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

April 15, 2025 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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Denmark
      • 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
  • United Kingdom
      • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: antiretrovirals
Standard of care
Drug: Antiretrovirals
Combination antiretroviral therapy
Other Names:
  • ART
Active Comparator: antiretrovirals + romidepsin
Standard of care + LRA
Drug: Antiretrovirals
Combination antiretroviral therapy
Other Names:
  • ART
Drug: Romidepsin
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
Drug: Antiretrovirals
Combination antiretroviral therapy
Other Names:
  • ART
Drug: 3BNC117
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
Drug: Antiretrovirals
Combination antiretroviral therapy
Other Names:
  • ART
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
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.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Aarhus University Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Odense University Hospital
Rigshospitalet, Denmark
Hvidovre University Hospital
Herning Hospital
Aalborg University Hospital
St Mary's Hospital, London
Hammersmith Hospitals NHS Trust

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ole S Søgaard, MD PhD, Aarhus University Hospital

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 20, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 20, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 20, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 31, 2017

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 2, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 18, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 15, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • eCLEAR-001
  • 2015-002234-53 (EudraCT Number)

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
  • 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

product manufactured in and exported from the U.S.

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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