Romidepsin Plus 3BNC117 Phase 2a Study
Condition: Human Immunodeficiency Virus (HIV)
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Intervention: 3BNC117; Romidepsin
Intervention description: Intravenous Infusion of 3BNC117; Intravenous Infusion of Romidepsin
Intervention MeSH terms: Romidepsin; Histone Deacetylase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Romidepsin; 3BNC117; Broadly neutralizing antibody

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.
    

Eligibility 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.