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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03041012
Recruitment Status : Active, not recruiting
First Posted : February 2, 2017
Last Update Posted : April 28, 2021
Sponsor:
Collaborators:
Rigshospitalet, Denmark
Hvidovre University Hospital
Odense University Hospital
Aalborg University Hospital
Herning Hospital
Hammersmith Hospitals NHS Trust
St Mary's Hospital, London
Information provided by (Responsible Party):
University of Aarhus ( Aarhus University Hospital )

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
Hiv Drug: Romidepsin Drug: 3BNC117 Drug: Antiretrovirals 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.

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Study Type : Interventional  (Clinical Trial)
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 : January 20, 2017
Estimated Primary Completion Date : August 20, 2021
Estimated Study Completion Date : December 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Romidepsin

Arm Intervention/treatment
Placebo Comparator: antiretrovirals
Standard of care
Drug: Antiretrovirals
Combination antiretroviral therapy
Other Name: 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 Name: Istodax

Drug: Antiretrovirals
Combination antiretroviral therapy
Other Name: 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 Name: Broadly neutralizing antibody

Drug: Antiretrovirals
Combination antiretroviral therapy
Other Name: 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 Name: Istodax

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

Drug: Antiretrovirals
Combination antiretroviral therapy
Other Name: ART




Primary Outcome Measures :
  1. Plasma HIV RNA kinetics [ Time Frame: 3 months ]
    Time to undetectable (<20 c/mL)

  2. 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


Secondary Outcome Measures :
  1. 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).

  2. Quantification of the integrated HIV DNA [ Time Frame: 1 year ]
    Integrated HIV-1 DNA in CD4+ T cells (copies per million cells) as measured by alu-PCR.

  3. Quantification of the size of the replication-competent HIV reservoir [ Time Frame: 1 year ]
    The frequency of CD4+ T cells latently infected with replication competent HIV as measured by infectious units per million (IUPM) CD4+ T cells in a viral outgrowth assay

  4. Immune reconstitution [ Time Frame: 1 year ]
    Absolute CD4+ and CD8+ T cell count

  5. Analytic treatment interruption (ATI) study [ Time Frame: 64 weeks ]
    Time to plasma HIV RNA >5000 c/mL on two consecutive measurements


Other Outcome Measures:
  1. Plasma cytokine and immune activation biomarker levels [ Time Frame: 1 year ]
    Soluble IL-6, sCD14, sCD163



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03041012


Locations
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Denmark
Department of Infectious Diseases
Aalborg, Denmark
Dept. of Infectious Diseases, Aarhus University Hospital
Aarhus, Denmark, 8200
Department of Infectious Diseases
Hvidovre, Denmark
Department of Infectious Diseases
København, Denmark
Department of Infectious Diseases
Odense, Denmark
United Kingdom
Guy's and St Thomas'
London, United Kingdom
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
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Principal Investigator: Ole S Søgaard, MD PhD Aarhus University Hospital
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Responsible Party: Aarhus University Hospital
ClinicalTrials.gov Identifier: NCT03041012    
Other Study ID Numbers: eCLEAR-001
2015-002234-53 ( EudraCT Number )
First Posted: February 2, 2017    Key Record Dates
Last Update Posted: April 28, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Informed Consent Form (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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Aarhus ( Aarhus University Hospital ):
HIV-1
Latency Reversal Agent
Immunotherapy
Additional relevant MeSH terms:
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Anti-Retroviral Agents
Romidepsin
Antiviral Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents