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

NCT ID: NCT03382834

Last Updated: 2024-07-03

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

31 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-26

Study Completion Date

2023-07-27

Brief Summary

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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.

Detailed Description

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The selective estrogen receptor modulator (SERM) tamoxifen may enhance the ability of the histone deacetylase inhibitor (HDACi) vorinostat to reverse HIV-1 latency. This study evaluated the safety of tamoxifen therapy combined with vorinostat and the effectiveness of this combination on latent virus reactivation in HIV-1 infected post-menopausal women with virologic suppression on antiretroviral therapy, when compared to vorinostat alone.

The study was conducted in two steps. During Step 1, the study enrolled women with HIV into two groups. Arm A received tamoxifen daily for 38 days, plus a single dose of vorinostat on Days 35 and 38. Arm B had a 38-day observation period with no tamoxifen, plus a single dose of vorinostat on Days 35 and 38. All participants continued to take ART drugs prescribed by their doctors. ART drugs were not be provided by the study.

Study visits during Step 1 occurred at Days 0, 28, 35, 38, 45, and 65. Study visits could include physical examinations, blood collection, electrocardiograms, and adherence assessments.

During Step 2, all participants were followed for 240 additional weeks for annual long-term safety follow-up. These visits were conducted by phone and collected information from participants on vital status and any new cancer diagnoses.

Step 1 and Step 2 have been completed and this results submission pertains to both.

Conditions

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HIV Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A: Tamoxifen + Vorinostat

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.

Group Type EXPERIMENTAL

Tamoxifen

Intervention Type DRUG

20 mg orally

Vorinostat

Intervention Type DRUG

400 mg orally

Antiretroviral drugs

Intervention Type DRUG

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

Arm B: Vorinostat alone

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.

Group Type ACTIVE_COMPARATOR

Vorinostat

Intervention Type DRUG

400 mg orally

Antiretroviral drugs

Intervention Type DRUG

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

Interventions

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Tamoxifen

20 mg orally

Intervention Type DRUG

Vorinostat

400 mg orally

Intervention Type DRUG

Antiretroviral drugs

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rajesh Gandhi, MD

Role: STUDY_CHAIR

Massachusetts General Hospital (MGH) CRS

Eileen Scully, MD, PhD

Role: STUDY_CHAIR

Johns Hopkins University

Locations

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Alabama CRS

Birmingham, Alabama, United States

Site Status

UCLA CARE Center CRS

Los Angeles, California, United States

Site Status

Ucsf Hiv/Aids Crs

San Francisco, California, United States

Site Status

Harbor-UCLA CRS

Torrance, California, United States

Site Status

University of Colorado Hospital CRS

Aurora, Colorado, United States

Site Status

Whitman-Walker Health CRS

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

Site Status

The Ponce de Leon Center CRS

Atlanta, Georgia, United States

Site Status

Northwestern University CRS

Chicago, Illinois, United States

Site Status

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, United States

Site Status

New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, United States

Site Status

Chapel Hill CRS

Chapel Hill, North Carolina, United States

Site Status

Greensboro CRS

Greensboro, North Carolina, United States

Site Status

Cincinnati Clinical Research Site

Cincinnati, Ohio, United States

Site Status

Penn Therapeutics, CRS

Philadelphia, Pennsylvania, United States

Site Status

Puerto Rico AIDS Clinical Trials Unit CRS

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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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.

Reference Type DERIVED
PMID: 35176755 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables

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

Other Identifiers

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38190

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG A5366

Identifier Type: -

Identifier Source: org_study_id

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