<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/NCT04399798</url>
  </required_header>
  <id_info>
    <org_study_id>2020-001185-11</org_study_id>
    <nct_id>NCT04399798</nct_id>
  </id_info>
  <brief_title>Baricitinib for coRona Virus pnEumonia (COVID-19): a THerapeutic Trial</brief_title>
  <acronym>BREATH</acronym>
  <official_title>A proof-of Concept Study of the Use of Janus Kinase 1 and 2 Inhibitor, Baricitinib, in the Treatment of COVID-19-related Pneumonia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>IRCCS Policlinico S. Matteo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>IRCCS Policlinico S. Matteo</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 objective of the study is to assess the efficacy and safety of Baricitinib in the&#xD;
      treatment of patients with COVID-19 pneumonia.&#xD;
&#xD;
      This will be a proof-of-concept trial with an exploratory single-arm proof of concept Phase&#xD;
      IIa study to assess the efficacy and safety profile of Baricitinib in a limited number of&#xD;
      patients with severe acute respiratory syndrome (SARS)-CoV-2 pneumonia. If the initial proof&#xD;
      of concept phase will lead to favourable results, an open-label, Phase II, randomized&#xD;
      controlled trial will be then designed and performed to confirm the results obtained in the&#xD;
      proof of concept phase. The proof-of-concept phase guarantees that no safety issues arise on&#xD;
      a limited number of patients in the use of a drug new to the current condition being treated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Baricitinib 4 mg/daily will be prescribed for 7 days to eligible patients showing signs of&#xD;
      acute inflammatory response activation. The primary outcome of the study will be the response&#xD;
      to treatment. A patient is considered responder in the absence of either moderate to severe&#xD;
      oxygenation impairment or death, whichever occurs first, within 8 days from enrolment. The&#xD;
      main secondary outcomes will include the responder rate and mortality at 15 days, the&#xD;
      quantification of patients experiencing moderate to severe oxygenation impairment, rate of&#xD;
      patients admitted to the intensive care unit, length of hospitalization, mortality at 28&#xD;
      days, rate of re-admission, and adverse events. The duration of the study will be 28 days. In&#xD;
      the proof of concept phase, 13 patients will be enrolled; if the responders will be at least&#xD;
      4 patients without safety issues, Baricitinib will be considered for further studies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">May 15, 2020</start_date>
  <completion_date type="Anticipated">November 15, 2020</completion_date>
  <primary_completion_date type="Anticipated">September 15, 2020</primary_completion_date>
  <phase>Phase 2</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>
    <intervention_model_description>Proof-of-concept trial with an exploratory single-arm proof of concept Phase IIa study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Response to treatment: absence of moderate to severe oxygenation impairment (Berlin criteria)</measure>
    <time_frame>8 days</time_frame>
    <description>A patient is consider responder in the absence of either moderate to severe oxygenation impairment according to Berlin criteria - measured as Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Response to treatment: survival</measure>
    <time_frame>8 days</time_frame>
    <description>Absence of death within 8 days from enrollment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To quantify the rate of each of: moderate or severe oxygenation impairment within 8 days</measure>
    <time_frame>8 days</time_frame>
    <description>Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To quantify the rate of each of: moderate or severe oxygenation impairment within 15 days</measure>
    <time_frame>15 days</time_frame>
    <description>Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>8 days and 15 days</time_frame>
