<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03041012</url>
  </required_header>
  <id_info>
    <org_study_id>eCLEAR-001</org_study_id>
    <secondary_id>2015-002234-53</secondary_id>
    <nct_id>NCT03041012</nct_id>
  </id_info>
  <brief_title>Early Administration of Romidepsin and 3BNC117 in Treatment-naïve HIV Patients Starting ART</brief_title>
  <acronym>eCLEAR</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aarhus University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Rigshospitalet, Denmark</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hvidovre University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Odense University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Aalborg University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Herning Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hammersmith Hospitals NHS Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>St Mary's Hospital, London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Aarhus</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the effect of early viral reactivation by latency reversing agents (LRA) and/or&#xD;
      administration of potent broadly neutralizing antibodies (bNAb) on the size of the latent&#xD;
      HIV-1 reservoir in treatment naïve HIV-1 patients initiating antiretroviral therapy (ART)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will be conducted among ART naïve HIV-1-infected patients.&#xD;
&#xD;
      Subjects will continue ART while receiving LRA romidepsin and/or bNAb 3BNC117.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 20, 2017</start_date>
  <completion_date type="Anticipated">December 30, 2021</completion_date>
  <primary_completion_date type="Actual">August 20, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Plasma HIV RNA kinetics</measure>
    <time_frame>3 months</time_frame>
    <description>Time to undetectable (&lt;20 c/mL)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Quantification of the size of the proviral HIV reservoir</measure>
    <time_frame>1 year</time_frame>
    <description>Copies of total HIV-1 DNA per 10⁶ CD4+ T cells as measured by digital droplet PCR</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to viral rebound during ATI</measure>
    <time_frame>12 weeks</time_frame>
    <description>Days from stopping ART to plasma HIV RNA &gt;5,000 on two consecutive measurements</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment emerging events (Safety and tolerability)</measure>
    <time_frame>1 year</time_frame>
    <description>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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantification of the intact proviral DNA</measure>
    <time_frame>1 year</time_frame>
    <description>Intact HIV-1 DNA in CD4+ T cells (copies per million cells) as measured by dd-PCR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantification of HIV mRNA and/or p24 positive cells</measure>
    <time_frame>30 days from study entry</time_frame>
    <description>Frequency of mRNA/p24 postive per 1 million CD4+ T cells by FISH-flow</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune reconstitution</measure>
    <time_frame>1 year</time_frame>
    <description>Absolute CD4+ and CD8+ T cell count</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analytic treatment interruption (ATI) study</measure>
    <time_frame>64 weeks</time_frame>
    <description>Time to first plasma HIV RNA &gt;5000 c/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact of pre-ART virus sensitivity to 3BNC117 on ATI outcomes</measure>
    <time_frame>Baseline and at viral rebound</time_frame>
    <description>3BNC117 sensitivity determined by PhenoSense and/or HIV env sequencing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T cell mediated HIV specific immunity</measure>
    <time_frame>First of 365 days</time_frame>
    <description>T cell immunity as determined by the HIV AIM assay</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Plasma cytokine and immune activation biomarker levels</measure>
    <time_frame>1 year</time_frame>
    <description>Soluble IL-6, sCD14, sCD163</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Hiv</condition>
  <arm_group>
    <arm_group_label>antiretrovirals</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Standard of care</description>
  </arm_group>
  <arm_group>
    <arm_group_label>antiretrovirals + romidepsin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard of care + LRA</description>
  </arm_group>
  <arm_group>
    <arm_group_label>antiretrovirals + 3BNC117</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard of care + bNAb</description>
  </arm_group>
  <arm_group>
    <arm_group_label>antiretrovirals + romidepsin + 3BNC117</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard of care + LRA + bNAb</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Romidepsin</intervention_name>
    <description>5mg/m2 romidepsin will be administered IV on days 10, 17, and 24 after initiating ART</description>
    <arm_group_label>antiretrovirals + romidepsin</arm_group_label>
    <arm_group_label>antiretrovirals + romidepsin + 3BNC117</arm_group_label>
    <other_name>Istodax</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>3BNC117</intervention_name>
    <description>30 mg/kg 3BNC117 will be administered IV on day 7 and 21 after initiating ART</description>
    <arm_group_label>antiretrovirals + 3BNC117</arm_group_label>
    <arm_group_label>antiretrovirals + romidepsin + 3BNC117</arm_group_label>
    <other_name>Broadly neutralizing antibody</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Antiretrovirals</intervention_name>
    <description>Combination antiretroviral therapy</description>
    <arm_group_label>antiretrovirals</arm_group_label>
    <arm_group_label>antiretrovirals + 3BNC117</arm_group_label>
    <arm_group_label>antiretrovirals + romidepsin</arm_group_label>
    <arm_group_label>antiretrovirals + romidepsin + 3BNC117</arm_group_label>
