<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/NCT04500418</url>
  </required_header>
  <id_info>
    <org_study_id>CVC for COVID-19</org_study_id>
    <secondary_id>2020-001493-29</secondary_id>
    <nct_id>NCT04500418</nct_id>
  </id_info>
  <brief_title>Charité Trial of Cenicriviroc (CVC) Treatment for COVID-19 Patients</brief_title>
  <official_title>Charité Trial of Cenicriviroc (CVC) Treatment for COVID-19 Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Charite University, Berlin, Germany</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Allergan</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Charite University, Berlin, Germany</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>
      The aim of this study is to test Cenicriviroc (CVC) as a means to reduce the severity of the&#xD;
      lung disease COVID-19 caused by an infection with SARS-CoV-2. The safety of CVC, when&#xD;
      administered to COVID-19 patients, will also be assessed. Furthermore, the clinical trial&#xD;
      aims to answer the question of whether patients with pre-existing conditions, who have an&#xD;
      increased risk of severe COVID-19 progression, benefit more and particularly from CVC. CVC is&#xD;
      an orally available dual inhibitor of the chemokine receptors CCR2 and CCR5, which is&#xD;
      expected to reduce (hyper-) inflammation in COVID-19.&#xD;
&#xD;
      The main goal of the study is to determine whether CVC helps increase the number of patients&#xD;
      who are symptom-free and not hospitalized after 14 days compared to a placebo. Approximately&#xD;
      66.7% of the patients enrolled in the study will receive CVC and 33.3% will get an optically&#xD;
      identical pill (placebo).&#xD;
&#xD;
      Subjects will be assessed daily while hospitalized. Discharged patients will be asked to&#xD;
      attend study visits at Days 8, 15, 22, and 29 and 85. All subjects will undergo a series of&#xD;
      clinical, safety, and laboratory assessments. Blood samples and oropharyngeal (OP) swabs will&#xD;
      be obtained on Day 1; 3, 5 (while hospitalized); and Day 8, 15 and 29 (if able to return to&#xD;
      clinic or still hospitalized). The presence of anti-SARS-CoV-2 antibodies will be determined&#xD;
      on Days 29 and 85.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Despite multiple efforts, no further patient could be enrolled since 03/05/2021. A continuation&#xD;
    of the study is therefore no longer justified&#xD;
  </why_stopped>
  <start_date type="Actual">August 25, 2020</start_date>
  <completion_date type="Actual">July 27, 2021</completion_date>
  <primary_completion_date type="Actual">July 27, 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>Parallel Assignment</intervention_model>
    <intervention_model_description>A monocentric, randomized, double-blind, placebo-controlled trial.&#xD;
Randomization will be stratified by:&#xD;
Presence of baseline score of &quot;3&quot; on 7-point ordinal scale versus presence of baseline score of &quot;4&quot; or &quot;5&quot; on seven-point ordinal scale&#xD;
Presence of one or more of the following comorbidities: Diabetes mellitus, Obesity (BMI &gt;30kg/m2), COPD or Asthma, Heart failure (NYHA Class I or II)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Subject´s Responder status (score on the 7-point ordinal scale on Day 15)</measure>
    <time_frame>14 days after enrollment (Day 15)</time_frame>
    <description>The Primary Endpoint will be the subject's responder status defined by achieving a score of &quot;1&quot; or &quot;2&quot; (discharged from hospital e.g.) on Day 15 on the following 7-point scale:&#xD;
Not hospitalized, no limitations on activities;&#xD;
Not hospitalized, limitation on activities;&#xD;
Hospitalized, not requiring supplemental oxygen;&#xD;
Hospitalized, requiring supplemental oxygen;&#xD;
Hospitalized, on non-invasive ventilation or high-flow oxygen devices;&#xD;
Hospitalized, on invasive mechanical ventilation or ECMO (Extracorporeal membrane oxygenation);&#xD;
Death.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluation of change in clinical condition based on the 7-point ordinal scale</measure>
    <time_frame>day of enrollment and 15 days after enrollment</time_frame>
    <description>7-point ordinal scale to be assessed on Day 15 (and Day 1 for baseline comparison), analyses of&#xD;
ordinal change of 2 or more, compared with baseline&#xD;
ordinal change of 1 or more, compared with baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of change in clinical condition based on the 7-point ordinal scale and Responder Status</measure>
    <time_frame>day of enrollment, 8 days, 22 days and 29 days after enrollment</time_frame>
    <description>7-point ordinal scale assessed on: Days 8, 22, 29 (and Day 1 for baseline comparison), analyses of:&#xD;
Responder status (achieving a score of a &quot;1&quot; or a &quot;2&quot;)&#xD;
ordinal change of 2 or more, compared with baseline&#xD;
ordinal change of 1 or more, compared with baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital resource utilization comparison</measure>
    <time_frame>29 days after enrollment, 85 days after enrollment</time_frame>
    <description>Analysis of:&#xD;
Length of time spent in the ICU (days)&#xD;
Length of time spent in the hospital (days)&#xD;
Days alive and out of hospital through Day 29&#xD;
Days free of endotracheal tube-based ventilation through Day 29</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Covid19</condition>
  <arm_group>
