Early Administration of Romidepsin and 3BNC117 in Treatment-naïve HIV Patients Starting ART

• Status: Active, not recruiting
• Trial end date: 2021-12-30
• Target enrollment: 0
• Participant gender: All

Summary

To evaluate the effect of early viral reactivation by latency reversing agents (LRA) and/or administration of potent broadly neutralizing antibodies (bNAb) on the size of the latent HIV-1 reservoir in treatment naïve HIV-1 patients initiating antiretroviral therapy (ART)

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

Details

• Lead Sponsor: Aarhus University Hospital
• Collaborators: Aalborg Universitetshospital; Aalborg University Hospital; Hammersmith Hospitals NHS Trust; Herning Hospital; Hvidovre University Hospital; Odense University Hospital; Rigshospitalet, Denmark; St Mary's Hospital, London; University Hospital of Cologne
• Treatments: Anti-Retroviral Agents; Antibodies; Antibodies, Blocking; Romidepsin

Criteria

Inclusion Criteria:

• Documented HIV-1 infection

• CD4+ T cell count >200/µL on last visit prior to study entry

• ART naïve

• Able to give informed consent

Exclusion Criteria:

• Any significant acute medical illness (not including primary HIV infection) in the past 8 weeks

• Any evidence of an active AIDS-defining opportunistic infection

• Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy

• The following laboratory values at screening, but the values can be repeated within the screening period, but test results must be available before baseline (day 0) and checked for eligibility:

• Hepatic transaminases (AST or ALT) ≥3 x upper limit of normal (ULN)

• Serum total bilirubin ≥3 ULN

• Estimated glomerular filtration rate (eGFR) ≤60 mL/min (based on serum creatinine or other appropriate validated markers)

• Platelet count ≤100 x10^9/L

• Absolute neutrophil count ≤1x10^9/L

• Serum potassium, magnesium, phosphorus outside ≥1.5 ULN/LLN

• Total calcium (corrected for serum albumin) or ionized calcium ≥1.5 ULN/LLN

• 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

• ECG at screening that shows QTc >450 ms when calculated using the Fridericia formula from either lead V3 or V4 [86]

• Use of:

• Warfarin or warfarin-derivatives

• HDACi

• An agent definitely or possibly associated with effects on QT intervals within 2 weeks of screening

• Drugs that induce or inhibit CYP3A4 or P-gp

• History of:

• Clinically significant cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for Torsades de pointes (e.g. heart failure)

• Malignancy or transplantation, including skin cancers or Kaposi sarcoma

• Diabetes mellitus

• Receipt of strong immunosuppressive or systemic chemotherapeutic agents within 28 days prior to study entry

• Known resistance to >2 classes of ART

• Known hypersensitivity to the components of romidepsin, 3BNC117 or their analogues

• Women who are pregnant or breastfeeding, or with a positive pregnancy test during screening or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method of non-estrogen containing contraceptions (according to the Danish Medicines Agency guidelines) to avoid pregnancy for the 3 week study period and 4 weeks after study treatment or until undetectable plasma HIV-1 RNA using standard assays

• Males or females who are unwilling or unable to use barrier contraception during sexual intercourse for the 3-week study period, and 4 weeks after study treatment or until undetectable plasma HIV-1 RNA using standard assays