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

September 3, 2021 updated by: Aarhus University Hospital

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

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)

Study Overview

Status

Active, not recruiting

Conditions

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 Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Aalborg, Denmark
        • Department of Infectious Diseases
      • Aarhus, Denmark, 8200
        • Dept. of Infectious Diseases, Aarhus University Hospital
      • Hvidovre, Denmark
        • Department of Infectious Diseases
      • København, Denmark
        • Department of Infectious Diseases
      • Odense, Denmark
        • Department of Infectious Diseases
      • London, United Kingdom
        • Imperial College Healthcare NHS Trust
      • London, United Kingdom
        • Guy's and St Thomas'

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: antiretrovirals
Standard of care
Combination antiretroviral therapy
Other Names:
  • ART
Active Comparator: antiretrovirals + romidepsin
Standard of care + LRA
Combination antiretroviral therapy
Other Names:
  • ART
5mg/m2 romidepsin will be administered IV on days 10, 17, and 24 after initiating ART
Other Names:
  • Istodax
Active Comparator: antiretrovirals + 3BNC117
Standard of care + bNAb
Combination antiretroviral therapy
Other Names:
  • ART
30 mg/kg 3BNC117 will be administered IV on day 7 and 21 after initiating ART
Other Names:
  • Broadly neutralizing antibody
Active Comparator: antiretrovirals + romidepsin + 3BNC117
Standard of care + LRA + bNAb
Combination antiretroviral therapy
Other Names:
  • ART
5mg/m2 romidepsin will be administered IV on days 10, 17, and 24 after initiating ART
Other Names:
  • Istodax
30 mg/kg 3BNC117 will be administered IV on day 7 and 21 after initiating ART
Other Names:
  • Broadly neutralizing antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma HIV RNA kinetics
Time Frame: 3 months
Time to undetectable (<20 c/mL)
3 months
Quantification of the size of the proviral HIV reservoir
Time Frame: 1 year
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
Time Frame: 12 weeks
Days from stopping ART to plasma HIV RNA >5,000 on two consecutive measurements
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of treatment emerging events (Safety and tolerability)
Time Frame: 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).
1 year
Quantification of the intact proviral DNA
Time Frame: 1 year
Intact HIV-1 DNA in CD4+ T cells (copies per million cells) as measured by dd-PCR.
1 year
Quantification of HIV mRNA and/or p24 positive cells
Time Frame: 30 days from study entry
Frequency of mRNA/p24 postive per 1 million CD4+ T cells by FISH-flow
30 days from study entry
Immune reconstitution
Time Frame: 1 year
Absolute CD4+ and CD8+ T cell count
1 year
Analytic treatment interruption (ATI) study
Time Frame: 64 weeks
Time to first plasma HIV RNA >5000 c/mL
64 weeks
Impact of pre-ART virus sensitivity to 3BNC117 on ATI outcomes
Time Frame: Baseline and at viral rebound
3BNC117 sensitivity determined by PhenoSense and/or HIV env sequencing
Baseline and at viral rebound
T cell mediated HIV specific immunity
Time Frame: First of 365 days
T cell immunity as determined by the HIV AIM assay
First of 365 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma cytokine and immune activation biomarker levels
Time Frame: 1 year
Soluble IL-6, sCD14, sCD163
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 20, 2017

Primary Completion (Actual)

August 20, 2021

Study Completion (Anticipated)

December 30, 2021

Study Registration Dates

First Submitted

January 20, 2017

First Submitted That Met QC Criteria

January 31, 2017

First Posted (Estimate)

February 2, 2017

Study Record Updates

Last Update Posted (Actual)

September 13, 2021

Last Update Submitted That Met QC Criteria

September 3, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

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 to be shared includes deidentified data points in published, peer-reviewed articles. Additional, related documents will also be available (study protocol, informed consent form). Data will become available following publication with no planned end date.

IPD Sharing 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.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Informed Consent Form (ICF)
  • Analytic Code

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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