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

Early Administration of Latency Reversing Therapy and Broadly Neutralizing Antibodies to Limit the Establishment of the HIV-1 Reservoir During Initiation of Antiretroviral Treatment - a Randomized Controlled Trial

Sponsors

Lead Sponsor: Aarhus University Hospital

Collaborator: Rigshospitalet, Denmark
Hvidovre University Hospital
Odense University Hospital
Aalborg University Hospital
Herning Hospital
Hammersmith Hospitals NHS Trust
St Mary's Hospital, London

Source University of Aarhus
Brief 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)

Detailed 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.

Overall Status Active, not recruiting
Start Date January 20, 2017
Completion Date June 30, 2021
Primary Completion Date March 20, 2021
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Plasma HIV RNA kinetics 3 months
Quantification of the size of the proviral HIV reservoir 1 year
Secondary Outcome
Measure Time Frame
Incidence of treatment emerging events (Safety and tolerability) 1 year
Quantification of the integrated HIV DNA 1 year
Quantification of the size of the replication-competent HIV reservoir 1 year
Immune reconstitution 1 year
Analytic treatment interruption (ATI) study 64 weeks
Enrollment 60
Condition
Intervention

Intervention Type: Drug

Intervention Name: Romidepsin

Description: 5mg/m2 romidepsin will be administered IV on days 10, 17, and 24 after initiating ART

Other Name: Istodax

Intervention Type: Drug

Intervention Name: 3BNC117

Description: 30 mg/kg 3BNC117 will be administered IV on day 7 and 21 after initiating ART

Other Name: Broadly neutralizing antibody

Intervention Type: Drug

Intervention Name: Antiretrovirals

Description: Combination antiretroviral therapy

Other Name: ART

Eligibility

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Ole S Søgaard, MD PhD Principal Investigator Aarhus University Hospital
Location
Facility:
Department of Infectious Diseases | Aalborg, Denmark
Dept. of Infectious Diseases, Aarhus University Hospital | Aarhus, 8200, Denmark
Department of Infectious Diseases | Hvidovre, Denmark
Department of Infectious Diseases | København, Denmark
Department of Infectious Diseases | Odense, Denmark
Guy's and St Thomas' | London, United Kingdom
Imperial College Healthcare NHS Trust | London, United Kingdom
Location Countries

Denmark

United Kingdom

Verification Date

August 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Number Of Arms 4
Arm Group

Label: antiretrovirals

Type: Placebo Comparator

Description: Standard of care

Label: antiretrovirals + romidepsin

Type: Active Comparator

Description: Standard of care + LRA

Label: antiretrovirals + 3BNC117

Type: Active Comparator

Description: Standard of care + bNAb

Label: antiretrovirals + romidepsin + 3BNC117

Type: Active Comparator

Description: Standard of care + LRA + bNAb

Acronym eCLEAR
Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Factorial Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov