostat

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Results Point of Contact

• Title: Cynthia Gay, MD, MPH
• Organization: University of North Carolina at Chapel Hill

cynthia_gay@med.unc.edu

919-966-2537

Study Officials

• Cindy L Gay, MD, MPH

  UNC-Chapel Hill

  PRINCIPAL INVESTIGATOR

• David M Margolis, MD

  UNC-Chapel Hill

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single Arm: All participants will receive combination therapy consisting of VRC07-523LS and Vorinostat.

Study Record Dates

• First Submitted: January 10, 2019
• First Posted: January 14, 2019
• Study Start: February 12, 2019
• Primary Completion: January 28, 2021
• Study Completion: January 28, 2021
• Last Updated: December 2, 2021
• Results First Posted: December 2, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)