HIV infection MedDRA version: 20.0 Level: LLT Classification code 10020180 Term: HIV positive System Organ Class: 100000004848 MedDRA version: 20.1 Level: PT Classification code 10020161 Term: HIV infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: Istodax
Product Name: Romidepsin
Pharmaceutical Form: Infusion
INN or Proposed INN: ROMIDEPSIN
Current Sponsor code: MCA-0896
Other descriptive name: Istodax
Concentration unit: mg/m2 mill
Sponsors
Rockefeller University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Adults age 18-65 years with documented HIV-1 infection 2) CD4+ T-cell count >500 cells/mm3 at screening 3) On ART for a minimum of 18 months and HIV-1 RNA plasma level of 50 but =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Use of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the investigators within the last 6 months 2) Pregnancy as determined by a positive urine beta-hCG. 3) Participant unwilling to use two reliable contraception methods (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom) for the study duration. 4) Currently breast-feeding. 5) History of resistance to 2 or more classes of antiretroviral medication 6) 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). 7) 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. 8) Receipt of an HDAC inhibitor or 3BNC117 in the past 2 years. 9) Have a history of AIDS-defining illness within 3 years prior to enrollment. 10) History of significant coronary artery disease, myocardial infarction, percutaneous coronary intervention with placement of cardiac stents. 11) ECG at screening that shows QTc >450 msec when calculated using the Fridericia formula from either lead V3 or V4. 12) Use of Coumadin or Coumadin derivatives 13) Laboratory abnormalities in the parameters listed below: 13a) Absolute neutrophil count = 1,300 13b) Hemoglobin = 10 gm/dL 13c) Platelet count = 125,000 13d) ALT = 2.0 x ULN 13e) AST = 2.0 x ULN 13f) Total bilirubin = 2.0 x ULN (for participants on atazanavir, a total bilirubin up to 3 x ULN is allowable) 13g) eGFR < 60 mL/min/1.73m2 14) Any vaccination within 14 days prior to 3BNC117 administration 15) Receipt of any therapeutic HIV vaccine in the past 16) Receipt of any monoclonal antibody therapy of any kind in the past 2 years 17) Participation in another clinical study of an investigational product currently or within past 12 weeks, or expected participation during this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the effects of romidepsin plus 3BNC117 or romidepsin alone on delaying or preventing viral rebound in HIV-1-infected individuals during an analytical interruption of ART. ;Secondary Objective: 1) Evaluate the safety of romidepsin plus 3BNC117 or romidepsin alone in ART-treated HIV-1 infected individuals 2) Evaluate the effects of romidepsin plus 3BNC117 or romidepsin alone on the size of the replication competent HIV-1 reservoir in ART-treated HIV-1-infected individuals; 3) Evaluate the immunomodulatory effects of romidepsin plus 3BNC117 or romidepsin alone in ART-treated HIV-1-infected individuals. ;Primary end point(s): Days to viral rebound during analytic treatment interruption or days to reinitiation of ART in participants who restart ART before viral rebound. Viral rebound is defined as HIV-1 RNA = 200 on 2 consecutive measurements during ATI.;Timepoint(s) of evaluation of this end point: During analytic treatment interruption. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Safety evaluation, as measured by rate and severity of adverse events (AE), serious adverse events (SAE), and serious unexpected serious adverse reactions (SUSAR) 2) Size of the functional, latent HIV-1 reservoir 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. These measurements will be performed in Dr. Siliciano’s laboratory 3) Size of the proviral HIV-1 reservoir as determined by total HIV-1 DNA and episomal HIV-1 DNA (2-LTR) in circulating total CD4+ T cells. 4) Plasma HIV-1 RNA, as measured by a routine clinical assay (Cobas Taqman; detection limit 20 copies/mL) and a transcription mediated amplification (TMA)-based assay.;Timepoint(s) of evaluation of this end point: 1) During trial 2) Before and after therapy 4) During trial | — |
Countries
Denmark, Germany, United States
Contacts
Public ContactOle Søgaard
Dept. of Infectious Diseases
Outcome results
None listed