Status and phase
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About
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.
Full 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:
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.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
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:
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.
Primary purpose
Allocation
Interventional model
Masking
48 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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