Overview

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.