    <arm_group_label>Cenicriviroc (CVC)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Approximately 122 patients. Day 1: CVC 450 mg (300 mg AM; 150 mg PM; if patients receive their first dose on Day 1 past 2 PM, then their evening dose will be 300 mg and their next dose will be the following AM.) Days 2-28: CVC BID 150 mg (AM/PM). Every dose should be taken with food (within 30 min).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Approximately 61 patients. A matching placebo will be given to the patients in the Placebo group at an equal volume and at the same schedule.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cenicriviroc (CVC)</intervention_name>
    <description>Treatment with Cenicriviroc tablets of 150mg. (450g/300g on day 1 and 300mg/d on days 2-28).</description>
    <arm_group_label>Cenicriviroc (CVC)</arm_group_label>
    <other_name>Cenicriviroc Mesylate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Optically identical pills without CVC.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject provides written informed consent prior to initiation of any study procedures.&#xD;
             Understands and agrees to comply with planned study procedures.&#xD;
&#xD;
          -  Male or non-pregnant female adult ≥18 years of age at time of enrolment.&#xD;
&#xD;
          -  Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR and fulfils the&#xD;
             case criteria of COVID-19 (One or more of the following must be met in lieu of a&#xD;
             positive PCR test: fever [defined as a temperature ≥ 100.0°F / 37.8°C documented&#xD;
             within 24 hr. of randomization] , absolute and relative lymphopenia and leukopenia,&#xD;
             new typical infiltrates in x-ray of the chest or chest CT scan [only if obtained for&#xD;
             clinical reasons; not required by study], no improvement on antibiotics).&#xD;
&#xD;
          -  Scoring a &quot;3&quot; or &quot;4&quot; (or &quot;5&quot;, at the Investigator's discretion) on the 7-Point Ordinal&#xD;
             Scale (see Outcome Measures) at enrolment. Note, if scoring a &quot;2&quot; at screening,&#xD;
             inclusion will be met if the patient is in the process of being hospitalized or&#xD;
             admitted to an inpatient setting. Such a patient would be assigned a &quot;3&quot; at enrolment&#xD;
             for Baseline assessment purposes.&#xD;
&#xD;
          -  No participation in other clinical trials according to the German Medicines Act (AMG)&#xD;
             (3 months before) at the time of this trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  ALT/AST &gt; 5 times the upper limit of normal.&#xD;
&#xD;
          -  Patients with severe hepatic impairment (defined as liver cirrhosis Child stage B or&#xD;
             C)&#xD;
&#xD;
          -  Stage 4 chronic kidney disease or requiring dialysis (i.e. eGFR &lt; 30 ml/min)&#xD;
&#xD;
          -  Advanced cardiac (eg, severe heart failure [NYHA III-IV]) or pulmonary diseases which,&#xD;
             in the Investigator's judgment, would not make participation appropriate.&#xD;
&#xD;
          -  Pregnancy or breast feeding.&#xD;
&#xD;
          -  Anticipated transfer to another hospital which is not a study site within 72 hours.&#xD;
&#xD;
          -  Known allergy or hypersensitivity to CVC or its components.&#xD;
&#xD;
          -  Use of medications that are contraindicated with CVC and that could not be replaced or&#xD;
             stopped during the trial period&#xD;
&#xD;
          -  Administration of specified drugs which interfere with the metabolism of CVC.&#xD;
&#xD;
          -  Patients immediately or imminently requiring mechanical ventilation.&#xD;
&#xD;
          -  Patients unwilling to consent to saving and propagation of pseudonymised medical data&#xD;
             for study reasons.&#xD;
&#xD;
          -  Subjects who are legally detained in an official institution.&#xD;
&#xD;
          -  Subjects that are unsuitable to understand or to comply with the study requirements in&#xD;
             the opinion of the investigator.&#xD;
&#xD;
          -  Subjects who may be dependent on the sponsor, the investigator or the trial sites.&#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>Frank Tacke, Prof. Dr.med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Charité University, Berlin, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical Department of Hepatology and Gastroenterology, Charité University Medicine, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM)</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>August 4, 2020</study_first_submitted>
  <study_first_submitted_qc>August 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>March 14, 2022</last_update_submitted>
  <last_update_submitted_qc>March 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Charite University, Berlin, Germany</investigator_affiliation>
    <investigator_full_name>Prof. Dr. med. Frank Tacke</investigator_full_name>
    <investigator_title>Prof. Dr. med., PhD, MHBA</investigator_title>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>Cenicriviroc</keyword>
  <keyword>CVC</keyword>
  <keyword>SARS-CoV-2</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cenicriviroc</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Undecided at this moment. (08/2020)</ipd_description>
  </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/NCT04500418
org study id: CVC for COVID-19
secondary id: 2020-001493-29
nct id: NCT04500418
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The aim of this study is to test Cenicriviroc (CVC) as a means to reduce the severity of the
      lung disease COVID-19 caused by an infection with SARS-CoV-2. The safety of CVC, when
      administered to COVID-19 patients, will also be assessed. Furthermore, the clinical trial
      aims to answer the question of whether patients with pre-existing conditions, who have an
      increased risk of severe COVID-19 progression, benefit more and particularly from CVC. CVC is
      an orally available dual inhibitor of the chemokine receptors CCR2 and CCR5, which is
      expected to reduce (hyper-) inflammation in COVID-19.

