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

Aarhus University Hospital

Status and phase: Completed; Phase 2

Conditions: Hiv

Treatments: Drug: Antiretrovirals; Drug: 3BNC117; Drug: Romidepsin

Study type: Interventional

Funder types: Other

Identifiers

NCT03041012

eCLEAR-001

2015-002234-53 (EudraCT Number)

Details and patient eligibility

About

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)

Full description

The study will be conducted among ART naïve HIV-1-infected patients.

Subjects will continue ART while receiving LRA romidepsin and/or bNAb 3BNC117.

Enrollment: 60 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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60 participants in 4 patient groups, including a placebo group

antiretrovirals

Placebo Comparator group

Description:

Standard of care

Treatment:

Drug: Antiretrovirals

antiretrovirals + romidepsin

Active Comparator group

Description:

Standard of care + LRA

Treatment:

Drug: Romidepsin

Drug: Antiretrovirals

antiretrovirals + 3BNC117

Active Comparator group

Description:

Standard of care + bNAb

Treatment:

Drug: 3BNC117

Drug: Antiretrovirals

antiretrovirals + romidepsin + 3BNC117

Active Comparator group

Description:

Standard of care + LRA + bNAb

Treatment:

Drug: Romidepsin

Drug: 3BNC117

Drug: Antiretrovirals