Human Immunodeficiency Virus (HIV) Clinical Trial
— ROADMAPOfficial title:
A Phase 2a, Randomized Study of Romidepsin With or Without 3BNC117 to Evaluate the Effects on the HIV-1 Reservoir (ROADMAP)
Verified date | July 2022 |
Source | Rockefeller University |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 48 |
Est. completion date | December 31, 2020 |
Est. primary completion date | December 31, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
Denmark | Aarhus University Hospital | Aarhus | |
Germany | University of Cologne | Cologne | |
United States | The Rockefeller University | New York | New York |
Lead Sponsor | Collaborator |
---|---|
Rockefeller University | Aarhus University Hospital, University Hospital of Cologne |
United States, Denmark, Germany,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | HIV-1 Transcriptional Activity as Determined by Unspliced HIV-1 RNA (CA usHIV-1 RNA) in Circulating Total CD4+ T Cells. | The median fold-change in cell-associated unspliced HIV-1 RNA concentrations after romidepsin administration across all infusions | baseline and week 24 | |
Primary | Days to Viral Rebound During Analytical Treatment Interruption (ATI) | 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 | Week 24 to Week 36 | |
Secondary | Number of of Adverse Events (AE), Serious Adverse Events (SAE), and Serious Unexpected Serious Adverse Reactions (SUSAR). | The occurrence of adverse events was assessed during each follow up visit. Adverse events of grades 1 or higher were reported. | 48 weeks | |
Secondary | Change in the Size of the Proviral HIV-1 Reservoir | Determined by total HIV-1 DNA and episomal HIV-1 DNA (2-LTR) in circulating total CD4+ T cells at baseline and prior to the ATI period (week 24). | baseline and week 24 | |
Secondary | Plasma HIV-1 RNA | 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) | 48 weeks |
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