<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/NCT04498377</url>
  </required_header>
  <id_info>
    <org_study_id>GC-652-04</org_study_id>
    <nct_id>NCT04498377</nct_id>
  </id_info>
  <brief_title>Study of F-652 (IL-22:IgG2 Fusion Protein) in Patients With Moderate to Severe COVID-19</brief_title>
  <official_title>A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation, Multicenter Study to Evaluate the Efficacy and Safety of F-652 (IL-22:IgG2 Fusion Protein) in Patients With Moderate to Severe COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>EVIVE Biotechnology</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>EVIVE Biotechnology</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an interventional, multicenter, 2-arm, parallel-group, randomized, double-blind,&#xD;
      placebo controlled, dose-escalation, safety and efficacy study of F-652 treatment versus&#xD;
      placebo in patients aged 18 years or older with a COVID-19 diagnosis confirmed by PCR.&#xD;
      Eligible patients will have moderate to severe COVID-19 symptoms within 5 days post&#xD;
      hospitalization and a positive COVID-19 testing.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is planned to include 4 cohorts, with enrolled patients being randomized 1:1 in a&#xD;
      blinded manner on Day 1, following screening, to F-652 or placebo as follows:&#xD;
&#xD;
        -  Cohort 1 (sentinel cohort): Four patients will receive either dose level 1 F-652 or&#xD;
           placebo. Upon completion of sentinel, the Data Monitoring Committee will evaluate the&#xD;
           safety and tolerability data of the sentinel patients and determine if it is acceptable&#xD;
           to dose the remaining patients in this dosing group in Cohort 2.&#xD;
&#xD;
        -  Cohort 2: Fourteen patients will receive either dose level 1 F-652 or placebo. Upon&#xD;
           completion of Cohort 2, the DMC will convene and review all available safety data to&#xD;
           determine if the study can proceed to the next dose level.&#xD;
&#xD;
        -  Cohort 3 (sentinel cohort): Four patients will receive either dose level 2 F-652 or&#xD;
           placebo. Upon completion of sentinel dosing, the DMC will evaluate the safety and&#xD;
           tolerability data of the sentinel patients and determine if it is acceptable to dose the&#xD;
           remaining patients in this dosing group in Cohort 4.&#xD;
&#xD;
        -  Cohort 4: Sixteen patients will receive either dose level 2 F-652 or placebo. Treatment&#xD;
           will begin on Day 1 following randomization. Patients assigned to active drug will&#xD;
           receive a total of 2 doses of F-652 (1 IV infusion on Day 1 and 1 IV infusion on Day 8).&#xD;
           Patients assigned to placebo will receive identical IV infusions of placebo vehicle on&#xD;
           Days 1 and 8. All patients will receive available supportive and antiviral therapies as&#xD;
           standard of care. Efficacy will be assessed on Days 15 and 29. Patients will be followed&#xD;
           for safety until Day 60.&#xD;
&#xD;
      The primary efficacy endpoint is the proportion of patients with a ≥2-point increase in the&#xD;
      National Institute of Allergy and Infectious Diseases (NIAID) 8-point ordinal scale from&#xD;
      baseline to Day 29.&#xD;
&#xD;
      The secondary efficacy endpoints include the proportion of patients with a ≥2-point increase&#xD;
      in the NIAID 8-point ordinal scale from baseline to Day 15, mortality rate by Days 15 and 29,&#xD;
      percentage of patients who have recovered and discharged from the hospital by Days 15 and 29,&#xD;
      and percentage of patients progressed to severe/critical disease by Day 15.&#xD;
&#xD;
      The safety endpoints include all cause treatment-emergent adverse events (TEAEs) and serious&#xD;
      adverse events (SAEs); change from screening (baseline) in clinical symptoms and abnormal&#xD;
      vital signs, abnormal laboratory tests; and relationship of any AEs with F-652 treatment.&#xD;
&#xD;
      The exploratory endpoints include time to negative SARS-CoV-2 PCR test from randomization;&#xD;
      and changes in pharmacodynamic parameters.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    There have been significant changes in the FDA guidelines and clinical standard of care&#xD;
  </why_stopped>
  <start_date type="Actual">January 26, 2021</start_date>
  <completion_date type="Actual">March 24, 2021</completion_date>
  <primary_completion_date type="Actual">March 24, 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Patients will be randomized in a 1:1 ratio in a double-blind manner to receive F-652 or placebo.&#xD;
An independent statistician from Medpace will generate the randomization schedule. Patients meeting eligibility criteria will be randomized on Day 1 in a 1:1 ratio to F-652 or placebo, respectively. Patients will be assigned a randomization number and treatment assignment according to the randomization schedule. This randomization schedule will be maintained by the investigative site pharmacist until it is appropriate to break the blind. The Investigator, investigative site personnel (except site-designated pharmacist and dedicated assistant), study monitors, vendors, Sponsor, and Medpace will remain blinded to treatment assignment.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>NIAID 8-point ordinal scale</measure>
    <time_frame>Study day 1 before dose to day 29</time_frame>
    <description>The proportion of patients with a greater or equal 2-point change in the NIAID 8-point ordinal scale from baseline to Day 29</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Covid19</condition>
  <arm_group>
    <arm_group_label>F-652</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>F-652</intervention_name>
    <description>IL-22 fusion protein administered intravenously</description>
    <arm_group_label>F-652</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo administered intravenously</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Willing to provide informed consent and able to comply with protocol requirements&#xD;
&#xD;
          -  18 years or older&#xD;
&#xD;
          -  Has a COVID-19 diagnosis confirmed by PCR&#xD;
&#xD;
          -  Hospitalized within 5 days and meets the following criteria at screening:&#xD;
&#xD;
        Peripheral capillary oxygen saturation (SpO2) ≤ 93% on room air or SpO2 ≥93% on ≤10 liters&#xD;
        per minute of supplemental oxygen via nasal cannula&#xD;
&#xD;
          -  Radiographic (chest X-ray, computed tomography scan, or ultrasound) evidence of&#xD;
             bilateral pulmonary infiltrates consistent with SARS-CoV-2/COVID-19&#xD;
&#xD;
          -  Clinical symptoms consistent with COVID-19 per Investigator judgement&#xD;
&#xD;
          -  Body mass index between 18 to 40 kg/m2&#xD;
&#xD;
          -  If of reproductive potential, willing to abstain or agree to the use of highly&#xD;
             effective contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Respiratory failure at screening&#xD;
&#xD;
          -  History of heart failure&#xD;
&#xD;
          -  History of COPD or bronchial asthma&#xD;
&#xD;
          -  Active TB or history of TB of the following types&#xD;
&#xD;
          -  Uncontrolled arrhythmia within 3 months prior to randomization&#xD;
&#xD;
          -  Heart disease of the following types&#xD;
&#xD;
          -  Moderate to severe renal insufficiency&#xD;
&#xD;
          -  Abnormal white cell and platelet counts&#xD;
&#xD;
          -  History of transplantation of vital organs (e.g., heart, lung, liver, and/or kidney);&#xD;
&#xD;
          -  Malignant tumor&#xD;
&#xD;
          -  Uncontrolled systemic or local autoimmune or inflammatory disease besides SARS-CoV-2&#xD;
&#xD;
          -  Unhealed wounds, active gastric ulcer, had surgery&#xD;
&#xD;
          -  Received other investigational therapeutic products&#xD;
&#xD;
          -  Used interferon therapies&#xD;
&#xD;
          -  History of HIV infection, hepatitis B, and/or hepatitis C&#xD;
&#xD;
          -  Known serious allergic reaction or hypersensitivity to components of F-652&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  History of drug abuse or use of narcotics&#xD;
&#xD;
          -  Treated with immunomodulators or immunosuppressants&#xD;
&#xD;
          -  Other conditions resulting in increased risk&#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>Christine M Bojanowski, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tulane University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tulane University School of Medicine</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>July 31, 2020</study_first_submitted>
  <study_first_submitted_qc>July 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2020</study_first_posted>
  <last_update_submitted>January 29, 2022</last_update_submitted>
  <last_update_submitted_qc>January 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_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/NCT04498377
org study id: GC-652-04
nct id: NCT04498377
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is an interventional, multicenter, 2-arm, parallel-group, randomized, double-blind,
      placebo controlled, dose-escalation, safety and efficacy study of F-652 treatment versus
      placebo in patients aged 18 years or older with a COVID-19 diagnosis confirmed by PCR.
      Eligible patients will have moderate to severe COVID-19 symptoms within 5 days post
      hospitalization and a positive COVID-19 testing.
The study is planned to include 4 cohorts, with enrolled patients being randomized 1:1 in a
      blinded manner on Day 1, following screening, to F-652 or placebo as follows:

        -  Cohort 1 (sentinel cohort): Four patients will receive either dose level 1 F-652 or
           placebo. Upon completion of sentinel, the Data Monitoring Committee will evaluate the
           safety and tolerability data of the sentinel patients and determine if it is acceptable
           to dose the remaining patients in this dosing group in Cohort 2.

        -  Cohort 2: Fourteen patients will receive either dose level 1 F-652 or placebo. Upon
           completion of Cohort 2, the DMC will convene and review all available safety data to
           determine if the study can proceed to the next dose level.

        -  Cohort 3 (sentinel cohort): Four patients will receive either dose level 2 F-652 or
           placebo. Upon completion of sentinel dosing, the DMC will evaluate the safety and
           tolerability data of the sentinel patients and determine if it is acceptable to dose the
           remaining patients in this dosing group in Cohort 4.

        -  Cohort 4: Sixteen patients will receive either dose level 2 F-652 or placebo. Treatment
           will begin on Day 1 following randomization. Patients assigned to active drug will
           receive a total of 2 doses of F-652 (1 IV infusion on Day 1 and 1 IV infusion on Day 8).
           Patients assigned to placebo will receive identical IV infusions of placebo vehicle on
           Days 1 and 8. All patients will receive available supportive and antiviral therapies as
           standard of care. Efficacy will be assessed on Days 15 and 29. Patients will be followed
           for safety until Day 60.

      The primary efficacy endpoint is the proportion of patients with a ≥2-point increase in the
      National Institute of Allergy and Infectious Diseases (NIAID) 8-point ordinal scale from
      baseline to Day 29.

      The secondary efficacy endpoints include the proportion of patients with a ≥2-point increase
      in the NIAID 8-point ordinal scale from baseline to Day 15, mortality rate by Days 15 and 29,
      percentage of patients who have recovered and discharged from the hospital by Days 15 and 29,
      and percentage of patients progressed to severe/critical disease by Day 15.

      The safety endpoints include all cause treatment-emergent adverse events (TEAEs) and serious
      adverse events (SAEs); change from screening (baseline) in clinical symptoms and abnormal
      vital signs, abnormal laboratory tests; and relationship of any AEs with F-652 treatment.

      The exploratory endpoints include time to negative SARS-CoV-2 PCR test from randomization;
      and changes in pharmacodynamic parameters.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Patients will be randomized in a 1:1 ratio in a double-blind manner to receive F-652 or placebo.
An independent statistician from Medpace will generate the randomization schedule. Patients meeting eligibility criteria will be randomized on Day 1 in a 1:1 ratio to F-652 or placebo, respectively. Patients will be assigned a randomization number and treatment assignment according to the randomization schedule. This randomization schedule will be maintained by the investigative site pharmacist until it is appropriate to break the blind. The Investigator, investigative site personnel (except site-designated pharmacist and dedicated assistant), study monitors, vendors, Sponsor, and Medpace will remain blinded to treatment assignment.
measure: NIAID 8-point ordinal scale
time frame: Study day 1 before dose to day 29
description: The proportion of patients with a greater or equal 2-point change in the NIAID 8-point ordinal scale from baseline to Day 29
arm group label: F-652
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Biological
intervention name: F-652
description: IL-22 fusion protein administered intravenously
arm group label: F-652
intervention type: Biological
intervention name: Placebo
description: Placebo administered intravenously
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Christine M Bojanowski, MD
role: Principal Investigator
affiliation: Tulane University
facility: 
country: United States
responsible party type: Sponsor
mesh term: COVID-19
sharing ipd: No