Selective Estrogen Receptor Modulators to Enhance the Efficacy of Viral Reactivation With Histone Deacetylase Inhibitors
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| ClinicalTrials.gov Identifier: NCT03382834 |
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Recruitment Status :
Active, not recruiting
First Posted : December 26, 2017
Results First Posted : December 18, 2019
Last Update Posted : February 8, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| HIV Infections | Drug: Tamoxifen Drug: Vorinostat Drug: Antiretroviral drugs | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 31 participants |
| 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 |
| Actual Study Start Date : | April 26, 2018 |
| Actual Primary Completion Date : | December 4, 2018 |
| Estimated Study Completion Date : | June 30, 2023 |
| Arm | Intervention/treatment |
|---|---|
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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.
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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. |
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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.
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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. |
- 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.
- 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.
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| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03382834
| 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, Pennsylvania | |
| Penn Therapeutics, CRS | |
| Philadelphia, Pennsylvania, United States, 19104 | |
| Puerto Rico | |
| Puerto Rico AIDS Clinical Trials Unit CRS | |
| San Juan, Puerto Rico, 00935 | |
| Study Chair: | Rajesh Gandhi, MD | Massachusetts General Hospital (MGH) CRS | |
| Study Chair: | Eileen Scully, MD, PhD | Johns Hopkins University |
Documents provided by National Institute of Allergy and Infectious Diseases (NIAID):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT03382834 |
| Other Study ID Numbers: |
ACTG A5366 38190 ( Registry Identifier: DAIDS-ES Registry Number ) |
| First Posted: | December 26, 2017 Key Record Dates |
| Results First Posted: | December 18, 2019 |
| Last Update Posted: | February 8, 2023 |
| Last Verified: | February 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Individual participant data that underlie results in the publication, after deidentification. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (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." |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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HIV Infections 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 Tamoxifen |
Anti-Retroviral Agents Vorinostat Estrogen Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents, Hormonal Antineoplastic Agents Selective Estrogen Receptor Modulators Estrogen Receptor Modulators Bone Density Conservation Agents Histone Deacetylase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antiviral Agents |