Trial Outcomes & Findings for Reducing the Residual Reservoir of HIV-1 Infected Cells in Patients Receiving Antiretroviral Therapy (NCT NCT02471430)
NCT ID: NCT02471430
Last Updated: 2024-02-28
Results Overview
Cumulative frequency and severity of Grade ≥ 1 adverse events, Grade ≥ 1 lab abnormalities or serious adverse events
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
17 participants
Primary outcome timeframe
All adverse events measured from day 1 until day 28 after administration of the first dose of panobinostat and/or interferon-alpha2a was recorded.
Results posted on
2024-02-28
Participant Flow
Participant milestones
| Measure |
Arm A
Participants in Arm A will receive panobinostat as an oral tablet on days 0, 2, and 4 of the treatment week. The dose of panobinostat will be a 15 mg tablet.
Panobinostat: Panobinostat will be administered orally.
|
Arm B
Participants in Arm B will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0. The dose of pegylated IFN-alpha2a will be 180 mcg. Simultaneously with interferon-alpha2a, a 15 mg tablet of panobinostat will be administered on day 0. Participants will also receive panobinostat as an oral tablet on days 2 and 4 of the treatment week.
Panobinostat: Panobinostat will be administered orally.
Pegylated Interferon-alpha2a: Pegylated Interferon-alpha2a will be administered subcutaneously in one shot.
|
Arm C
Participants in Arm C will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0.The dose of pegylated IFN-alpha2a will be 180 mcg.
Pegylated Interferon-alpha2a: Pegylated Interferon-alpha2a will be administered subcutaneously in one shot.
|
|---|---|---|---|
|
Overall Study
STARTED
|
4
|
9
|
4
|
|
Overall Study
COMPLETED
|
4
|
9
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Reducing the Residual Reservoir of HIV-1 Infected Cells in Patients Receiving Antiretroviral Therapy
Baseline characteristics by cohort
| Measure |
Arm A (Panobinostat-only Arm)
n=4 Participants
Participants in Arm A will receive panobinostat as an oral tablet on days 0, 2, and 4 of the treatment week. The dose of panobinostat will be a 15 mg tablet.
Panobinostat: Panobinostat will be administered orally.
|
Arm B (Panobinostat + IFNa2a Arm)
n=9 Participants
Participants in Arm B will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0. The dose of pegylated IFN-alpha2a will be 180 mcg. Simultaneously with interferon-alpha2a, a 15 mg tablet of panobinostat will be administered on day 0. Participants will also receive panobinostat as an oral tablet on days 2 and 4 of the treatment week.
Panobinostat: Panobinostat will be administered orally.
Pegylated Interferon-alpha2a: Pegylated Interferon-alpha2a will be administered subcutaneously in one shot.
|
Arm C (IFN-a2a-only Arm)
n=4 Participants
Participants in Arm C will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0.The dose of pegylated IFN-alpha2a will be 180 mcg.
Pegylated Interferon-alpha2a: Pegylated Interferon-alpha2a will be administered subcutaneously in one shot.
|
Total
n=17 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Continuous
|
49.5 years
n=5 Participants
|
40.4 years
n=7 Participants
|
43.2 years
n=5 Participants
|
43.2 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=5 Participants
|
9 participants
n=7 Participants
|
4 participants
n=5 Participants
|
17 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: All adverse events measured from day 1 until day 28 after administration of the first dose of panobinostat and/or interferon-alpha2a was recorded.Population: all study participants
Cumulative frequency and severity of Grade ≥ 1 adverse events, Grade ≥ 1 lab abnormalities or serious adverse events
Outcome measures
| Measure |
Arm A
n=4 Participants
Participants in Arm A will receive panobinostat as an oral tablet on days 0, 2, and 4 of the treatment week. The dose of panobinostat will be a 15 mg tablet.
