Clinical Trials

MainTitle

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

This study is ongoing, but not recruiting participants.
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)


Information provided by (Responsible Party)
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier
NCT03382834

First received: December 19, 2017
Last updated: December 17, 2019
Last Verified: December 2019
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV Infections

Drug : Tamoxifen
Drug : Vorinostat
Drug : Antiretroviral drugs
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Selective Estrogen Receptor Modulators to Enhance the Efficacy of Viral Reactivation With Histone Deacetylase Inhibitors

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures

  • Proportion of Participants With New Grade 3 or Greater Adverse Events [ Time Frame: Measured from study entry through Day 65 ]
    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.
  • Change From Baseline in Cell-associated HIV-1 RNA in CD4+ T Cells [ Time Frame: Pre-entry, entry, and Day 38 ]
    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.
Secondary Outcome Measures:
  • Number of Participants With HIV-1 RNA Levels (Measured by Single Copy Assay) Greater or Equal to the Lower Limit of Quantification [ Time Frame: Pre-entry, entry, Day 28, Day 35, Day 38 (5 hours post vorinostat), Day 45, Day 65 ]
    Number of participants with HIV-1 RNA levels measured by single copy assay (SCA) greater or equal to the lower limit of quantification (LOQ). The lower limit of quantification for this study was 0.47 copies/mL.
  • Change From Baseline in Total HIV-1 DNA Levels in CD4+ T Cells [ Time Frame: Pre-entry, entry, and Day 38 ]
    Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value of Total HIV-1 DNA on Day 38 (5 hours post vorinostat) minus the value at baseline.

Enrollment: 31
Study Start Date: April 26, 2018
Estimated Study Completion Date: June 30, 2023
Estimated Primary Completion Date: December 4, 2018 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: 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.
Drug: Tamoxifen

20 mg orally

Drug: Vorinostat

400 mg orally

Drug: Antiretroviral drugs

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

Active Comparator: 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.
Drug: Vorinostat

400 mg orally

Drug: Antiretroviral drugs

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

Detailed Description:

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 will be 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 will be followed for 240 additional weeks for annual long-term safety follow-up. These visits will be conducted by phone and will collect information from participants on vital status and any new cancer diagnoses.
Step 1 has been completed and this results submission pertains to Step 1. Step 2 follow-up is ongoing.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 65 Years  
Sexes Eligible for Study: Female  
Accepts Healthy Volunteers: No  

Criteria

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.

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03382834

Locations

United States, Alabama
Alabama CRS
Birmingham, Alabama, United States, 35294
United States, California
UCLA CARE Center CRS
Los Angeles, California, United States, 90035
Ucsf Hiv/Aids Crs
San Francisco, California, United States, 94110
Harbor-UCLA CRS
Torrance, California, United States, 90502
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80045
United States, District of Columbia
Whitman-Walker Health CRS
Washington, District of Columbia, United States, 20005
United States, Georgia
The Ponce de Leon Center CRS
Atlanta, Georgia, United States, 30308-2012
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States, 60611
United States, Massachusetts
Massachusetts General Hospital CRS (MGH CRS)
Boston, Massachusetts, United States, 02114
United States, New Jersey
New Jersey Medical School Clinical Research Center CRS
Newark, New Jersey, United States, 07103
United States, North Carolina
Chapel Hill CRS
Chapel Hill, North Carolina, United States, 27599
Greensboro CRS
Greensboro, North Carolina, United States, 27401
United States, Ohio
Cincinnati Clinical Research Site
Cincinnati, Ohio, United States, 45219
United States, Pennsylvania
Penn Therapeutics, CRS
Philadelphia, Pennsylvania, United States, 19104
Puerto Rico
Puerto Rico AIDS Clinical Trials Unit CRS
San Juan, Puerto Rico, 00935

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair: Rajesh Gandhi, MD Massachusetts General Hospital (MGH) CRS
Study Chair: Eileen Scully, MD, PhD Johns Hopkins University
More Information

More Information

Additional Information:

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

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)  
ClinicalTrials.gov Identifier: NCT03382834   History of Changes  
Other Study ID Numbers: ACTG A5366  
  38190  
Study First Received: December 19, 2017  
Last Updated: December 17, 2019  

Studies a U.S. FDA-regulated Drug Product: Yes  
Studies a U.S. FDA-regulated Device Product: No  

Additional relevant MeSH terms:
HIV Infections
Tamoxifen
Anti-Retroviral Agents
Vorinostat

ClinicalTrials.gov processed this data on July 08, 2020
This information is provided by ClinicalTrials.gov.