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Baricitinib for coRona Virus pnEumonia (COVID-19): a THerapeutic Trial (BREATH)

Primary Purpose

Corona Virus Infection

Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Baricitinib
Sponsored by
IRCCS Policlinico S. Matteo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Corona Virus Infection

Eligibility Criteria

18 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Ability to obtain informed patient consent noting the limitations of existing knowledge regarding Baricitinib's efficacy and the labeled warning and precautions as the proposed use is outside the approved indication, as well as the presence of known risk of being treated with Baricitinib while the subject of an active infection
  • informed Consent as documented by signature
  • patients with a confirmed SARS-CoV-2 pneumonia
  • adult patients aged 18-74 years old
  • infiltrates at chest radiography
  • c-reactive protein level greater than 10 mg/dl or ferritin level > 900 ug/L
  • Lymphocyte count less than 1500/mmc
  • > 200 PaO2/FiO2 ≤ 300

Exclusion Criteria:

  • patients aged < 18 years old and ≥ 75 years old
  • concomitant bacterial infection
  • lymphopenia less than 500/mmc
  • hemoglobin < 8 g/dl
  • absolute neutrophil count < 1 x 109 cells/L
  • requiring continuous positive airway pressure (C-PAP) or mechanical ventilation
  • sudden clinical deterioration requiring intensive care unit access
  • known hypersensitivity or allergy to the study drug
  • Creatinine clearance < 30 mL/min; if the creatinine clearance is between 30 and 60 mL/min the dose of Baricitinib should be reduced to 2 mg/daily
  • Severe hepatic impairment (no dose adjustment of Baricitinib is required in mild or moderate hepatic impairment)
  • Pregnant or breast-feeding
  • Active tuberculosis
  • Evidence of active hepatitis B (HBV) (HbsAg positive) or with detectable hepatitis C virus (HCV)-RNA, human immunodeficiency virus (HIV)
  • Ongoing, acute diagnosis of deep venous thrombosis/pulmonary embolism (DVT/PE)
  • Previous diagnosis of DVT/PE

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Baricitinib active treatment

    Arm Description

    Baricitinib 4 mg/day

    Outcomes

    Primary Outcome Measures

    Response to treatment: absence of moderate to severe oxygenation impairment (Berlin criteria)
    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)
    Response to treatment: survival
    Absence of death within 8 days from enrollment

    Secondary Outcome Measures

    To quantify the rate of each of: moderate or severe oxygenation impairment within 8 days
    Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)
    To quantify the rate of each of: moderate or severe oxygenation impairment within 15 days
    Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)
    Mortality
    To quantify mortality within 8 and 15 days
    Peripheral capillary oxygen saturation (SpO2)
    SpO2 will be assessed with the median and 25th-75th percentiles
    Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2)
    PaO2/FiO2 will be assessed with the median and 25th-75th percentiles
    To assess the rate of patients admitted to the intensive care unit
    Number of patients over the number of patients enrolled
    To measure the length of hospital stay
    Median number of days and 25th-75th percentiles
    28-day mortality
    To quantify 28-day mortality
    To quantify the rate of re-admission within 28 days
    Number of patients readmitted over the number patients enrolled
    To quantify the cumulative incidence and severity of adverse events
    Number, type, and severity of adverse events
    Interleukin (IL)-1; IL-2; IL-10; IL-6; IL-8; IL-17; IL-2 receptor levels;
    Serial serum assessments from baseline up to 15 days
    TNFalpha; vascular endothelial growth factor (VEGF); interferon gamma (IFNgamma) levels
    Serial serum assessments from baseline up to 15 days
    Viral load analyses
    Serial assessments from baseline up to 15 days for viral load persistence

    Full Information

    First Posted
    May 13, 2020
    Last Updated
    May 21, 2020
    Sponsor
    IRCCS Policlinico S. Matteo
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04399798
    Brief Title
    Baricitinib for coRona Virus pnEumonia (COVID-19): a THerapeutic Trial
    Acronym
    BREATH
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2020
    Overall Recruitment Status
    Unknown status
    Study Start Date
    May 15, 2020 (Anticipated)
    Primary Completion Date
    September 15, 2020 (Anticipated)
    Study Completion Date
    November 15, 2020 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    IRCCS Policlinico S. Matteo

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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.
    Detailed Description
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Corona Virus Infection