Panobinostat: Panobinostat will be administered orally.
|
Arm B
n=9 Participants
Participants in Arm B will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0. The dose of pegylated IFN-alpha2a will be 180 mcg. Simultaneously with interferon-alpha2a, a 15 mg tablet of panobinostat will be administered on day 0. Participants will also receive panobinostat as an oral tablet on days 2 and 4 of the treatment week.
Panobinostat: Panobinostat will be administered orally.
Pegylated Interferon-alpha2a: Pegylated Interferon-alpha2a will be administered subcutaneously in one shot.
|
Arm C
n=4 Participants
Participants in Arm C will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0.The dose of pegylated IFN-alpha2a will be 180 mcg.
Pegylated Interferon-alpha2a: Pegylated Interferon-alpha2a will be administered subcutaneously in one shot.
|
|---|---|---|---|
|
Occurrence of Grade ≥ 1 Adverse Events (AEs)
|
5 events
|
26 events
|
4 events
|
PRIMARY outcome
Timeframe: Measured through week 4 after administration of panobinostat and/or interferon-alpha2aPopulation: entire study population
Operational measurement of CD4 T cells harboring genome-intact HIV-1 DNA, determined by the IPDA assay.
Outcome measures
| Measure |
Arm A
n=4 Participants
Participants in Arm A will receive panobinostat as an oral tablet on days 0, 2, and 4 of the treatment week. The dose of panobinostat will be a 15 mg tablet.
Panobinostat: Panobinostat will be administered orally.
|
Arm B
n=9 Participants
Participants in Arm B will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0. The dose of pegylated IFN-alpha2a will be 180 mcg. Simultaneously with interferon-alpha2a, a 15 mg tablet of panobinostat will be administered on day 0. Participants will also receive panobinostat as an oral tablet on days 2 and 4 of the treatment week.
Panobinostat: Panobinostat will be administered orally.
Pegylated Interferon-alpha2a: Pegylated Interferon-alpha2a will be administered subcutaneously in one shot.
|
Arm C
n=4 Participants
Participants in Arm C will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0.The dose of pegylated IFN-alpha2a will be 180 mcg.
Pegylated Interferon-alpha2a: Pegylated Interferon-alpha2a will be administered subcutaneously in one shot.
|
|---|---|---|---|
|
Change in CD4 T Cell-Associated Proviral HIV-1 DNA From Baseline
baseline
|
32.6 HIV copies per million CD4 T cells
Standard Error 14.1
|
179 HIV copies per million CD4 T cells
Standard Error 130
|
24 HIV copies per million CD4 T cells
Standard Error 18.3
|
|
Change in CD4 T Cell-Associated Proviral HIV-1 DNA From Baseline
day 28
|
44.7 HIV copies per million CD4 T cells
Standard Error 20.2
|
108.4 HIV copies per million CD4 T cells
Standard Error 79.8
|
18.7 HIV copies per million CD4 T cells
Standard Error 12.5
|
SECONDARY outcome
Timeframe: measured after last dose of PBT on day 4Population: entire study cohort
CD4 T cells expressing acetylated H3, determined by flow cytometry.
Outcome measures
| Measure |
Arm A
n=4 Participants
Participants in Arm A will receive panobinostat as an oral tablet on days 0, 2, and 4 of the treatment week. The dose of panobinostat will be a 15 mg tablet.
Panobinostat: Panobinostat will be administered orally.
|
Arm B
n=9 Participants
Participants in Arm B will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0. The dose of pegylated IFN-alpha2a will be 180 mcg. Simultaneously with interferon-alpha2a, a 15 mg tablet of panobinostat will be administered on day 0. Participants will also receive panobinostat as an oral tablet on days 2 and 4 of the treatment week.
Panobinostat: Panobinostat will be administered orally.
Pegylated Interferon-alpha2a: Pegylated Interferon-alpha2a will be administered subcutaneously in one shot.
|
Arm C
n=4 Participants
Participants in Arm C will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0.The dose of pegylated IFN-alpha2a will be 180 mcg.