    <other_name>ART</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Documented HIV-1 infection&#xD;
&#xD;
          -  CD4+ T cell count &gt;200/µL on last visit prior to study entry&#xD;
&#xD;
          -  ART naïve&#xD;
&#xD;
          -  Able to give informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any significant acute medical illness (not including primary HIV infection) in the&#xD;
             past 8 weeks&#xD;
&#xD;
          -  Any evidence of an active AIDS-defining opportunistic infection&#xD;
&#xD;
          -  Active alcohol or substance use that, in the Investigator's opinion, will prevent&#xD;
             adequate compliance with study therapy&#xD;
&#xD;
          -  The following laboratory values at screening, but the values can be repeated within&#xD;
             the screening period, but test results must be available before baseline (day 0) and&#xD;
             checked for eligibility:&#xD;
&#xD;
               -  Hepatic transaminases (AST or ALT) ≥3 x upper limit of normal (ULN)&#xD;
&#xD;
               -  Serum total bilirubin ≥3 ULN&#xD;
&#xD;
               -  Estimated glomerular filtration rate (eGFR) ≤60 mL/min (based on serum creatinine&#xD;
                  or other appropriate validated markers)&#xD;
&#xD;
               -  Platelet count ≤100 x10^9/L&#xD;
&#xD;
               -  Absolute neutrophil count ≤1x10^9/L&#xD;
&#xD;
               -  Serum potassium, magnesium, phosphorus outside ≥1.5 ULN/LLN&#xD;
&#xD;
               -  Total calcium (corrected for serum albumin) or ionized calcium ≥1.5 ULN/LLN&#xD;
&#xD;
               -  Hepatitis B or C infection as indicated by the presence of hepatitis B surface&#xD;
                  antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood&#xD;
&#xD;
          -  ECG at screening that shows QTc &gt;450 ms when calculated using the Fridericia formula&#xD;
             from either lead V3 or V4 [86]&#xD;
&#xD;
          -  Use of:&#xD;
&#xD;
               -  Warfarin or warfarin-derivatives&#xD;
&#xD;
               -  HDACi&#xD;
&#xD;
               -  An agent definitely or possibly associated with effects on QT intervals within 2&#xD;
                  weeks of screening&#xD;
&#xD;
               -  Drugs that induce or inhibit CYP3A4 or P-gp&#xD;
&#xD;
          -  History of:&#xD;
&#xD;
               -  Clinically significant cardiac disease, symptomatic or asymptomatic arrhythmias,&#xD;
                  syncopal episodes, or additional risk factors for Torsades de pointes (e.g. heart&#xD;
                  failure)&#xD;
&#xD;
               -  Malignancy or transplantation, including skin cancers or Kaposi sarcoma&#xD;
&#xD;
               -  Diabetes mellitus&#xD;
&#xD;
          -  Receipt of strong immunosuppressive or systemic chemotherapeutic agents within 28 days&#xD;
             prior to study entry&#xD;
&#xD;
          -  Known resistance to &gt;2 classes of ART&#xD;
&#xD;
          -  Known hypersensitivity to the components of romidepsin, 3BNC117 or their analogues&#xD;
&#xD;
          -  Women who are pregnant or breastfeeding, or with a positive pregnancy test during&#xD;
             screening or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to&#xD;
             use an acceptable method of non-estrogen containing contraceptions (according to the&#xD;
             Danish Medicines Agency guidelines) to avoid pregnancy for the 3 week study period and&#xD;
             4 weeks after study treatment or until undetectable plasma HIV-1 RNA using standard&#xD;
             assays&#xD;
&#xD;
          -  Males or females who are unwilling or unable to use barrier contraception during&#xD;
             sexual intercourse for the 3-week study period, and 4 weeks after study treatment or&#xD;
             until undetectable plasma HIV-1 RNA using standard assays&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ole S Søgaard, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Aarhus University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Infectious Diseases</name>
      <address>
        <city>Aalborg</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dept. of Infectious Diseases, Aarhus University Hospital</name>
      <address>
        <city>Aarhus</city>
        <zip>8200</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Infectious Diseases</name>
      <address>
        <city>Hvidovre</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Infectious Diseases</name>
      <address>
        <city>København</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Infectious Diseases</name>
      <address>
        <city>Odense</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guy's and St Thomas'</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imperial College Healthcare NHS Trust</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>January 20, 2017</study_first_submitted>
  <study_first_submitted_qc>January 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 2, 2017</study_first_posted>
  <last_update_submitted>September 3, 2021</last_update_submitted>
  <last_update_submitted_qc>September 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HIV-1</keyword>
  <keyword>Latency Reversal Agent</keyword>
  <keyword>Immunotherapy</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Retroviral Agents</mesh_term>
    <mesh_term>Romidepsin</mesh_term>
    <mesh_term>Antibodies, Blocking</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_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_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_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_time_frame>
    <ipd_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_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03041012
org study id: eCLEAR-001
secondary id: 2015-002234-53
nct id: NCT03041012
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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)
The study will be conducted among ART naïve HIV-1-infected patients.

