Reducing the Residual Reservoir of HIV-1 Infected Cells in Patients Receiving Antiretroviral Therapy (ACTIVATE)
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|ClinicalTrials.gov Identifier: NCT02471430|
Recruitment Status : Recruiting
First Posted : June 15, 2015
Last Update Posted : January 12, 2018
|Condition or disease||Intervention/treatment||Phase|
|HIV Infection||Drug: Panobinostat Drug: Pegylated Interferon-alpha2a||Phase 1 Phase 2|
This study is a prospective, double-arm, randomized, open-label, dose-escalation exploratory clinical trial involving HIV-1 infected participants treated with suppressive combination antiretroviral combination therapy (cART). The primary objective of this study is to evaluate a new strategy for reducing the residual reservoir of HIV-1 infected cells that persists despite treatment with current HIV drugs. The clinical trial is conducted in the Infectious Diseases Clinical Trials Unit (CTU) at the Massachusetts General Hospital.
The study medication includes two agents: Panobinostat is an oral tablet that can reverse HIV-1 latency and awaken HIV from a "sleeping" condition during which it is protected from the human immune system. The second drug is interferon-alpha2a, an injectable cytokine that activates the immune system. The combined use of both agents may lead to immune-mediated elimination of HIV-1 infected cells in which viral latency has been reversed by panobinostat.
All participants will receive one week of treatment with panobinostat (10mg, dosed every second day on Monday, Wednesday, Friday), followed by three weeks off-treatment. Participants will be randomized to receive this treatment course with panobinostat alone (Arm A, 2 participants total), or in combination with pegylated IFN-alpha2a (Arm B, 6 participants total). Subcutaneous injections with pegylated Interferon-alpha2a will be administered at the start of the week-long treatment course, simultaneously with the first dose of panobinostat. ART will be continued during the entire treatment duration in all study participants.
Participants will undergo close monitoring for side effects during the entire time of study participation. The total study duration will be 2 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||31 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I-II Pilot Study to Assess the Safety and Efficacy of Combined Administration With Pegylated Interferon-alpha2a and the Histone Deacetylase Inhibitor (HDACi) Panobinostat for Reducing the Residual Reservoir of HIV-1 Infected Cells in cART-Treated HIV-1 Positive Individuals|
|Study Start Date :||May 2016|
|Estimated Primary Completion Date :||September 2018|
|Estimated Study Completion Date :||February 2020|
Experimental: 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 10 mg tablet.
Panobinostat will be administered orally.
Experimental: 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 10 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 will be administered orally.
Drug: Pegylated Interferon-alpha2a
Pegylated Interferon-alpha2a will be administered subcutaneously in one shot.
Other Name: Pegasys
- Occurrence of Grade ≥ 1 Adverse Events (AEs) [ Time Frame: Measured through 1 month after administration of panobinostat and/or interferon-alpha2a ]Cumulative frequency and severity of Grade ≥ 1 adverse events, Grade ≥ 1 lab abnormalities or serious adverse events
- Change in CD4 T Cell-Associated Proviral HIV-1 DNA from Baseline [ Time Frame: Measured through 1 week after administration of panobinostat and/or interferon-alpha2a ]Operational measurement of HIV-1 reservoir
- Change from baseline in levels of infectious viral units per million CD4 T cells [ Time Frame: Measured through 1 week after study drug administration ]
- Change from baseline in histone H3 acetylation in CD4 T cells [ Time Frame: Measured through 1 week after study drug administration ]
- Change from baseline in levels of CD4 T cell-associated HIV-1 RNA [ Time Frame: Measured through 1 week after study drug administration ]
- Change from baseline in levels of plasma HIV-1 RNA [ Time Frame: Measured through 1 week after study drug administration ]
- Change from baseline in levels of CD4 T cell-associated HIV-1 2-LTR circles and chromosomally integrated proviral HIV-1 DNA [ Time Frame: Measured through 1 week after study drug administration ]
- Change from baseline in levels of HIV-1 DNA in different CD4 T cell subsets (naïve, T memory stem cells, central-memory, effector-memory, terminally-differentiated) [ Time Frame: Measured through 1 week after study drug administration ]
- Change from baseline in frequency and function of innate and adaptive immune effector cell responses [ Time Frame: Measured through 1 week after study drug administration ]
- Change from baseline in levels of cellular and soluble immune activation markers [ Time Frame: Measured through 1 week after study drug administration ]
- Change from baseline in expression patterns of interferon-stimulated genes (ISG) [ Time Frame: Measured through 1 week after study drug administration ]
- Comparison of all immunologically and virological parameters in study participants treated with pegylated Interferon-alpha2a and panobinostat according to HLA class I and IL-28b genotypes [ Time Frame: Measured through 1 week after study drug administration ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02471430
|Contact: Theresa Flynn, MSN, ANPemail@example.com|
|United States, Massachusetts|
|Massachusetts General Hospital CRS (MGH CRS)||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Theresa Flynn, R.N., M.S.N., A.N.P, B.S.N. (617) 724-0072 firstname.lastname@example.org|
|Principal Investigator:||Mathias Lichterfeld, MD, PhD||Massachusetts General Hospital|
|Principal Investigator:||Daniel R Kuritzkes, MD||Massachusetts General Hospital|
|Principal Investigator:||Rajesh T Gandhi, MD||Massachusetts General Hospital|