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

Sponsor
Aarhus University Hospital (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03041012
Collaborator
Rigshospitalet, Denmark (Other), Hvidovre University Hospital (Other), Odense University Hospital (Other), Aalborg University Hospital (Other), Herning Hospital (Other), Hammersmith Hospitals NHS Trust (Other), St Mary's Hospital, London (Other)
60
Enrollment
7
Locations
4
Arms
59.3
Anticipated Duration (Months)
8.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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)

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
60 participants
Allocation:
Randomized
Intervention Model:
Factorial Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Jan 20, 2017
Actual Primary Completion Date :
Aug 20, 2021
Anticipated Study Completion Date :
Dec 30, 2021

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: antiretrovirals

Standard of care

Drug: Antiretrovirals
Combination antiretroviral therapy
Other Names:
  • ART

    		•
    Active Comparator: antiretrovirals + romidepsin

    Standard of care + LRA

    Drug: Romidepsin
    5mg/m2 romidepsin will be administered IV on days 10, 17, and 24 after initiating ART
    Other Names:
  • Istodax

    • Drug: Antiretrovirals
    Combination antiretroviral therapy
    Other Names:
  • ART

    		•
    Active Comparator: antiretrovirals + 3BNC117

    Standard of care + bNAb

    Drug: 3BNC117
    30 mg/kg 3BNC117 will be administered IV on day 7 and 21 after initiating ART
    Other Names:
  • Broadly neutralizing antibody

    • Drug: Antiretrovirals
    Combination antiretroviral therapy
    Other Names:
  • ART

    		•
    Active Comparator: antiretrovirals + romidepsin + 3BNC117

    Standard of care + LRA + bNAb

    Drug: Romidepsin
    5mg/m2 romidepsin will be administered IV on days 10, 17, and 24 after initiating ART
    Other Names:
  • Istodax

    • Drug: 3BNC117
    30 mg/kg 3BNC117 will be administered IV on day 7 and 21 after initiating ART
    Other Names:
  • Broadly neutralizing antibody

    • Drug: Antiretrovirals
    Combination antiretroviral therapy
    Other Names:
  • ART

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Plasma HIV RNA kinetics [3 months]

      Time to undetectable (<20 c/mL)

    2. Quantification of the size of the proviral HIV reservoir [1 year]

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

    3. Time to viral rebound during ATI [12 weeks]

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

    Secondary Outcome Measures

    1. Incidence of treatment emerging events (Safety and tolerability) [1 year]

      Frequence and severity of adverse events (AE), adverse reactions (AR), serious adverse events (SAE), serious adverse reactions (SAR) and suspected unexpected serious adverse reactions (SUSAR).

    2. Quantification of the intact proviral DNA [1 year]

      Intact HIV-1 DNA in CD4+ T cells (copies per million cells) as measured by dd-PCR.

    3. Quantification of HIV mRNA and/or p24 positive cells [30 days from study entry]

      Frequency of mRNA/p24 postive per 1 million CD4+ T cells by FISH-flow

    4. Immune reconstitution [1 year]

      Absolute CD4+ and CD8+ T cell count

    5. Analytic treatment interruption (ATI) study [64 weeks]

      Time to first plasma HIV RNA >5000 c/mL

    6. Impact of pre-ART virus sensitivity to 3BNC117 on ATI outcomes [Baseline and at viral rebound]

      3BNC117 sensitivity determined by PhenoSense and/or HIV env sequencing

    7. T cell mediated HIV specific immunity [First of 365 days]

      T cell immunity as determined by the HIV AIM assay

    Other Outcome Measures

    1. Plasma cytokine and immune activation biomarker levels [1 year]

      Soluble IL-6, sCD14, sCD163

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Department of Infectious Diseases Aalborg Denmark
    2 Dept. of Infectious Diseases, Aarhus University Hospital Aarhus Denmark 8200
    3 Department of Infectious Diseases Hvidovre Denmark
    4 Department of Infectious Diseases København Denmark
    5 Department of Infectious Diseases Odense Denmark
    6 Guy's and St Thomas' London United Kingdom
    7 Imperial College Healthcare NHS Trust London United Kingdom

    Sponsors and Collaborators

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

    Investigators

    • Principal Investigator: Ole S Søgaard, MD PhD, Aarhus University Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Aarhus University Hospital
    ClinicalTrials.gov Identifier:
    NCT03041012
    Other Study ID Numbers:
    • eCLEAR-001
    • 2015-002234-53
    First Posted:
    Feb 2, 2017
    Last Update Posted:
    Sep 13, 2021
    Last Verified:
    Apr 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Aarhus University Hospital
    HIV-1
    Latency Reversal Agent
    Immunotherapy
    Additional relevant MeSH terms:
    Anti-Retroviral Agents
    Romidepsin
    Antibodies, Blocking

    Study Results

    No Results Posted as of Sep 13, 2021