Reducing the Residual Reservoir of HIV-1 Infected Cells in Patients Receiving Antiretroviral Therapy (ACTIVATE)

• ClinicalTrials.gov Identifier: NCT02471430
• Recruitment Status: Completed
• First Posted: June 15, 2015
• Results First Posted: February 28, 2024
• Last Update Posted: February 28, 2024
• Sponsor: Massachusetts General Hospital
• Collaborators: Novartis; Genentech, Inc.
• Information provided by (Responsible Party): Mathias Lichterfeld, Massachusetts General Hospital

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV Infection
• Interventions: Drug: Panobinostat; Drug: Pegylated Interferon-alpha2a
• Enrollment: 17

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Arm A	Arm B	Arm C
Arm/Group Description	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.	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.	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.
Period Title: Overall Study
Started	4	9	4
Completed	4	9	4
Not Completed	0	0	0

Baseline Characteristics

Arm/Group Title		Arm A (Panobinostat-only Arm)	Arm B (Panobinostat + IFNa2a Arm)	Arm C (IFN-a2a-only Arm)	Total
Arm/Group Description		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.	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.	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 of all reporting groups
Overall Number of Baseline Participants		4	9	4	17
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants	9 participants	4 participants	17 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	4 100.0%	9 100.0%	4 100.0%	17 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	4 participants	9 participants	4 participants	17 participants
		49.5; (41 to 60)	40.4; (26 to 58)	43.2; (35 to 47)	43.2; (26 to 60)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants	9 participants	4 participants	17 participants
	Female	1 25.0%	0 0.0%	2 50.0%	3 17.6%
	Male	3 75.0%	9 100.0%	2 50.0%	14 82.4%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants	9 participants	4 participants	17 participants
	Hispanic or Latino	2 50.0%	5 55.6%	1 25.0%	8 47.1%
	Not Hispanic or Latino	2 50.0%	4 44.4%	3 75.0%	9 52.9%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants	9 participants	4 participants	17 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	1 11.1%	0 0.0%	1 5.9%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	1 25.0%	0 0.0%	2 50.0%	3 17.6%
	White	3 75.0%	8 88.9%	2 50.0%	13 76.5%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	4 participants	9 participants	4 participants	17 participants
		4	9	4	17

Outcome Measures

1. Primary Outcome

Title	Occurrence of Grade ≥ 1 Adverse Events (AEs)
Description	Cumulative frequency and severity of Grade ≥ 1 adverse events, Grade ≥ 1 lab abnormalities or serious adverse events
Time Frame	All adverse events measured from day 1 until day 28 after administration of the first dose of panobinostat and/or interferon-alpha2a was recorded.

Outcome Measure Data

Analysis Population Description

all study participants

Arm/Group Title	Arm A	Arm B	Arm C
Arm/Group Description:	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.	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.	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 Number of Participants Analyzed	4	9	4
Measure Type: Number; Unit of Measure: events
	5	26	4

2. Primary Outcome

Title	Change in CD4 T Cell-Associated Proviral HIV-1 DNA From Baseline
Description	Operational measurement of CD4 T cells harboring genome-intact HIV-1 DNA, determined by the IPDA assay.
Time Frame	Measured through week 4 after administration of panobinostat and/or interferon-alpha2a

Outcome Measure Data

Analysis Population Description

entire study population

Arm/Group Title	Arm A	Arm B	Arm C
Arm/Group Description:	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.	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.	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 Number of Participants Analyzed	4	9	4
Mean (Standard Error); Unit of Measure: HIV copies per million CD4 T cells
baseline	32.6 (14.1)	179 (130)	24 (18.3)
day 28	44.7 (20.2)	108.4 (79.8)	18.7 (12.5)

3. Secondary Outcome

Title	Change From Baseline in Histone H3 Acetylation in CD4 T Cells
Description	CD4 T cells expressing acetylated H3, determined by flow cytometry.
Time Frame	measured after last dose of PBT on day 4

Outcome Measure Data

Analysis Population Description

entire study cohort

Arm/Group Title	Arm A	Arm B	Arm C
Arm/Group Description:	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.	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.	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 Number of Participants Analyzed	4	9	4
Mean (Standard Error); Unit of Measure: Percentage of cells
baseline	2 (0.64)	3.1 (0.76)	5.5 (1.47)
day 4	23.2 (17.15)	14.7 (3.2)	8.3 (3.7)

4. Secondary Outcome

Title	Change From Baseline in Levels of CD4 T Cell-associated HIV-1 RNA
Description	total HIV-1 RNA per ug of RNA in CD4 T cells
Time Frame	measured after last dose of PBT on day 4