      The main goal of the study is to determine whether CVC helps increase the number of patients
      who are symptom-free and not hospitalized after 14 days compared to a placebo. Approximately
      66.7% of the patients enrolled in the study will receive CVC and 33.3% will get an optically
      identical pill (placebo).

      Subjects will be assessed daily while hospitalized. Discharged patients will be asked to
      attend study visits at Days 8, 15, 22, and 29 and 85. All subjects will undergo a series of
      clinical, safety, and laboratory assessments. Blood samples and oropharyngeal (OP) swabs will
      be obtained on Day 1; 3, 5 (while hospitalized); and Day 8, 15 and 29 (if able to return to
      clinic or still hospitalized). The presence of anti-SARS-CoV-2 antibodies will be determined
      on Days 29 and 85.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: A monocentric, randomized, double-blind, placebo-controlled trial.
Randomization will be stratified by:
Presence of baseline score of "3" on 7-point ordinal scale versus presence of baseline score of "4" or "5" on seven-point ordinal scale
Presence of one or more of the following comorbidities: Diabetes mellitus, Obesity (BMI >30kg/m2), COPD or Asthma, Heart failure (NYHA Class I or II)
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Subject´s Responder status (score on the 7-point ordinal scale on Day 15)
time frame: 14 days after enrollment (Day 15)
description: The Primary Endpoint will be the subject's responder status defined by achieving a score of "1" or "2" (discharged from hospital e.g.) on Day 15 on the following 7-point scale:
Not hospitalized, no limitations on activities;
Not hospitalized, limitation on activities;
Hospitalized, not requiring supplemental oxygen;
Hospitalized, requiring supplemental oxygen;
Hospitalized, on non-invasive ventilation or high-flow oxygen devices;
Hospitalized, on invasive mechanical ventilation or ECMO (Extracorporeal membrane oxygenation);
Death.
measure: Evaluation of change in clinical condition based on the 7-point ordinal scale
time frame: day of enrollment and 15 days after enrollment
description: 7-point ordinal scale to be assessed on Day 15 (and Day 1 for baseline comparison), analyses of
ordinal change of 2 or more, compared with baseline
ordinal change of 1 or more, compared with baseline
measure: Evaluation of change in clinical condition based on the 7-point ordinal scale and Responder Status
time frame: day of enrollment, 8 days, 22 days and 29 days after enrollment
description: 7-point ordinal scale assessed on: Days 8, 22, 29 (and Day 1 for baseline comparison), analyses of:
Responder status (achieving a score of a "1" or a "2")
ordinal change of 2 or more, compared with baseline
ordinal change of 1 or more, compared with baseline
measure: Hospital resource utilization comparison
time frame: 29 days after enrollment, 85 days after enrollment
description: Analysis of:
Length of time spent in the ICU (days)
Length of time spent in the hospital (days)
Days alive and out of hospital through Day 29
Days free of endotracheal tube-based ventilation through Day 29
arm group label: Cenicriviroc (CVC)
arm group type: Active Comparator
description: Approximately 122 patients. Day 1: CVC 450 mg (300 mg AM; 150 mg PM; if patients receive their first dose on Day 1 past 2 PM, then their evening dose will be 300 mg and their next dose will be the following AM.) Days 2-28: CVC BID 150 mg (AM/PM). Every dose should be taken with food (within 30 min).
arm group label: Placebo
arm group type: Placebo Comparator
description: Approximately 61 patients. A matching placebo will be given to the patients in the Placebo group at an equal volume and at the same schedule.
intervention type: Drug
intervention name: Cenicriviroc (CVC)
description: Treatment with Cenicriviroc tablets of 150mg. (450g/300g on day 1 and 300mg/d on days 2-28).
arm group label: Cenicriviroc (CVC)
other name: Cenicriviroc Mesylate
intervention type: Drug
intervention name: Placebo
description: Optically identical pills without CVC.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Frank Tacke, Prof. Dr.med.
role: Principal Investigator
affiliation: Charité University, Berlin, Germany
facility: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: Charite University, Berlin, Germany
investigator full name: Prof. Dr. med. Frank Tacke
investigator title: Prof. Dr. med., PhD, MHBA
mesh term: COVID-19
mesh term: Cenicriviroc
sharing ipd: Undecided
ipd description: Undecided at this moment. (08/2020)