Trial Outcomes & Findings for Selective Estrogen Receptor Modulators to Enhance the Efficacy of Viral Reactivation With Histone Deacetylase Inhibitors (NCT NCT03382834)
NCT ID: NCT03382834
Last Updated: 2024-07-03
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
31 participants
Primary outcome timeframe
Measured from study entry through Day 65
Results posted on
2024-07-03
Participant Flow
Participant milestones
| Measure |
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.
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.
|
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.
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.
|
|---|---|---|
|
Step 1
STARTED
|
21
|
10
|
|
Step 1
COMPLETED
|
21
|
9
|
|
Step 1
NOT COMPLETED
|
0
|
1
|
|
Step 2
STARTED
|
21
|
9
|
|
Step 2
COMPLETED
|
17
|
7
|
|
Step 2
NOT COMPLETED
|
4
|
2
|
Reasons for withdrawal
| Measure |
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.
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.
|
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.
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.
|
|---|---|---|
|
Step 1
Lost to Follow-up
|
0
|
1
|
|
Step 2
Death
|
1
|
0
|
|
Step 2
Lost to Follow-up
|
2
|
2
|
|
Step 2
Site Terminated by Sponsor
|
1
|
0
|
Baseline Characteristics
CA-RNA analyses were performed on the efficacy population, defined as the subset of enrolled participants who received full study treatment and did not have ART interruption or confirmed viral load (VL) \>= 200 copies/mL. The definition was expanded by team to exclude 2 participants; one with high pre-entry VL and one with wrong timing of samples.
Baseline characteristics by cohort
| Measure |
Arm A: Tamoxifen + Vorinostat
n=21 Participants
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.
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.
|
Arm B: Vorinostat Alone
n=10 Participants
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.
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.
|
Total
n=31 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
57 years
n=21 Participants
|
55 years
n=10 Participants
|
57 years
n=31 Participants
|
|
Age, Customized
Age categorized · < 50 years
|
2 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
3 Participants
n=31 Participants
|
|
Age, Customized
Age categorized · 50 - 59 years
|
11 Participants
n=21 Participants
|
7 Participants
n=10 Participants
|
18 Participants
n=31 Participants
|
|
Age, Customized
Age categorized · >= 60 years
|
8 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
10 Participants
n=31 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=21 Participants
|
10 Participants
n=10 Participants
|
31 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
6 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
17 Participants
n=21 Participants
|
8 Participants
n=10 Participants
|
25 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
1 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Black or African American
|
11 Participants
n=21 Participants
|
7 Participants
n=10 Participants
|
18 Participants
n=31 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=21 Participants
|
3 Participants
n=10 Participants
|
12 Participants
n=31 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=31 Participants
|
|
Region of Enrollment
Puerto Rico
|
1 participants
n=21 Participants
|
0 participants
n=10 Participants
|
1 participants
n=31 Participants
|
|
Region of Enrollment
United States
|
20 participants
n=21 Participants
|
10 participants
n=10 Participants
|
30 participants
n=31 Participants
|
|
Baseline Cell-associated HIV-1 RNA
|
1.81 log10 copies/million CD4 cells
n=19 Participants • CA-RNA analyses were performed on the efficacy population, defined as the subset of enrolled participants who received full study treatment and did not have ART interruption or confirmed viral load (VL) \>= 200 copies/mL. The definition was expanded by team to exclude 2 participants; one with high pre-entry VL and one with wrong timing of samples.
|
2.5 log10 copies/million CD4 cells
n=8 Participants • CA-RNA analyses were performed on the efficacy population, defined as the subset of enrolled participants who received full study treatment and did not have ART interruption or confirmed viral load (VL) \>= 200 copies/mL. The definition was expanded by team to exclude 2 participants; one with high pre-entry VL and one with wrong timing of samples.
|
2.17 log10 copies/million CD4 cells
n=27 Participants • CA-RNA analyses were performed on the efficacy population, defined as the subset of enrolled participants who received full study treatment and did not have ART interruption or confirmed viral load (VL) \>= 200 copies/mL. The definition was expanded by team to exclude 2 participants; one with high pre-entry VL and one with wrong timing of samples.
|
PRIMARY outcome
Timeframe: Measured from study entry through Day 65Population: Enrolled participants who were exposed to study treatment
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.