Outcome Measure Data

Analysis Population Description

entire study population

Arm/Group Title	Arm A	Arm B	Arm C
Arm/Group Description:	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.	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.	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 Number of Participants Analyzed	4	9	4
Mean (Standard Error); Unit of Measure: HIV RNA copies/ug of RNA
baseline	1055.6 (306.9)	630.6 (279.3)	772.5 (302.5)
day 4	1611.2 (596.6)	1138.4 (583.1)	958.8 (296)

5. Secondary Outcome

Title	Change From Baseline in Frequency of Activated NKp30+ NK Cells.
Description	the proportion of NK cells expressing NKp30
Time Frame	measured after last dose of PBT on day 4

Outcome Measure Data

Analysis Population Description

entire study population

Arm/Group Title	Arm A	Arm B	Arm C
Arm/Group Description:	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.	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.	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 Number of Participants Analyzed	4	9	4
Mean (Standard Error); Unit of Measure: percentage of cells
baseline	22.8 (0.9)	30.9 (3.2)	21.4 (4.2)
day 4	23 (1.4)	37.8 (4)	25.5 (5.6)

Adverse Events

Time Frame	3 years
Adverse Event Reporting Description	Adverse event definition is as in clinicaltrials.gov
Arm/Group Title	Arm A		Arm B		Arm C
Arm/Group Description	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.		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.		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.
All-Cause Mortality
	Arm A		Arm B		Arm C
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/4 (0.00%)		0/9 (0.00%)		0/4 (0.00%)
Serious Adverse Events
	Arm A		Arm B		Arm C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0.00%)		0/9 (0.00%)		0/4 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Arm A		Arm B		Arm C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/4 (75.00%)		9/9 (100.00%)		4/4 (100.00%)
Blood and lymphatic system disorders
neutropenia †	0/4 (0.00%)	0	3/9 (33.33%)	3	0/4 (0.00%)	0
Cardiac disorders
ECG changes †	1/4 (25.00%)	1	0/9 (0.00%)	0	0/4 (0.00%)	0
Gastrointestinal disorders
nausea †	1/4 (25.00%)	1	2/9 (22.22%)	2	1/4 (25.00%)	1
diarrhea †	0/4 (0.00%)	0	3/9 (33.33%)	3	0/4 (0.00%)	0
vomiting †	0/4 (0.00%)	0	1/9 (11.11%)	1	0/4 (0.00%)	0
Loose stool †	2/4 (50.00%)	2	1/9 (11.11%)	1	0/4 (0.00%)	0
General disorders
body aches †	0/4 (0.00%)	0	4/9 (44.44%)	4	1/4 (25.00%)	1
fatigue †	0/4 (0.00%)	0	6/9 (66.67%)	6	1/4 (25.00%)	1
fever †	0/4 (0.00%)	0	2/9 (22.22%)	2	0/4 (0.00%)	0
chills †	0/4 (0.00%)	0	1/9 (11.11%)	1	0/4 (0.00%)	0
Nervous system disorders
paresthesia †	0/4 (0.00%)	0	1/9 (11.11%)	1	0/4 (0.00%)	0
headache †	0/4 (0.00%)	0	1/9 (11.11%)	1	1/4 (25.00%)	1
Renal and urinary disorders
increase serum creatinine †	1/4 (25.00%)	1	0/9 (0.00%)	0	0/4 (0.00%)	0
Skin and subcutaneous tissue disorders
rash †	0/4 (0.00%)	0	1/9 (11.11%)	1	0/4 (0.00%)	0
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Mathias Lichterfeld
• Organization: Massachusetts General Hospital
• Phone: 617-726-2000
• EMail: mlichterfeld@mgh.harvard.edu

Publications:

Rasmussen TA, Tolstrup M, Brinkmann CR, Olesen R, Erikstrup C, Solomon A, Winckelmann A, Palmer S, Dinarello C, Buzon M, Lichterfeld M, Lewin SR, Ostergaard L, Sogaard OS. Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial. Lancet HIV. 2014 Oct;1(1):e13-21. doi: 10.1016/S2352-3018(14)70014-1. Epub 2014 Sep 15.

• Responsible Party: Mathias Lichterfeld, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT02471430
• Other Study ID Numbers: U01 2015P000858; 12049 ( Other Identifier: Division of AIDS (DAIDS-ES) )
• First Submitted: June 11, 2015
• First Posted: June 15, 2015
• Results First Submitted: January 5, 2024
• Results First Posted: February 28, 2024
• Last Update Posted: February 28, 2024