    <description>To quantify mortality within 8 and 15 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peripheral capillary oxygen saturation (SpO2)</measure>
    <time_frame>8 days; 15 days</time_frame>
    <description>SpO2 will be assessed with the median and 25th-75th percentiles</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2)</measure>
    <time_frame>8 days; 15 days</time_frame>
    <description>PaO2/FiO2 will be assessed with the median and 25th-75th percentiles</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess the rate of patients admitted to the intensive care unit</measure>
    <time_frame>8 days; 15 days</time_frame>
    <description>Number of patients over the number of patients enrolled</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To measure the length of hospital stay</measure>
    <time_frame>8 days; 15 days</time_frame>
    <description>Median number of days and 25th-75th percentiles</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>28-day mortality</measure>
    <time_frame>28 days</time_frame>
    <description>To quantify 28-day mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To quantify the rate of re-admission within 28 days</measure>
    <time_frame>28 days</time_frame>
    <description>Number of patients readmitted over the number patients enrolled</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To quantify the cumulative incidence and severity of adverse events</measure>
    <time_frame>28 days</time_frame>
    <description>Number, type, and severity of adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interleukin (IL)-1; IL-2; IL-10; IL-6; IL-8; IL-17; IL-2 receptor levels;</measure>
    <time_frame>15 days</time_frame>
    <description>Serial serum assessments from baseline up to 15 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TNFalpha; vascular endothelial growth factor (VEGF); interferon gamma (IFNgamma) levels</measure>
    <time_frame>15 days</time_frame>
    <description>Serial serum assessments from baseline up to 15 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Viral load analyses</measure>
    <time_frame>15 days</time_frame>
    <description>Serial assessments from baseline up to 15 days for viral load persistence</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">13</enrollment>
  <condition>Corona Virus Infection</condition>
  <arm_group>
    <arm_group_label>Baricitinib active treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Baricitinib 4 mg/day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Baricitinib</intervention_name>
    <description>4 mg/day for 7 days</description>
    <arm_group_label>Baricitinib active treatment</arm_group_label>
    <other_name>Olumiant</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ability to obtain informed patient consent noting the limitations of existing&#xD;
             knowledge regarding Baricitinib's efficacy and the labeled warning and precautions as&#xD;
             the proposed use is outside the approved indication, as well as the presence of known&#xD;
             risk of being treated with Baricitinib while the subject of an active infection&#xD;
&#xD;
          -  informed Consent as documented by signature&#xD;
&#xD;
          -  patients with a confirmed SARS-CoV-2 pneumonia&#xD;
&#xD;
          -  adult patients aged 18-74 years old&#xD;
&#xD;
          -  infiltrates at chest radiography&#xD;
&#xD;
          -  c-reactive protein level greater than 10 mg/dl or ferritin level &gt; 900 ug/L&#xD;
&#xD;
          -  Lymphocyte count less than 1500/mmc&#xD;
&#xD;
          -  &gt; 200 PaO2/FiO2 ≤ 300&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  patients aged &lt; 18 years old and ≥ 75 years old&#xD;
&#xD;
          -  concomitant bacterial infection&#xD;
&#xD;
          -  lymphopenia less than 500/mmc&#xD;
&#xD;
          -  hemoglobin &lt; 8 g/dl&#xD;
&#xD;
          -  absolute neutrophil count &lt; 1 x 109 cells/L&#xD;
&#xD;
          -  requiring continuous positive airway pressure (C-PAP) or mechanical ventilation&#xD;