Outcome measures
| Measure |
Arm A: Tamoxifen + Vorinostat
n=21 Participants
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.
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.
|
Arm B: Vorinostat Alone
n=9 Participants
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.
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.
|
|---|---|---|
|
Proportion of Participants With New Grade 3 or Greater Adverse Events
|
0 proportion of participants
Interval 0.0 to 0.13
|
0 proportion of participants
Interval 0.0 to 0.28
|
PRIMARY outcome
Timeframe: Pre-entry, entry, and Day 38Population: Efficacy population
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.
Outcome measures
| Measure |
Arm A: Tamoxifen + Vorinostat
n=19 Participants
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.
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.
|
Arm B: Vorinostat Alone
n=8 Participants
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.
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.
|
|---|---|---|
|
Change From Baseline in Cell-associated HIV-1 RNA in CD4+ T Cells
|
0.06 log10 copies/million CD4 cells
Interval -0.24 to 0.36
|
0.17 log10 copies/million CD4 cells
Interval -0.15 to 0.5
|
SECONDARY outcome
Timeframe: Pre-entry, entry, Day 28, Day 35, Day 38 (5 hours post vorinostat), Day 45, Day 65Population: Efficacy population
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.
Outcome measures
| Measure |
Arm A: Tamoxifen + Vorinostat
n=19 Participants
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.
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.
|
Arm B: Vorinostat Alone
n=8 Participants
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.
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.
|
|---|---|---|
|
Number of Participants With HIV-1 RNA Levels (Measured by Single Copy Assay) Greater or Equal to the Lower Limit of Quantification
Pre-entry SCA >= LOQ
|
10 Participants
|
6 Participants
|
|
Number of Participants With HIV-1 RNA Levels (Measured by Single Copy Assay) Greater or Equal to the Lower Limit of Quantification
Entry SCA >=LOQ
|
9 Participants
|
3 Participants
|
|
Number of Participants With HIV-1 RNA Levels (Measured by Single Copy Assay) Greater or Equal to the Lower Limit of Quantification
Day 28 SCA >=LOQ
|
11 Participants
|
4 Participants
|
|
Number of Participants With HIV-1 RNA Levels (Measured by Single Copy Assay) Greater or Equal to the Lower Limit of Quantification
Day 35 SCA >=LOQ
|
11 Participants
|
5 Participants
|
|
Number of Participants With HIV-1 RNA Levels (Measured by Single Copy Assay) Greater or Equal to the Lower Limit of Quantification
Day 38 SCA >=LOQ
|
7 Participants
|
5 Participants
|
|
Number of Participants With HIV-1 RNA Levels (Measured by Single Copy Assay) Greater or Equal to the Lower Limit of Quantification
Day 45 SCA >=LOQ
|
9 Participants
|
4 Participants
|
|
Number of Participants With HIV-1 RNA Levels (Measured by Single Copy Assay) Greater or Equal to the Lower Limit of Quantification
Day 65 SCA >=LOQ
|
10 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Pre-entry, entry, and Day 38Population: Efficacy Population
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.
Outcome measures
| Measure |
Arm A: Tamoxifen + Vorinostat
n=19 Participants
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.
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.
|
Arm B: Vorinostat Alone
n=8 Participants
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.
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.
|
|---|---|---|
|
Change From Baseline in Total HIV-1 DNA Levels in CD4+ T Cells
|
0 log10 copies/million CD4 cells
Interval -0.12 to 0.13
|
-0.04 log10 copies/million CD4 cells
Interval -0.33 to 0.25
|
Adverse Events
Arm A: Tamoxifen + Vorinostat
Serious events: 0 serious events
Other events: 3 other events
Deaths: 1 deaths
Arm B: Vorinostat Alone
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Arm A: Tamoxifen + Vorinostat
n=21 participants at risk
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.
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.
|
Arm B: Vorinostat Alone
n=10 participants at risk
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.