Pegylated Interferon-alpha2a: Pegylated Interferon-alpha2a will be administered subcutaneously in one shot.
|
|---|---|---|---|
|
Change From Baseline in Histone H3 Acetylation in CD4 T Cells
baseline
|
2 Percentage of cells
Standard Error 0.64
|
3.1 Percentage of cells
Standard Error 0.76
|
5.5 Percentage of cells
Standard Error 1.47
|
|
Change From Baseline in Histone H3 Acetylation in CD4 T Cells
day 4
|
23.2 Percentage of cells
Standard Error 17.15
|
14.7 Percentage of cells
Standard Error 3.2
|
8.3 Percentage of cells
Standard Error 3.7
|
SECONDARY outcome
Timeframe: measured after last dose of PBT on day 4Population: entire study population
total HIV-1 RNA per ug of RNA in CD4 T cells
Outcome measures
| Measure |
Arm A
n=4 Participants
Participants in Arm A will receive panobinostat as an oral tablet on days 0, 2, and 4 of the treatment week. The dose of panobinostat will be a 15 mg tablet.
Panobinostat: Panobinostat will be administered orally.
|
Arm B
n=9 Participants
Participants in Arm B will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0. The dose of pegylated IFN-alpha2a will be 180 mcg. Simultaneously with interferon-alpha2a, a 15 mg tablet of panobinostat will be administered on day 0. Participants will also receive panobinostat as an oral tablet on days 2 and 4 of the treatment week.
Panobinostat: Panobinostat will be administered orally.
Pegylated Interferon-alpha2a: Pegylated Interferon-alpha2a will be administered subcutaneously in one shot.
|
Arm C
n=4 Participants
Participants in Arm C will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0.The dose of pegylated IFN-alpha2a will be 180 mcg.
Pegylated Interferon-alpha2a: Pegylated Interferon-alpha2a will be administered subcutaneously in one shot.
|
|---|---|---|---|
|
Change From Baseline in Levels of CD4 T Cell-associated HIV-1 RNA
baseline
|
1055.6 HIV RNA copies/ug of RNA
Standard Error 306.9
|
630.6 HIV RNA copies/ug of RNA
Standard Error 279.3
|
772.5 HIV RNA copies/ug of RNA
Standard Error 302.5
|
|
Change From Baseline in Levels of CD4 T Cell-associated HIV-1 RNA
day 4
|
1611.2 HIV RNA copies/ug of RNA
Standard Error 596.6
|
1138.4 HIV RNA copies/ug of RNA
Standard Error 583.1
|
958.8 HIV RNA copies/ug of RNA
Standard Error 296
|
SECONDARY outcome
Timeframe: measured after last dose of PBT on day 4Population: entire study population
the proportion of NK cells expressing NKp30
Outcome measures
| Measure |
Arm A
n=4 Participants
Participants in Arm A will receive panobinostat as an oral tablet on days 0, 2, and 4 of the treatment week. The dose of panobinostat will be a 15 mg tablet.
Panobinostat: Panobinostat will be administered orally.
|
Arm B
n=9 Participants
Participants in Arm B will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0. The dose of pegylated IFN-alpha2a will be 180 mcg. Simultaneously with interferon-alpha2a, a 15 mg tablet of panobinostat will be administered on day 0. Participants will also receive panobinostat as an oral tablet on days 2 and 4 of the treatment week.
Panobinostat: Panobinostat will be administered orally.
Pegylated Interferon-alpha2a: Pegylated Interferon-alpha2a will be administered subcutaneously in one shot.
|
Arm C
n=4 Participants
Participants in Arm C will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0.The dose of pegylated IFN-alpha2a will be 180 mcg.
