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Romidepsin Plus 3BNC117 Phase 2a Study (ROADMAP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02850016
Recruitment Status : Completed
First Posted : July 29, 2016
Last Update Posted : February 4, 2021
University Hospital of Cologne
Aarhus University Hospital
Information provided by (Responsible Party):
Rockefeller University

Tracking Information
First Submitted Date  ICMJE July 26, 2016
First Posted Date  ICMJE July 29, 2016
Last Update Posted Date February 4, 2021
Actual Study Start Date  ICMJE January 6, 2017
Actual Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 26, 2016)
  • 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2016)
  • 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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 26, 2016)
  • 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.
Original Other Pre-specified Outcome Measures Same as current
Descriptive Information
Brief Title  ICMJE Romidepsin Plus 3BNC117 Phase 2a Study
Official Title  ICMJE A Phase 2a, Randomized Study of Romidepsin With or Without 3BNC117 to Evaluate the Effects on the HIV-1 Reservoir (ROADMAP)
Brief Summary The aim of this protocol is to evaluate the effects of romidepsin plus 3BNC117 or romidepsin alone on delaying or preventing viral rebound in ART-treated HIV-1-infected individuals during an analytical interruption of ART.
Detailed Description

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Human Immunodeficiency Virus (HIV)
Intervention  ICMJE
  • Drug: 3BNC117
    Intravenous Infusion of 3BNC117
    Other Name: Monoclonal Antibody
  • Drug: Romidepsin
    Intravenous Infusion of Romidepsin
    Other Name: HDAC inhibitor
Study Arms  ICMJE
  • 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 .
    • Drug: 3BNC117
    • Drug: Romidepsin
  • 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 .
    Intervention: Drug: Romidepsin
Publications * Valente PK, Wu Y, Cohen YZ, Caskey M, Meyers K. Behavioral and social science research to support development of educational materials for clinical trials of broadly neutralizing antibodies for HIV treatment and prevention. Clin Trials. 2021 Feb;18(1):17-27. doi: 10.1177/1740774520948042. Epub 2020 Aug 24.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 3, 2021)
Original Estimated Enrollment  ICMJE
 (submitted: July 26, 2016)
Actual Study Completion Date  ICMJE December 31, 2020
Actual Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adults age 18-65 years with documented HIV-1 infection
  • CD4+ T-cell count >500 cells/mm3 at screening
  • On ART for a minimum of 24 months and HIV-1 RNA plasma level of < 50 copies/ml by standard assays for at least 18 months (a single viral load measurement > 50 but < 500 copies/ml during this time period is allowable).
  • Individuals on protease inhibitor or NNRTI-based regimens, or regimens containing cobicistat must be willing to switch to an integrase-inhibitor-based regimen (raltegravir or dolutegravir) prior to enrollment.

Exclusion Criteria:

  • Use of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the investigators within the last 6 months
  • Pregnancy as determined by a positive urine or serum beta-hCG.
  • Participant unwilling to use two reliable contraception methods (i.e. condom with spermicide, diaphragm with spermicide, progestin-only containing intrauterine device (IUD) (eg, Mirena, Implanon, Nuva Ring), non-estrogen containing formulations of hormonal birth control drugs with condom) for the study duration.
  • Currently breast-feeding.
  • History of resistance to 2 or more classes of antiretroviral medications
  • Any medical, psychiatric, social, or occupational condition that, as judged by the investigators, would interfere with the evaluation of study objectives (such as severe alcohol or drug abuse, dementia).
  • Acute or chronic hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.
  • A history of AIDS-defining illness within 3 years prior to enrollment.
  • History of B-cell lymphoma, including CNS lymphoma
  • CD4 nadir < 200 cells/mm3
  • History of significant coronary artery disease, myocardial infarction, percutaneous coronary intervention with placement of cardiac stents, or family history of sudden death at age < 50 years.
  • ECG at screening that shows QTc >450 msec when calculated using the Fridericia formula from either lead V3 or V4, pathological Q-waves (Q-wave > 40 msec or depth > 0.4-0.5 mV), evidence of a ventricular pre-excitation syndromes, complete or incomplete LBBB or RBBB, second or third degree heart block, QRS duration > 120 msec, or bradycardia defined by sinus rate < 50 bps
  • Use of QT-prolonging medication, renal or hepatic disease, structural heart disease or left ventricular dysfunction
  • Any symptomatic or asymptomatic arrhythmia excluding sinus arrhythmia and bradycardia ≥ 50 bps.
  • Laboratory abnormalities in the parameters listed below:

    1. Absolute neutrophil count ≤ 1,000 cells/μl
    2. Hemoglobin < 11 gm/dL
    3. Platelet count < 125,000 cells/μl
    4. Alanine Aminotransferase (ALT) ≥ 1.25 x ULN
    5. Aspartate Aminotransferase (AST) ≥ 1.25 x ULN
    6. Total bilirubin > 1.0 ULN
    7. Creatinine > 1.0 ULN
  • Any vaccination within 14 days prior to 3BNC117 administration
  • Receipt of any therapeutic HIV vaccine in the past
  • Receipt of any monoclonal antibody or HDAC inhibitor of any kind in the past.
  • Participation in another clinical study of an investigational product currently or within past 12 weeks, or expected participation during this study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark,   Germany,   United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02850016
Other Study ID Numbers  ICMJE MCA-0896
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Rockefeller University
Study Sponsor  ICMJE Rockefeller University
Collaborators  ICMJE
  • University Hospital of Cologne
  • Aarhus University Hospital
Investigators  ICMJE
Principal Investigator: Marina Caskey, MD Rockefeller University
PRS Account Rockefeller University
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP