<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/NCT04449380</url>
  </required_header>
  <id_info>
    <org_study_id>INTERCOP</org_study_id>
    <nct_id>NCT04449380</nct_id>
  </id_info>
  <brief_title>Clinical Study for the Treatment With Interferon-ß-1a (IFNß-1a) of COVID-19 Patients</brief_title>
  <acronym>INTERCOP</acronym>
  <official_title>Randomized, Controlled, Open Label, Phase 2 Clinical Trial of Interferon-β-1a (IFNβ-1a) in COVID-19 Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emanuele Bosi</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>IRCCS San Raffaele</source>
  <oversight_info>
    <has_dmc>No</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>
      Pharmacological therapies of proven efficacy in coronavirus disease 2019 (COVID-19) are still&#xD;
      lacking.&#xD;
&#xD;
      Since two clinical stages of COVID-19 are emerging, an early one with typical clinical&#xD;
      characteristics of a viral infection (fever, malaise, cough) and a later one with pneumonia&#xD;
      leading to progressive respiratory failure, associated with heavy, cytokine-mediated,&#xD;
      inflammation, an intervention by a compound possessing both antiviral activity and&#xD;
      immunomodulatory effects would be most effective at the earliest possible stage.&#xD;
&#xD;
      The purpose of this clinical trial is to test the efficacy of Interferon-β-1a (IFNβ-1a), in&#xD;
      COVID-19 patients in an open label, randomized clinical trial.&#xD;
&#xD;
      The design of the study is to test IFNβ-1a in addition to standard of care compared with&#xD;
      standard of care alone.&#xD;
&#xD;
      The primary outcome is the time to negative conversion of Severe Acute Respiratory&#xD;
      Syndrome-CoronaVirus-2 (SARS-CoV-2) nasopharyngeal swabs.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Futility&#xD;
  </why_stopped>
  <start_date type="Actual">November 2, 2020</start_date>
  <completion_date type="Actual">March 30, 2021</completion_date>
  <primary_completion_date type="Actual">March 30, 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>This is an interventional, monocentric, phase 2, randomized (2:1), open label, controlled clinical study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to negative conversion of SARS-CoV-2 nasopharyngeal swab</measure>
    <time_frame>From baseline to day 29</time_frame>
    <description>Viral load will be measured by Real Time-Polymerase Chain Reaction (RT-PCR)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Improvement in clinical severity score (a)</measure>
    <time_frame>Baseline, days 7, 15, 21, 29</time_frame>
    <description>Defined as percentage of patients reporting each severity rating on a 7-point ordinal scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in clinical severity score (b)</measure>
    <time_frame>Baseline, days 7, 15, 21, 29</time_frame>
    <description>Defined as the time to clinical improvement of two points from the time of randomization on a 7-category ordinal scale or live discharge from the hospital, whichever comes first</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of new oxygen use, non-invasive ventilation, or high flow oxygen devices during the trial</measure>
    <time_frame>From baseline to day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxygenation free days in the first 28 days</measure>
    <time_frame>From baseline to day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilator free days in the first 28 days</measure>
    <time_frame>From baseline to day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of new mechanical ventilation use during the trial</measure>
    <time_frame>From baseline to day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients transferred to Intensive Care Unit (ICU)</measure>
    <time_frame>From baseline to day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality rate</measure>
    <time_frame>From baseline to day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in pulmonary computed tomography (CT) imaging severity score</measure>
    <time_frame>Baseline, day 21; extra follow up at 90 days</time_frame>
    <description>Measured with artificial intelligence and expressed as cc and percent values of diseased lung (lung consolidation, ground glass opacities and disease free)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of hospital stay expressed in days</measure>
    <time_frame>From baseline to day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Viral load measured on plasma with RT-PCR</measure>
    <time_frame>Baseline, days 3, 5, 7, 9, 11, 13, 15, 21, 29</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Plasma and peripheral blood mononuclear cell messenger-RNA (mRNA) expression profile of interferon stimulated genes (ISG)</measure>
    <time_frame>Baseline, day 15</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Antibodies to SARS-CoV-2</measure>
    <time_frame>Baseline, days 7, 15, 29</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Antibodies to IFN-β1a</measure>
    <time_frame>Baseline, days 7, 15, 29</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">56</enrollment>
  <condition>COVID-19 Virus Infection</condition>
  <arm_group>
    <arm_group_label>IFNβ 1a</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Interferon-ß-1a</intervention_name>
    <description>IFNβ-1a will be administered subcutaneously at a dose of 44 mcg (equivalent to 12 million international units), three times per week at least 48 hours apart, for a total of two weeks. All patients will receive a total dose of 264 mcg (72 million international units) under physician control</description>
    <arm_group_label>IFNβ 1a</arm_group_label>
    <other_name>IFNß-1a</other_name>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Standard of Care (SOC)</intervention_name>
    <description>Any pharmacological (e.g. antibiotics, etc.) and non-pharmacological (e.g. oxygen, ventilation, etc.) treatments prescribed on clinical grounds</description>
    <arm_group_label>Standard care</arm_group_label>
    <other_name>SOC</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Informed consent signed&#xD;
&#xD;
          2. Patients hospitalized with confirmed swab RT-PCR detection of SARS-CoV-2&#xD;
&#xD;
          3. X-ray and/or CT diagnosed pneumonia&#xD;
&#xD;
          4. Age &gt;=18 years&#xD;
&#xD;
          5. Clinical status defined as 3, 4 or 5 on the 7-point ordinal scale&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known allergy or hypersensitivity to IFNß-1a or IFNß-1b&#xD;
&#xD;
          2. Presence of severe concomitant illnesses/medical conditions that in the physician&#xD;
             opinion do not allow participation to the study&#xD;
&#xD;
          3. Pregnant or lactating females&#xD;
&#xD;
          4. History of major depression disorder or suicidal attempt or suicidal ideation&#xD;
&#xD;
          5. Spontaneous blood alanine aminotransferase/aspartate aminotransferase (ALT/AST) levels&#xD;
             &gt; 5 times the upper limit of normal&#xD;
&#xD;
          6. Clinical status defined as 1, 2, or 6 on the 7-point ordinal scale&#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>Emanuele Bosi, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>IRCCS Ospedale San Raffaele</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>IRCCS Ospedale San Raffaele</name>
      <address>
        <city>Milano</city>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>June 23, 2020</study_first_submitted>
  <study_first_submitted_qc>June 25, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 26, 2020</study_first_posted>
  <last_update_submitted>April 28, 2021</last_update_submitted>
  <last_update_submitted_qc>April 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>IRCCS San Raffaele</investigator_affiliation>
    <investigator_full_name>Emanuele Bosi</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <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>Interferons</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04449380
org study id: INTERCOP
nct id: NCT04449380
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Pharmacological therapies of proven efficacy in coronavirus disease 2019 (COVID-19) are still
      lacking.

      Since two clinical stages of COVID-19 are emerging, an early one with typical clinical
      characteristics of a viral infection (fever, malaise, cough) and a later one with pneumonia
      leading to progressive respiratory failure, associated with heavy, cytokine-mediated,
      inflammation, an intervention by a compound possessing both antiviral activity and
      immunomodulatory effects would be most effective at the earliest possible stage.

      The purpose of this clinical trial is to test the efficacy of Interferon-β-1a (IFNβ-1a), in
      COVID-19 patients in an open label, randomized clinical trial.

      The design of the study is to test IFNβ-1a in addition to standard of care compared with
      standard of care alone.

      The primary outcome is the time to negative conversion of Severe Acute Respiratory
      Syndrome-CoronaVirus-2 (SARS-CoV-2) nasopharyngeal swabs.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is an interventional, monocentric, phase 2, randomized (2:1), open label, controlled clinical study
primary purpose: Treatment
masking: None (Open Label)
measure: Time to negative conversion of SARS-CoV-2 nasopharyngeal swab
time frame: From baseline to day 29
description: Viral load will be measured by Real Time-Polymerase Chain Reaction (RT-PCR)
measure: Improvement in clinical severity score (a)
time frame: Baseline, days 7, 15, 21, 29
description: Defined as percentage of patients reporting each severity rating on a 7-point ordinal scale
measure: Improvement in clinical severity score (b)
time frame: Baseline, days 7, 15, 21, 29
description: Defined as the time to clinical improvement of two points from the time of randomization on a 7-category ordinal scale or live discharge from the hospital, whichever comes first
measure: Incidence of new oxygen use, non-invasive ventilation, or high flow oxygen devices during the trial
time frame: From baseline to day 29
measure: Oxygenation free days in the first 28 days
time frame: From baseline to day 29
measure: Ventilator free days in the first 28 days
time frame: From baseline to day 29
measure: Incidence of new mechanical ventilation use during the trial
time frame: From baseline to day 29
measure: Number of patients transferred to Intensive Care Unit (ICU)
time frame: From baseline to day 29
measure: Mortality rate
time frame: From baseline to day 29
measure: Changes from baseline in pulmonary computed tomography (CT) imaging severity score
time frame: Baseline, day 21; extra follow up at 90 days
description: Measured with artificial intelligence and expressed as cc and percent values of diseased lung (lung consolidation, ground glass opacities and disease free)
measure: Duration of hospital stay expressed in days
time frame: From baseline to day 29
measure: Viral load measured on plasma with RT-PCR
time frame: Baseline, days 3, 5, 7, 9, 11, 13, 15, 21, 29
measure: Plasma and peripheral blood mononuclear cell messenger-RNA (mRNA) expression profile of interferon stimulated genes (ISG)
time frame: Baseline, day 15
measure: Antibodies to SARS-CoV-2
time frame: Baseline, days 7, 15, 29
measure: Antibodies to IFN-β1a
time frame: Baseline, days 7, 15, 29
arm group label: IFNβ 1a
arm group type: Experimental
arm group label: Standard care
arm group type: Active Comparator
intervention type: Drug
intervention name: Interferon-ß-1a
description: IFNβ-1a will be administered subcutaneously at a dose of 44 mcg (equivalent to 12 million international units), three times per week at least 48 hours apart, for a total of two weeks. All patients will receive a total dose of 264 mcg (72 million international units) under physician control
arm group label: IFNβ 1a
other name: IFNß-1a
intervention type: Combination Product
intervention name: Standard of Care (SOC)
description: Any pharmacological (e.g. antibiotics, etc.) and non-pharmacological (e.g. oxygen, ventilation, etc.) treatments prescribed on clinical grounds
arm group label: Standard care
other name: SOC
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Emanuele Bosi, Professor
role: Principal Investigator
affiliation: IRCCS Ospedale San Raffaele
facility: 
country: Italy
responsible party type: Sponsor-Investigator
investigator affiliation: IRCCS San Raffaele
investigator full name: Emanuele Bosi
investigator title: Professor
mesh term: COVID-19
mesh term: Interferons