&#xD;
          -  sudden clinical deterioration requiring intensive care unit access&#xD;
&#xD;
          -  known hypersensitivity or allergy to the study drug&#xD;
&#xD;
          -  Creatinine clearance &lt; 30 mL/min; if the creatinine clearance is between 30 and 60&#xD;
             mL/min the dose of Baricitinib should be reduced to 2 mg/daily&#xD;
&#xD;
          -  Severe hepatic impairment (no dose adjustment of Baricitinib is required in mild or&#xD;
             moderate hepatic impairment)&#xD;
&#xD;
          -  Pregnant or breast-feeding&#xD;
&#xD;
          -  Active tuberculosis&#xD;
&#xD;
          -  Evidence of active hepatitis B (HBV) (HbsAg positive) or with detectable hepatitis C&#xD;
             virus (HCV)-RNA, human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Ongoing, acute diagnosis of deep venous thrombosis/pulmonary embolism (DVT/PE)&#xD;
&#xD;
          -  Previous diagnosis of DVT/PE&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>74 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carlomaurizio Montecucco, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rheumatology, IRCCS Fondazione Policlinico S. Matteo, Pavia, Italy</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Raffaele Bruno, Prof</last_name>
    <role>Study Chair</role>
    <affiliation>Infectious Diseases; IRCCS Fondazione Policlinico S. Matteo, Pavia, Italy</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sara Monti, MD</last_name>
    <phone>0382501878</phone>
    <email>sara.saramonti@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Valentina Zuccaro, MD</last_name>
    <phone>0382501080</phone>
    <email>V.Zuccaro@smatteo.pv.it</email>
  </overall_contact_backup>
  <reference>
    <citation>Richardson P, Griffin I, Tucker C, Smith D, Oechsle O, Phelan A, Rawling M, Savory E, Stebbing J. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet. 2020 Feb 15;395(10223):e30-e31. doi: 10.1016/S0140-6736(20)30304-4. Epub 2020 Feb 4. No abstract available. Erratum In: Lancet. 2020 Jun 20;395(10241):1906.</citation>
    <PMID>32032529</PMID>
  </reference>
  <reference>
    <citation>Stebbing J, Phelan A, Griffin I, Tucker C, Oechsle O, Smith D, Richardson P. COVID-19: combining antiviral and anti-inflammatory treatments. Lancet Infect Dis. 2020 Apr;20(4):400-402. doi: 10.1016/S1473-3099(20)30132-8. Epub 2020 Feb 27. No abstract available.</citation>
    <PMID>32113509</PMID>
  </reference>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 13, 2020</study_first_submitted>
  <study_first_submitted_qc>May 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 22, 2020</study_first_posted>
  <last_update_submitted>May 21, 2020</last_update_submitted>
  <last_update_submitted_qc>May 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>IRCCS Policlinico S. Matteo</investigator_affiliation>
    <investigator_full_name>Carlomaurizio Montecucco</investigator_full_name>
    <investigator_title>Prof</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia</mesh_term>
    <mesh_term>Coronavirus Infections</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/NCT04399798
org study id: 2020-001185-11
nct id: NCT04399798
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The objective of the study is to assess the efficacy and safety of Baricitinib in the
      treatment of patients with COVID-19 pneumonia.

      This will be a proof-of-concept trial with an exploratory single-arm proof of concept Phase
      IIa study to assess the efficacy and safety profile of Baricitinib in a limited number of
      patients with severe acute respiratory syndrome (SARS)-CoV-2 pneumonia. If the initial proof
      of concept phase will lead to favourable results, an open-label, Phase II, randomized
      controlled trial will be then designed and performed to confirm the results obtained in the
      proof of concept phase. The proof-of-concept phase guarantees that no safety issues arise on
      a limited number of patients in the use of a drug new to the current condition being treated.
