<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/NCT04435522</url>
  </required_header>
  <id_info>
    <org_study_id>1611471-1</org_study_id>
    <nct_id>NCT04435522</nct_id>
  </id_info>
  <brief_title>Maraviroc in Patients With Moderate and Severe COVID-19</brief_title>
  <official_title>Open-Label Study of Maraviroc in Hospitalized Individuals Diagnosed With SARS-CoV-2</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rhode Island Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rhode Island Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Maraviroc, a C-C Chemokine Receptor 5 (CCR5) antagonist, is well-tolerated without&#xD;
      significant side effects in its current use in patients with HIV. CCR5 antagonism prior to&#xD;
      the 'second wave' of inflammatory mediator expression in SARS-CoV-2 may reverse lymphoid&#xD;
      depletion and may alter cell trafficking of inflammatory cells, both increasing viral control&#xD;
      capacity and dampening damage to lung tissue, respectively. This study seeks to establish&#xD;
      whether one week of treatment with Maraviroc, used at its approved dosage for HIV, is safe&#xD;
      and tolerable in patients with SARS-CoV-2.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2020</start_date>
  <completion_date type="Actual">December 31, 2020</completion_date>
  <primary_completion_date type="Actual">December 31, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of Completion</measure>
    <time_frame>7 days</time_frame>
    <description>Rate of subjects who complete the 7-day course of Maraviroc without discontinuation for serious adverse event or death.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical improvement at Day 7</measure>
    <time_frame>7 days</time_frame>
    <description>Percent of patients at Day 7 from enrollment achieving reduction of two points on a seven-category ordinal scale (defined below).&#xD;
Ordinal scale: 1, not hospitalized with resumption of normal activities; 2, not hospitalized, but unable to resume normal activities OR hospitalized pending disposition, not requiring COVID-related care; 3, hospitalized, not requiring supplemental oxygen; 4, hospitalized, requiring supplemental oxygen; 5, hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; 6, hospitalized, requiring ECMO, invasive mechanical ventilation, or both; and, 7, death.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Chitinase 3-like 1(Chi3l1) (ng/mL)</measure>
    <time_frame>7 days</time_frame>
    <description>Measurement of Chi3l1 before, during and at completion of therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Interleukin-6 (IL-6) (pg/mL)</measure>
    <time_frame>7 Days</time_frame>
    <description>Measurement of IL-6 before, during and at completion of therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in CCL5 (RANTES) (ng/mL)</measure>
    <time_frame>7 Days</time_frame>
    <description>Measurement of CCL5 before, during and at completion of therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>28 days</time_frame>
    <description>7-, 14- and 28-day all-cause-mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Discharge</measure>
    <time_frame>28 days</time_frame>
    <description>Time to improvement to Score of 2 or less (Days)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days on mechanical ventilation</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>COVID</condition>
  <arm_group>
    <arm_group_label>Maraviroc Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Maraviroc 300 mg Twice Daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Maraviroc</intervention_name>
    <description>Maraviroc will be administered for seven days. Biomarkers of disease will be checked at time of enrollment, during and at the conclusion of therapy. The cytokine panel will consist of CCL5, IL-6, and Chitinase 3-like 1(Chi3l1).</description>
    <arm_group_label>Maraviroc Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female ≥ 18 years of age at time of screening&#xD;
&#xD;
          -  Documentation of a SARS-CoV-2 diagnosis as evidenced by positive SARS-CoV-2 PCR within&#xD;
             twelve days at time of screening&#xD;
&#xD;
          -  Chest radiography consistent with multi-focal pneumonia or air-space disease&#xD;
&#xD;
          -  Written informed consent obtained from subject and ability for subject to comply with&#xD;
             the requirements of the study.&#xD;
&#xD;
          -  Subject able to safely swallow pills or receive Maraviroc through a nasogastric or&#xD;
             orogastric tube.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who are pregnant, breastfeeding, or unwilling to practice birth control&#xD;
             during participation in the study.&#xD;
&#xD;
          -  Subjects with the presence of a condition or abnormality that in the opinion of the&#xD;
             Investigator would compromise the safety of the patient or the quality of the data.&#xD;
             This includes, but is not limited to, recent myocardial infarction in past 6 months,&#xD;
             neurological, psychiatric, endocrine, or neoplastic diseases that are judged to&#xD;
             interfere with participation in the study.&#xD;
&#xD;
          -  Subjects with known diagnosis of human immunodeficiency virus infection (HIV)&#xD;
&#xD;
          -  Subjects enrolled in another clinical trial (including one for COVID-19) that excludes&#xD;
             participation in other trials or includes a potent CYP3A inhibitor or inducer (e.g.&#xD;
             lopinavir-ritonavir).&#xD;
&#xD;
          -  Subjects with ESRD or severe renal failure who are taking potent (moderate or strong)&#xD;
             CYP3A inhibitors or inducers&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Philip A Chan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Warren Alpert Medical School and School of Public Health, Brown University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rhode Island Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <last_update_submitted>February 2, 2021</last_update_submitted>
  <last_update_submitted_qc>February 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Maraviroc</keyword>
  <keyword>CCR5 Antagonist</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Maraviroc</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04435522
org study id: 1611471-1
nct id: NCT04435522
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Maraviroc, a C-C Chemokine Receptor 5 (CCR5) antagonist, is well-tolerated without
      significant side effects in its current use in patients with HIV. CCR5 antagonism prior to
      the 'second wave' of inflammatory mediator expression in SARS-CoV-2 may reverse lymphoid
      depletion and may alter cell trafficking of inflammatory cells, both increasing viral control
      capacity and dampening damage to lung tissue, respectively. This study seeks to establish
      whether one week of treatment with Maraviroc, used at its approved dosage for HIV, is safe
      and tolerable in patients with SARS-CoV-2.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of Completion
time frame: 7 days
description: Rate of subjects who complete the 7-day course of Maraviroc without discontinuation for serious adverse event or death.
measure: Clinical improvement at Day 7
time frame: 7 days
description: Percent of patients at Day 7 from enrollment achieving reduction of two points on a seven-category ordinal scale (defined below).
Ordinal scale: 1, not hospitalized with resumption of normal activities; 2, not hospitalized, but unable to resume normal activities OR hospitalized pending disposition, not requiring COVID-related care; 3, hospitalized, not requiring supplemental oxygen; 4, hospitalized, requiring supplemental oxygen; 5, hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; 6, hospitalized, requiring ECMO, invasive mechanical ventilation, or both; and, 7, death.
measure: Change in Chitinase 3-like 1(Chi3l1) (ng/mL)
time frame: 7 days
description: Measurement of Chi3l1 before, during and at completion of therapy.
measure: Change in Interleukin-6 (IL-6) (pg/mL)
time frame: 7 Days
description: Measurement of IL-6 before, during and at completion of therapy.
measure: Change in CCL5 (RANTES) (ng/mL)
time frame: 7 Days
description: Measurement of CCL5 before, during and at completion of therapy.
measure: Mortality
time frame: 28 days
description: 7-, 14- and 28-day all-cause-mortality
measure: Time to Discharge
time frame: 28 days
description: Time to improvement to Score of 2 or less (Days)
measure: Days on mechanical ventilation
time frame: 28 days
arm group label: Maraviroc Treatment
arm group type: Experimental
description: Maraviroc 300 mg Twice Daily
intervention type: Drug
intervention name: Maraviroc
description: Maraviroc will be administered for seven days. Biomarkers of disease will be checked at time of enrollment, during and at the conclusion of therapy. The cytokine panel will consist of CCL5, IL-6, and Chitinase 3-like 1(Chi3l1).
arm group label: Maraviroc Treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Philip A Chan, MD
role: Principal Investigator
affiliation: Warren Alpert Medical School and School of Public Health, Brown University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Maraviroc
sharing ipd: No