Pegylated Interferon-alpha2a: Pegylated Interferon-alpha2a will be administered subcutaneously in one shot.
|
|---|---|---|---|
|
Change From Baseline in Frequency of Activated NKp30+ NK Cells.
day 4
|
23 percentage of cells
Standard Error 1.4
|
37.8 percentage of cells
Standard Error 4
|
25.5 percentage of cells
Standard Error 5.6
|
|
Change From Baseline in Frequency of Activated NKp30+ NK Cells.
baseline
|
22.8 percentage of cells
Standard Error 0.9
|
30.9 percentage of cells
Standard Error 3.2
|
21.4 percentage of cells
Standard Error 4.2
|
Adverse Events
Arm A
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Arm B
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Arm C
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Arm A
n=4 participants at risk
Participants in Arm A will receive panobinostat as an oral tablet on days 0, 2, and 4 of the treatment week. The dose of panobinostat will be a 15 mg tablet.
Panobinostat: Panobinostat will be administered orally.
|
Arm B
n=9 participants at risk
Participants in Arm B will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0. The dose of pegylated IFN-alpha2a will be 180 mcg. Simultaneously with interferon-alpha2a, a 15 mg tablet of panobinostat will be administered on day 0. Participants will also receive panobinostat as an oral tablet on days 2 and 4 of the treatment week.
Panobinostat: Panobinostat will be administered orally.
Pegylated Interferon-alpha2a: Pegylated Interferon-alpha2a will be administered subcutaneously in one shot.
|
Arm C
n=4 participants at risk
Participants in Arm C will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0.The dose of pegylated IFN-alpha2a will be 180 mcg.
Pegylated Interferon-alpha2a: Pegylated Interferon-alpha2a will be administered subcutaneously in one shot.
|
|---|---|---|---|
|
General disorders
body aches
|
0.00%
0/4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
44.4%
4/9 • Number of events 4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
25.0%
1/4 • Number of events 1 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
|
General disorders
fatigue
|
0.00%
0/4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
66.7%
6/9 • Number of events 6 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
25.0%
1/4 • Number of events 1 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
|
Nervous system disorders
paresthesia
|
0.00%
0/4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
11.1%
1/9 • Number of events 1 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
0.00%
0/4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
|
Gastrointestinal disorders
nausea
|
25.0%
1/4 • Number of events 1 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
22.2%
2/9 • Number of events 2 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
25.0%
1/4 • Number of events 1 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
|
General disorders
fever
|
0.00%
0/4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
22.2%
2/9 • Number of events 2 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
0.00%
0/4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
|
General disorders
chills
|
0.00%
0/4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
11.1%
1/9 • Number of events 1 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
0.00%
0/4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
|
Gastrointestinal disorders
diarrhea
|
0.00%
0/4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
33.3%
3/9 • Number of events 3 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
0.00%
0/4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
|
Blood and lymphatic system disorders
neutropenia
|
0.00%
0/4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
33.3%
3/9 • Number of events 3 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
0.00%
0/4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
|
Gastrointestinal disorders
vomiting
|
0.00%
0/4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
11.1%
1/9 • Number of events 1 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
0.00%
0/4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
|
Gastrointestinal disorders
Loose stool
|
50.0%
2/4 • Number of events 2 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
11.1%
1/9 • Number of events 1 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
0.00%
0/4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
|
Renal and urinary disorders
increase serum creatinine
|
25.0%
1/4 • Number of events 1 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
0.00%
0/9 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
0.00%
0/4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
|
Cardiac disorders
ECG changes
|
25.0%
1/4 • Number of events 1 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
0.00%
0/9 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
0.00%
0/4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
|
Nervous system disorders
headache
|
0.00%
0/4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
11.1%
1/9 • Number of events 1 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
25.0%
1/4 • Number of events 1 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
|
Skin and subcutaneous tissue disorders
rash
|
0.00%
0/4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
11.1%
1/9 • Number of events 1 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
0.00%
0/4 • 3 years
Adverse event definition is as in clinicaltrials.gov
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place