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.
|
|---|---|---|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
4.8%
1/21 • From study entry to end of study
The protocol required reporting of all diagnoses, all signs/symptoms/laboratory values Grade ≥ 3, and all diagnoses/signs/symptoms/laboratory values that led to treatment change or met SAE or EAE reporting requirements through Day 65 (Step 1), and all new cancer diagnoses/deaths during the subsequent 240 week long-term safety follow-up (Step 2). For grading, sites referred to the Division of AIDS AE Grading Table, corrected Version 2.1, July 2017.
|
0.00%
0/10 • From study entry to end of study
The protocol required reporting of all diagnoses, all signs/symptoms/laboratory values Grade ≥ 3, and all diagnoses/signs/symptoms/laboratory values that led to treatment change or met SAE or EAE reporting requirements through Day 65 (Step 1), and all new cancer diagnoses/deaths during the subsequent 240 week long-term safety follow-up (Step 2). For grading, sites referred to the Division of AIDS AE Grading Table, corrected Version 2.1, July 2017.
|
|
Nervous system disorders
Dysgeusia
|
4.8%
1/21 • From study entry to end of study
The protocol required reporting of all diagnoses, all signs/symptoms/laboratory values Grade ≥ 3, and all diagnoses/signs/symptoms/laboratory values that led to treatment change or met SAE or EAE reporting requirements through Day 65 (Step 1), and all new cancer diagnoses/deaths during the subsequent 240 week long-term safety follow-up (Step 2). For grading, sites referred to the Division of AIDS AE Grading Table, corrected Version 2.1, July 2017.
|
0.00%
0/10 • From study entry to end of study
The protocol required reporting of all diagnoses, all signs/symptoms/laboratory values Grade ≥ 3, and all diagnoses/signs/symptoms/laboratory values that led to treatment change or met SAE or EAE reporting requirements through Day 65 (Step 1), and all new cancer diagnoses/deaths during the subsequent 240 week long-term safety follow-up (Step 2). For grading, sites referred to the Division of AIDS AE Grading Table, corrected Version 2.1, July 2017.
|
|
General disorders
Thirst
|
4.8%
1/21 • From study entry to end of study
The protocol required reporting of all diagnoses, all signs/symptoms/laboratory values Grade ≥ 3, and all diagnoses/signs/symptoms/laboratory values that led to treatment change or met SAE or EAE reporting requirements through Day 65 (Step 1), and all new cancer diagnoses/deaths during the subsequent 240 week long-term safety follow-up (Step 2). For grading, sites referred to the Division of AIDS AE Grading Table, corrected Version 2.1, July 2017.
|
0.00%
0/10 • From study entry to end of study
The protocol required reporting of all diagnoses, all signs/symptoms/laboratory values Grade ≥ 3, and all diagnoses/signs/symptoms/laboratory values that led to treatment change or met SAE or EAE reporting requirements through Day 65 (Step 1), and all new cancer diagnoses/deaths during the subsequent 240 week long-term safety follow-up (Step 2). For grading, sites referred to the Division of AIDS AE Grading Table, corrected Version 2.1, July 2017.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic squamous cell carcinoma
|
4.8%
1/21 • From study entry to end of study
The protocol required reporting of all diagnoses, all signs/symptoms/laboratory values Grade ≥ 3, and all diagnoses/signs/symptoms/laboratory values that led to treatment change or met SAE or EAE reporting requirements through Day 65 (Step 1), and all new cancer diagnoses/deaths during the subsequent 240 week long-term safety follow-up (Step 2). For grading, sites referred to the Division of AIDS AE Grading Table, corrected Version 2.1, July 2017.
|
0.00%
0/10 • From study entry to end of study
The protocol required reporting of all diagnoses, all signs/symptoms/laboratory values Grade ≥ 3, and all diagnoses/signs/symptoms/laboratory values that led to treatment change or met SAE or EAE reporting requirements through Day 65 (Step 1), and all new cancer diagnoses/deaths during the subsequent 240 week long-term safety follow-up (Step 2). For grading, sites referred to the Division of AIDS AE Grading Table, corrected Version 2.1, July 2017.
|
Additional Information
ACTG Clinicaltrials.gov Coordinator
ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
Phone: 3016283313
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights
- Publication restrictions are in place
Restriction type: OTHER