Romidepsin Plus 3BNC117 Phase 2a Study

• Status: Completed
• Trial end date: 2020-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rockefeller University
• Collaborators: Aarhus University Hospital; University Hospital of Cologne
• Treatments: Antibodies; Histone Deacetylase Inhibitors; Romidepsin

Criteria

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.