HIV InfectionsPhase 2NCT03382834
Selective Estrogen Receptor Modulators to Enhance the Efficacy of Viral Reactivation With Histone Deacetylase Inhibitors
A Phase 2 study testing Tamoxifen, Vorinostat and Antiretroviral drugs in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- HIV Infections
- What is being tested?
- Tamoxifen, Vorinostat and Antiretroviral drugs
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 15 sitesin 2 countries
- Study dates
- 26 Apr 2018to 27 Jul 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
15 sites in 2 countries.
15 sites in 2 countries
United States14 sites
The Ponce de Leon Center CRS
Atlanta, Georgia, 30308-2012
University of Colorado Hospital CRS
Aurora, Colorado, 80045
Alabama CRS
Birmingham, Alabama, 35294
Massachusetts General Hospital CRS (MGH CRS)
Boston, Massachusetts, 02114
Chapel Hill CRS
Chapel Hill, North Carolina, 27599
Northwestern University CRS
Chicago, Illinois, 60611
Cincinnati Clinical Research Site
Cincinnati, Ohio, 45219
Greensboro CRS
Greensboro, North Carolina, 27401
UCLA CARE Center CRS
Los Angeles, California, 90035
New Jersey Medical School Clinical Research Center CRS
Newark, New Jersey, 07103
Penn Therapeutics, CRS
Philadelphia, Pennsylvania, 19104
Ucsf Hiv/Aids Crs
San Francisco, California, 94110
Harbor-UCLA CRS
Torrance, California, 90502
Whitman-Walker Health CRS
Washington D.C., District of Columbia, 20005
Puerto Rico1 site
Puerto Rico AIDS Clinical Trials Unit CRS
San Juan, 00935
About this study
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.
Read the 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 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
- HIV Infections
- Being tested
- Tamoxifen, Vorinostat, Antiretroviral drugs
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TamoxifenDrug
20 mg orally
VorinostatDrug
400 mg orally
Antiretroviral drugsDrug
Participants will receive antiretroviral drugs provided by their own doctors. Antiretroviral drugs will not be provided by the study.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Vorinostat; Drug: Antiretroviral drugs |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: 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.
Measured: 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
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.
Measured: 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
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.
Measured: Pre-entry, entry, and Day 38
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2017
- Study start26 Apr 2018
- Primary completion4 Dec 2018
- Study completion27 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Rajesh Gandhi, MD, Study chair, Massachusetts General Hospital (MGH) CRSEileen Scully, MD, PhD, Study chair, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03382834
- Sponsor's protocol ID
- ACTG A5366
- Other IDs
- 38190
- Status last verified
- Aug 2023
- First submitted
- 19 Dec 2017
- Last updated
- 3 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie results in the publication, after deidentification.
Publications
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.
PubMed 35176755
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Selective Estrogen Receptor Modulators to Enhance the Efficacy of Viral Reactivation With Histone Deacetylase Inhibitors
- ClinicalTrials.gov ID
- NCT03382834
- Acronym / sponsor ID
- ACTG A5366
- Conditions
- HIV Infections
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 26 Apr 2018 (actual)
- Primary completion
- 4 Dec 2018 (actual)
- Study completion
- 27 Jul 2023 (actual)
- First posted
- 26 Dec 2017 (actual)
- Results
- Posted 18 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: Tamoxifen + Vorinostat | Experimental | Drug: Tamoxifen, Drug: Vorinostat, Drug: Antiretroviral drugsFrom 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. |
| Arm B: Vorinostat alone | Active comparator | Drug: Vorinostat, Drug: Antiretroviral drugsDay 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tamoxifen20 mg orally | Drug | Arm A: Tamoxifen + Vorinostat |
| Vorinostat400 mg orally | Drug | Arm A: Tamoxifen + Vorinostat, Arm B: Vorinostat alone |
| Antiretroviral drugsParticipants will receive antiretroviral drugs provided by their own doctors. Antiretroviral drugs will not be provided by the study. | Drug | Arm A: Tamoxifen + Vorinostat, Arm B: Vorinostat alone |
Primary outcome
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.
2 secondary outcomes
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
Change From Baseline in Total HIV-1 DNA Levels in CD4+ T Cells
Time frame: Pre-entry, entry, and Day 38
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35176755Scully 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.
- Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie results in the publication, after deidentification.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rajesh Gandhi, MD study chair
Massachusetts General Hospital (MGH) CRS
Eileen Scully, MD, PhD study chair
Johns Hopkins University
15 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tamoxifen, Vorinostat and Antiretroviral drugs in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Participants With New Grade 3 or Greater Adverse Events (time frame: Measured from study entry through Day 65). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03382834, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2024.