Selective Estrogen Receptor Modulators to Enhance the Efficacy of Viral Reactivation With Histone Deacetylase Inhibitors

NCT03382834 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: ACTG A536638190
• Study Type: interventional
• Target: 31
• Locations: 2 countries
• Sites: 15

Brief Summary

This study evaluated the effects of tamoxifen exposure in combination with vorinostat on viral reactivation among HIV-1 infected post-menopausal women with virologic suppression on antiretroviral therapy (ART), when compared to vorinostat alone.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (2)

• Proportion of Participants With New Grade 3 or Greater Adverse Events

  Proportion of participants with new Grade 3 or greater adverse events that are considered definitely, probably, or possibly related to study treatment (as judged by the core protocol team). The DAIDS AE Grading Table (corrected Version 2.1, July 2017) was used.

  Measured from study entry through Day 65

• Change From Baseline in Cell-associated HIV-1 RNA in CD4+ T Cells

  Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value of Cell-associated HIV-1 RNA on Day 38 (5 hours post vorinostat) minus the value at baseline.

  Pre-entry, entry, and Day 38

Secondary Outcomes (2)

• Number of Participants With HIV-1 RNA Levels (Measured by Single Copy Assay) Greater or Equal to the Lower Limit of Quantification

  Pre-entry, entry, Day 28, Day 35, Day 38 (5 hours post vorinostat), Day 45, Day 65

• Change From Baseline in Total HIV-1 DNA Levels in CD4+ T Cells

  Pre-entry, entry, and Day 38

Study Arms (2)

Arm A: Tamoxifen + Vorinostat

EXPERIMENTAL

From Day 0 to Day 38, participants will receive tamoxifen orally once a day. On Days 35 and 38, participants will receive a single dose of vorinostat orally.

Drug: Tamoxifen; Drug: Vorinostat; Drug: Antiretroviral drugs

Arm B: Vorinostat alone

ACTIVE COMPARATOR

Day 0 to Day 38 will be an observation period with no tamoxifen. On Days 35 and 38, participants will receive a single dose of vorinostat orally.

Drug: Vorinostat; Drug: Antiretroviral drugs

Interventions

Tamoxifen DRUG

20 mg orally

Arm A: Tamoxifen + Vorinostat

Vorinostat DRUG

400 mg orally

Arm A: Tamoxifen + Vorinostat; Arm B: Vorinostat alone

Antiretroviral drugs DRUG

Participants will receive antiretroviral drugs provided by their own doctors. Antiretroviral drugs will not be provided by the study.

Arm A: Tamoxifen + Vorinostat; Arm B: Vorinostat alone

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infection
• Postmenopausal at study entry with agreement not to participate in assisted reproductive technology in the future.
• CD4+ cell count greater than 300 cells/uL obtained within 90 days prior to study entry.
• Continuous antiretroviral therapy (ART) for at least 2 years prior to enrollment with no known interruption in therapy for greater than 7 days within 90 days prior to study entry.
• Plasma HIV-1 RNA level of less than 20 copies/mL obtained by Roche HIV-1 viral load assay or less than 40 copies/mL obtained by the Abbott assay, within 90 days prior to study entry.
• Ability and willingness of potential participant to provide written informed consent.

You may not qualify if:

• History of venous thromboembolism.
• History of stroke.
• Known history of hypercoagulable state.
• Tobacco smoking or e-cigarette use within 90 days prior to study entry.
• History of any malignancy requiring systemic chemotherapy or systemic immunotherapy.
• History of endometrial or breast cancer or known genetic testing with BRCA positive results indicating an increased risk for breast and ovarian cancer.
• Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, or investigational therapy within 60 days prior to study entry.
• Any systemic hormonal therapy defined as oral or injectable contraceptives, estrogen and combined estrogen-progesterone replacement therapy in the prior 12 months, or a hormone containing intrauterine device (IUD) within 6 months prior to study entry.
• Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulations.

Sponsors & Collaborators

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

Study Sites (15)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

Ucsf Hiv/Aids Crs

San Francisco, California, 94110, United States

Location

Harbor-UCLA CRS

Torrance, California, 90502, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80045, United States

Location

Whitman-Walker Health CRS

Washington D.C., District of Columbia, 20005, United States

Location

The Ponce de Leon Center CRS

Atlanta, Georgia, 30308-2012, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, 02114, United States

Location

New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, 07103, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27599, United States

Location

Greensboro CRS

Greensboro, North Carolina, 27401, United States

Location

Cincinnati Clinical Research Site

Cincinnati, Ohio, 45219, United States

Location

Penn Therapeutics, CRS

Philadelphia, Pennsylvania, 19104, United States

Location

Puerto Rico AIDS Clinical Trials Unit CRS

San Juan, 00935, Puerto Rico

Location

Related Publications (1)

• Scully EP, Aga E, Tsibris A, Archin N, Starr K, Ma Q, Morse GD, Squires KE, Howell BJ, Wu G, Hosey L, Sieg SF, Ehui L, Giguel F, Coxen K, Dobrowolski C, Gandhi M, Deeks S, Chomont N, Connick E, Godfrey C, Karn J, Kuritzkes DR, Bosch RJ, Gandhi RT. Impact of Tamoxifen on Vorinostat-Induced Human Immunodeficiency Virus Expression in Women on Antiretroviral Therapy: AIDS Clinical Trials Group A5366, The MOXIE Trial. Clin Infect Dis. 2022 Oct 12;75(8):1389-1396. doi: 10.1093/cid/ciac136.

  PMID: 35176755 DERIVED

Related Links

• Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017

MeSH Terms

Conditions

HIV Infections

Interventions

Tamoxifen; Vorinostat

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)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

3016283313

Study Officials

• Rajesh Gandhi, MD

  Massachusetts General Hospital (MGH) CRS

  STUDY CHAIR

• Eileen Scully, MD, PhD

  Johns Hopkins University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2017
• First Posted: December 26, 2017
• Study Start: April 26, 2018
• Primary Completion: December 4, 2018
• Study Completion: July 27, 2023
• Last Updated: July 3, 2024
• Results First Posted: December 18, 2019

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by the NIH.
• Access Criteria: With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group. By what mechanism will data be made available? Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://submit.mis.s-3.net/. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data."

Locations

US (14); PR (1)