Romidepsin Plus 3BNC117 Phase 2a Study (ROADMAP)
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|ClinicalTrials.gov Identifier: NCT02850016|
Recruitment Status : Recruiting
First Posted : July 29, 2016
Last Update Posted : April 17, 2018
|Condition or disease||Intervention/treatment||Phase|
|Human Immunodeficiency Virus (HIV)||Drug: 3BNC117 Drug: Romidepsin||Phase 2|
This is a randomized interventional phase 2a trial of 3BNC117 and romidepsin in human immunodeficiency (HIV-1) infected patients on ART, conducted as a multi-center study at the Department of Infectious Diseases, Aarhus University Hospital, Denmark, the Rockefeller University Hospital, USA, and the University Hospital of Cologne, Germany.
Participants will be randomized 1:1 in a non-blinded fashion to receive one of two regimens:
A) Two treatment cycles each consisting of one 3BNC117 infusion (30mg/kg) + three romidepsin infusions (5mg/m2); or
B) Two treatment cycles each consisting of three romidepsin infusions (5mg/m2).
ART will be discontinued 16 weeks after the start of the second treatment cycle (analytical treatment interruption, ATI) and subjects will be monitored weekly for safety and viral rebound. The targeted enrollment is 30 subjects (15 per arm).
Leukapheresis will be performed before and after the two treatment cycles to guarantee sufficient material to investigate changes in the reservoir after the interventions.
The following criteria will require resumption of ART:
- CD4+ T cell-count <350 cells/mm³ (confirmed by repeat measurement)
- 2 consecutive plasma HIV-1 RNA measurements ≥ 200 copies/mL or above their setpoint viremia (if documented)
- Subject request
- Continued ART interruption will, in the opinion of the investigator or study advisers, pose an unacceptable risk to the subject.
If HIV-1 RNA remains undetectable at week 36, subjects will be offered to continue off ART with close monitoring, in conjunction with the subject's primary medical provider, as long as HIV-1 viral rebound does not occur. ART resumption will follow same criteria as detailed above. All subjects will be followed for a total of 48 weeks from enrollment.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2a, Randomized Study of Romidepsin With or Without 3BNC117 to Evaluate the Effects on the HIV-1 Reservoir (ROADMAP)|
|Actual Study Start Date :||January 6, 2017|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||December 2019|
Experimental: Group A
Two treatment cycles each consisting of 3BNC117 infusions (30mg/kg) + three romidepsin infusions (5mg/m2). 3BNC117 will be administered on Days 0 and 56. Romidepsin will be administered on days 2, 9, 16, 58, 65, and 72 .
Intravenous Infusion of 3BNC117
Other Name: Monoclonal AntibodyDrug: Romidepsin
Intravenous Infusion of Romidepsin
Other Name: HDAC inhibitor
Experimental: Group B
Two treatment cycles each consisting of three romidepsin infusions (5mg/m2). Romidepsin will be administered on days 0, 7, 14, 56, 63, and 70 .
Intravenous Infusion of Romidepsin
Other Name: HDAC inhibitor
- Days to viral rebound during analytical treatment interruption (ATI) [ Time Frame: Week 24 to Week 36 ]Viral rebound is defined as HIV-1 RNA ≥ 200 copies/mL on 2 consecutive measurements during ATI. If viral rebound occurs, the date of the first measurement of HIV-1 RNA ≥ 200 copies/mL will be defined as "date of viral rebound
- Days to reinitiation of ART in participants who restart ART before viral rebound. [ Time Frame: Week 24 to Week 36 ]
- Number of of adverse events (AE), serious adverse events (SAE), and serious unexpected serious adverse reactions (SUSAR). [ Time Frame: 48 weeks ]
- Size of the functional, latent HIV-1 reservoir [ Time Frame: Day -14 and Day 154 ]As determined by the number of infectious units per 106 resting memory CD4+ T cells (IUPM) using a viral outgrowth assay before and after therapy. Post therapy measurements will occur after the second cycle, just before ATI.
- Size of the proviral HIV-1 reservoir [ Time Frame: 48 weeks ]Determined by total HIV-1 DNA and episomal HIV-1 DNA (2-LTR) in circulating total CD4+ T cells at baseline, after each romidepsin cycle, prior to the ATI period (week 24), and at the end of the study (week 48).
- Plasma HIV-1 RNA [ Time Frame: 48 weeks ]As measured by a routine clinical assay (Cobas Taqman; detection limit 20 copies/mL), a transcription mediated amplification (TMA)-based assay (detection limit 12 copies/ml) and/or a single copy assay (detection limit 1-2 copies/mL)
- HIV-1 transcriptional activity as determined by unspliced HIV-1 RNA in circulating total CD4+ T cells. [ Time Frame: 48 weeks ]
- Phylogenetically compare viruses grown from PBMCs collected from participants while on ART to rebound viruses collected after ART interruption. [ Time Frame: 48 weeks ]
- Plasma cytokine and immune activation biomarker levels. [ Time Frame: 48 weeks ]
- Change from baseline in the capacity of NK and CD8+ T cells to mediate inhibition of viral replication ex vivo. [ Time Frame: 48 weeks ]
- Absolute cell counts T and NK cells [ Time Frame: 48 weeks ]using standard cell marker panels by flow cytometry (e.g. CD3, CD4, CD8, CD45RA, CCR7 for T cells and CD16/CD56 for NK cells).
- Phenotypic characteristics for T and NK cells [ Time Frame: 48 weeks ]Functional properties of cytotoxic T cells and NK cells will be investigated by analyzing cytokine secretion properties (e.g. IL-2, IFN-γ, TNF-α) and surface expression of CD107a/b as a surrogate marker of cytotoxic activities. CD69, CD161, NKp46, NKG2, and CD85J expression will be analysed on NK cells.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02850016
|Contact: Recruitment Specialistemail@example.com|
|United States, New York|
|The Rockefeller University||Recruiting|
|New York, New York, United States, 10065|
|Contact: Katelyn Bastert 800-782-2737 firstname.lastname@example.org|
|Principal Investigator: Marina Caskey, MD|
|Aarhus University Hospital||Recruiting|
|Contact: Ole Sogaard, MD, PhD +45 7845 2842 email@example.com|
|Principal Investigator: Ole Sogaard, MD, PhD|
|University of Cologne||Recruiting|
|Cologne, Germany, 50937|
|Contact: Gisela Kremer, RN +41-221-478-3324 firstname.lastname@example.org|
|Principal Investigator: Gerd Kaetkenheuer, MD|
|Principal Investigator:||Marina Caskey, MD||Rockefeller University|