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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03382834
• Other study ID #: ACTG A5366
• Secondary ID: 38190
• Status: Completed
• Phase: Phase 2
• Start date: April 26, 2018
• Est. completion date: July 27, 2023

Study information

• Verified date: August 2023
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: July 27, 2023
• Est. primary completion date: December 4, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Tamoxifen
20 mg orally
• Vorinostat
400 mg orally
• Antiretroviral drugs
Participants will receive antiretroviral drugs provided by their own doctors. Antiretroviral drugs will not be provided by the study.

Locations

Country	Name	City	State
Puerto Rico	Puerto Rico AIDS Clinical Trials Unit CRS	San Juan
United States	The Ponce de Leon Center CRS	Atlanta	Georgia
United States	University of Colorado Hospital CRS	Aurora	Colorado
United States	Alabama CRS	Birmingham	Alabama
United States	Massachusetts General Hospital CRS (MGH CRS)	Boston	Massachusetts
United States	Chapel Hill CRS	Chapel Hill	North Carolina
United States	Northwestern University CRS	Chicago	Illinois
United States	Cincinnati Clinical Research Site	Cincinnati	Ohio
United States	Greensboro CRS	Greensboro	North Carolina
United States	UCLA CARE Center CRS	Los Angeles	California
United States	New Jersey Medical School Clinical Research Center CRS	Newark	New Jersey
United States	Penn Therapeutics, CRS	Philadelphia	Pennsylvania
United States	Ucsf Hiv/Aids Crs	San Francisco	California
United States	Harbor-UCLA CRS	Torrance	California
United States	Whitman-Walker Health CRS	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Number of Participants With HIV-1 RNA Levels (Measured by Single Copy Assay) Greater or Equal to the Lower Limit of Quantification	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.	Pre-entry, entry, Day 28, Day 35, Day 38 (5 hours post vorinostat), Day 45, Day 65
Secondary	Change From Baseline in Total HIV-1 DNA Levels in CD4+ T Cells	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.	Pre-entry, entry, and Day 38

External 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