Baricitinib 4 mg/daily will be prescribed for 7 days to eligible patients showing signs of
      acute inflammatory response activation. The primary outcome of the study will be the response
      to treatment. A patient is considered responder in the absence of either moderate to severe
      oxygenation impairment or death, whichever occurs first, within 8 days from enrolment. The
      main secondary outcomes will include the responder rate and mortality at 15 days, the
      quantification of patients experiencing moderate to severe oxygenation impairment, rate of
      patients admitted to the intensive care unit, length of hospitalization, mortality at 28
      days, rate of re-admission, and adverse events. The duration of the study will be 28 days. In
      the proof of concept phase, 13 patients will be enrolled; if the responders will be at least
      4 patients without safety issues, Baricitinib will be considered for further studies.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Proof-of-concept trial with an exploratory single-arm proof of concept Phase IIa study
primary purpose: Treatment
masking: None (Open Label)
measure: Response to treatment: absence of moderate to severe oxygenation impairment (Berlin criteria)
time frame: 8 days
description: A patient is consider responder in the absence of either moderate to severe oxygenation impairment according to Berlin criteria - measured as Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2)
measure: Response to treatment: survival
time frame: 8 days
description: Absence of death within 8 days from enrollment
measure: To quantify the rate of each of: moderate or severe oxygenation impairment within 8 days
time frame: 8 days
description: Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)
measure: To quantify the rate of each of: moderate or severe oxygenation impairment within 15 days
time frame: 15 days
description: Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)
measure: Mortality
time frame: 8 days and 15 days
description: To quantify mortality within 8 and 15 days
measure: Peripheral capillary oxygen saturation (SpO2)
time frame: 8 days; 15 days
description: SpO2 will be assessed with the median and 25th-75th percentiles
measure: Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2)
time frame: 8 days; 15 days
description: PaO2/FiO2 will be assessed with the median and 25th-75th percentiles
measure: To assess the rate of patients admitted to the intensive care unit
time frame: 8 days; 15 days
description: Number of patients over the number of patients enrolled
measure: To measure the length of hospital stay
time frame: 8 days; 15 days
description: Median number of days and 25th-75th percentiles
measure: 28-day mortality
time frame: 28 days
description: To quantify 28-day mortality
measure: To quantify the rate of re-admission within 28 days
time frame: 28 days
description: Number of patients readmitted over the number patients enrolled
measure: To quantify the cumulative incidence and severity of adverse events
time frame: 28 days
description: Number, type, and severity of adverse events
measure: Interleukin (IL)-1; IL-2; IL-10; IL-6; IL-8; IL-17; IL-2 receptor levels;
time frame: 15 days
description: Serial serum assessments from baseline up to 15 days
measure: TNFalpha; vascular endothelial growth factor (VEGF); interferon gamma (IFNgamma) levels
time frame: 15 days
description: Serial serum assessments from baseline up to 15 days
measure: Viral load analyses
time frame: 15 days
description: Serial assessments from baseline up to 15 days for viral load persistence
arm group label: Baricitinib active treatment
arm group type: Experimental
description: Baricitinib 4 mg/day
intervention type: Drug
intervention name: Baricitinib
description: 4 mg/day for 7 days
arm group label: Baricitinib active treatment
other name: Olumiant
criteria: 
gender: All
minimum age: 18 Years
maximum age: 74 Years
healthy volunteers: No
last name: Carlomaurizio Montecucco, Prof
role: Principal Investigator
affiliation: Rheumatology, IRCCS Fondazione Policlinico S. Matteo, Pavia, Italy
last name: Raffaele Bruno, Prof
role: Study Chair
affiliation: Infectious Diseases; IRCCS Fondazione Policlinico S. Matteo, Pavia, Italy
last name: Sara Monti, MD
phone: 0382501878
email: sara.saramonti@gmail.com
last name: Valentina Zuccaro, MD
phone: 0382501080
email: V.Zuccaro@smatteo.pv.it
citation: Richardson P, Griffin I, Tucker C, Smith D, Oechsle O, Phelan A, Rawling M, Savory E, Stebbing J. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet. 2020 Feb 15;395(10223):e30-e31. doi: 10.1016/S0140-6736(20)30304-4. Epub 2020 Feb 4. No abstract available. Erratum In: Lancet. 2020 Jun 20;395(10241):1906.
PMID: 32032529
citation: Stebbing J, Phelan A, Griffin I, Tucker C, Oechsle O, Smith D, Richardson P. COVID-19: combining antiviral and anti-inflammatory treatments. Lancet Infect Dis. 2020 Apr;20(4):400-402. doi: 10.1016/S1473-3099(20)30132-8. Epub 2020 Feb 27. No abstract available.
PMID: 32113509
responsible party type: Principal Investigator
investigator affiliation: IRCCS Policlinico S. Matteo
investigator full name: Carlomaurizio Montecucco
investigator title: Prof
mesh term: Pneumonia
mesh term: Coronavirus Infections
sharing ipd: No