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

NCT03041012 | Completed Phase 2 DMC

• 2 other identifiers: eCLEAR-0012015-002234-53
• Study Type: interventional
• Target: 60
• Locations: 2 countries
• Sites: 7

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)

Conditions

Hiv

Keywords

HIV-1; Latency Reversal Agent; Immunotherapy

Outcome Measures

Primary Outcomes (3)

• Plasma HIV RNA kinetics

  Time to undetectable (\<20 c/mL)

  3 months

• Quantification of the size of the proviral HIV reservoir

  Copies of total HIV-1 DNA per 10⁶ CD4+ T cells as measured by digital droplet PCR

  1 year

• Time to viral rebound during ATI

  Days from stopping ART to plasma HIV RNA \>5,000 on two consecutive measurements

  12 weeks

Secondary Outcomes (7)

• Incidence of treatment emerging events (Safety and tolerability)

  1 year

• Quantification of the intact proviral DNA

  1 year

• Quantification of HIV mRNA and/or p24 positive cells

  30 days from study entry

• Immune reconstitution

  1 year

• Analytic treatment interruption (ATI) study

  64 weeks

Other Outcomes (1)

• Plasma cytokine and immune activation biomarker levels

  1 year

Study Arms (4)

antiretrovirals

PLACEBO COMPARATOR

Standard of care

Drug: Antiretrovirals

antiretrovirals + romidepsin

ACTIVE COMPARATOR

Standard of care + LRA

Drug: Romidepsin; Drug: Antiretrovirals

antiretrovirals + 3BNC117

ACTIVE COMPARATOR

Standard of care + bNAb

Drug: 3BNC117; Drug: Antiretrovirals

antiretrovirals + romidepsin + 3BNC117

ACTIVE COMPARATOR

Standard of care + LRA + bNAb

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

Interventions

Romidepsin DRUG

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

Also known as: Istodax

antiretrovirals + romidepsin; antiretrovirals + romidepsin + 3BNC117

3BNC117 DRUG

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

Also known as: Broadly neutralizing antibody

antiretrovirals + 3BNC117; antiretrovirals + romidepsin + 3BNC117

Antiretrovirals DRUG

Combination antiretroviral therapy

Also known as: ART

antiretrovirals; antiretrovirals + 3BNC117; antiretrovirals + romidepsin; antiretrovirals + romidepsin + 3BNC117

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented HIV-1 infection
• CD4+ T cell count \>200/µL on last visit prior to study entry
• ART naïve
• Able to give informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Aarhus University Hospital: lead
• Rigshospitalet, Denmark: collaborator
• Hvidovre University Hospital: collaborator
• Odense University Hospital: collaborator
• Aalborg University Hospital: collaborator
• Herning Hospital: collaborator
• Hammersmith Hospitals NHS Trust: collaborator
• St Mary's Hospital, London: collaborator

Study Sites (7)

Department of Infectious Diseases

Aalborg, Denmark

Location

Dept. of Infectious Diseases, Aarhus University Hospital

Aarhus, 8200, Denmark

Location

Department of Infectious Diseases

Copenhagen, Denmark

Location

Department of Infectious Diseases

Hvidovre, Denmark

Location

Department of Infectious Diseases

Odense, Denmark

Location

Guy's and St Thomas'

London, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, United Kingdom

Location

Related Publications (1)

• Gunst JD, Pahus MH, Rosas-Umbert M, Lu IN, Benfield T, Nielsen H, Johansen IS, Mohey R, Ostergaard L, Klastrup V, Khan M, Schleimann MH, Olesen R, Stovring H, Denton PW, Kinloch NN, Copertino DC, Ward AR, Alberto WDC, Nielsen SD, Puertas MC, Ramos V, Reeves JD, Petropoulos CJ, Martinez-Picado J, Brumme ZL, Jones RB, Fox J, Tolstrup M, Nussenzweig MC, Caskey M, Fidler S, Sogaard OS. Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1: a phase 1b/2a, randomized trial. Nat Med. 2022 Nov;28(11):2424-2435. doi: 10.1038/s41591-022-02023-7. Epub 2022 Oct 17.

  PMID: 36253609 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

romidepsin; 3BNC117 antibody; Broadly Neutralizing Antibodies; Anti-Retroviral Agents

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Neutralizing; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antiviral Agents; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Ole S Søgaard, MD PhD

  Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2017
• First Posted: February 2, 2017
• Study Start: January 20, 2017
• Primary Completion: August 20, 2021
• Study Completion: December 30, 2022
• Last Updated: April 18, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, ANALYTIC CODE
• Time Frame: Individual deidentified participant data (including data dictionaries) will be shared following the publication of the primary and secondary endpoints as outlined in this protocol. Data will become available following publication with no planned end date.
• Access Criteria: Access to the data sharing will be given to researchers who provide a methodologically sound proposal for any type of analysis and requires IRB/Ethics committee approval (if applicable). Proposal should be addressed to olesoega@rm.dk.

Locations

DK (5); GB (2)