      Subjects will continue ART while receiving LRA romidepsin and/or bNAb 3BNC117.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Plasma HIV RNA kinetics
time frame: 3 months
description: Time to undetectable (<20 c/mL)
measure: Quantification of the size of the proviral HIV reservoir
time frame: 1 year
description: Copies of total HIV-1 DNA per 10⁶ CD4+ T cells as measured by digital droplet PCR
measure: Time to viral rebound during ATI
time frame: 12 weeks
description: Days from stopping ART to plasma HIV RNA >5,000 on two consecutive measurements
measure: Incidence of treatment emerging events (Safety and tolerability)
time frame: 1 year
description: 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).
measure: Quantification of the intact proviral DNA
time frame: 1 year
description: Intact HIV-1 DNA in CD4+ T cells (copies per million cells) as measured by dd-PCR.
measure: Quantification of HIV mRNA and/or p24 positive cells
time frame: 30 days from study entry
description: Frequency of mRNA/p24 postive per 1 million CD4+ T cells by FISH-flow
measure: Immune reconstitution
time frame: 1 year
description: Absolute CD4+ and CD8+ T cell count
measure: Analytic treatment interruption (ATI) study
time frame: 64 weeks
description: Time to first plasma HIV RNA >5000 c/mL
measure: Impact of pre-ART virus sensitivity to 3BNC117 on ATI outcomes
time frame: Baseline and at viral rebound
description: 3BNC117 sensitivity determined by PhenoSense and/or HIV env sequencing
measure: T cell mediated HIV specific immunity
time frame: First of 365 days
description: T cell immunity as determined by the HIV AIM assay
measure: Plasma cytokine and immune activation biomarker levels
time frame: 1 year
description: Soluble IL-6, sCD14, sCD163
arm group label: antiretrovirals
arm group type: Placebo Comparator
description: Standard of care
arm group label: antiretrovirals + romidepsin
arm group type: Active Comparator
description: Standard of care + LRA
arm group label: antiretrovirals + 3BNC117
arm group type: Active Comparator
description: Standard of care + bNAb
arm group label: antiretrovirals + romidepsin + 3BNC117
arm group type: Active Comparator
description: Standard of care + LRA + bNAb
intervention type: Drug
intervention name: Romidepsin
description: 5mg/m2 romidepsin will be administered IV on days 10, 17, and 24 after initiating ART
arm group label: antiretrovirals + romidepsin
arm group label: antiretrovirals + romidepsin + 3BNC117
other name: Istodax
intervention type: Drug
intervention name: 3BNC117
description: 30 mg/kg 3BNC117 will be administered IV on day 7 and 21 after initiating ART
arm group label: antiretrovirals + 3BNC117
arm group label: antiretrovirals + romidepsin + 3BNC117
other name: Broadly neutralizing antibody
intervention type: Drug
intervention name: Antiretrovirals
description: Combination antiretroviral therapy
arm group label: antiretrovirals
arm group label: antiretrovirals + 3BNC117
arm group label: antiretrovirals + romidepsin
arm group label: antiretrovirals + romidepsin + 3BNC117
other name: ART
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ole S Søgaard, MD PhD
role: Principal Investigator
affiliation: Aarhus University Hospital
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Denmark
country: United Kingdom
responsible party type: Sponsor
mesh term: Anti-Retroviral Agents
mesh term: Romidepsin
mesh term: Antibodies, Blocking
sharing ipd: Yes
ipd 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 info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd info type: Analytic Code
ipd 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 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.