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Model Description
    Proof-of-concept trial with an exploratory single-arm proof of concept Phase IIa study
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    13 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Baricitinib active treatment
    Arm Type
    Experimental
    Arm Description
    Baricitinib 4 mg/day
    Intervention Type
    Drug
    Intervention Name(s)
    Baricitinib
    Other Intervention Name(s)
    Olumiant
    Intervention Description
    4 mg/day for 7 days
    Primary Outcome Measure Information:
    Title
    Response to treatment: absence of moderate to severe oxygenation impairment (Berlin criteria)
    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)
    Time Frame
    8 days
    Title
    Response to treatment: survival
    Description
    Absence of death within 8 days from enrollment
    Time Frame
    8 days
    Secondary Outcome Measure Information:
    Title
    To quantify the rate of each of: moderate or severe oxygenation impairment within 8 days
    Description
    Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)
    Time Frame
    8 days
    Title
    To quantify the rate of each of: moderate or severe oxygenation impairment within 15 days
    Description
    Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)
    Time Frame
    15 days
    Title
    Mortality
    Description
    To quantify mortality within 8 and 15 days
    Time Frame
    8 days and 15 days
    Title
    Peripheral capillary oxygen saturation (SpO2)
    Description
    SpO2 will be assessed with the median and 25th-75th percentiles
    Time Frame
    8 days; 15 days
    Title
    Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2)
    Description
    PaO2/FiO2 will be assessed with the median and 25th-75th percentiles
    Time Frame
    8 days; 15 days
    Title
    To assess the rate of patients admitted to the intensive care unit
    Description
    Number of patients over the number of patients enrolled
    Time Frame
    8 days; 15 days
    Title
    To measure the length of hospital stay
    Description
    Median number of days and 25th-75th percentiles
    Time Frame
    8 days; 15 days
    Title
    28-day mortality
    Description
    To quantify 28-day mortality
    Time Frame
    28 days
    Title
    To quantify the rate of re-admission within 28 days
    Description
    Number of patients readmitted over the number patients enrolled
    Time Frame
    28 days
    Title
    To quantify the cumulative incidence and severity of adverse events
    Description
    Number, type, and severity of adverse events
    Time Frame
    28 days
    Title
    Interleukin (IL)-1; IL-2; IL-10; IL-6; IL-8; IL-17; IL-2 receptor levels;
    Description
    Serial serum assessments from baseline up to 15 days
    Time Frame
    15 days
    Title
    TNFalpha; vascular endothelial growth factor (VEGF); interferon gamma (IFNgamma) levels
    Description
    Serial serum assessments from baseline up to 15 days
    Time Frame
    15 days
    Title
    Viral load analyses
    Description
    Serial assessments from baseline up to 15 days for viral load persistence
    Time Frame
    15 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    74 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Ability to obtain informed patient consent noting the limitations of existing knowledge regarding Baricitinib's efficacy and the labeled warning and precautions as the proposed use is outside the approved indication, as well as the presence of known risk of being treated with Baricitinib while the subject of an active infection informed Consent as documented by signature patients with a confirmed SARS-CoV-2 pneumonia adult patients aged 18-74 years old infiltrates at chest radiography c-reactive protein level greater than 10 mg/dl or ferritin level > 900 ug/L Lymphocyte count less than 1500/mmc > 200 PaO2/FiO2 ≤ 300 Exclusion Criteria: patients aged < 18 years old and ≥ 75 years old concomitant bacterial infection lymphopenia less than 500/mmc hemoglobin < 8 g/dl absolute neutrophil count < 1 x 109 cells/L requiring continuous positive airway pressure (C-PAP) or mechanical ventilation sudden clinical deterioration requiring intensive care unit access known hypersensitivity or allergy to the study drug Creatinine clearance < 30 mL/min; if the creatinine clearance is between 30 and 60 mL/min the dose of Baricitinib should be reduced to 2 mg/daily Severe hepatic impairment (no dose adjustment of Baricitinib is required in mild or moderate hepatic impairment) Pregnant or breast-feeding Active tuberculosis Evidence of active hepatitis B (HBV) (HbsAg positive) or with detectable hepatitis C virus (HCV)-RNA, human immunodeficiency virus (HIV) Ongoing, acute diagnosis of deep venous thrombosis/pulmonary embolism (DVT/PE) Previous diagnosis of DVT/PE
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Sara Monti, MD
    Phone
    0382501878
    Email
    sara.saramonti@gmail.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Valentina Zuccaro, MD
    Phone
    0382501080
    Email
    V.Zuccaro@smatteo.pv.it
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Carlomaurizio Montecucco, Prof
    Organizational Affiliation
    Rheumatology, IRCCS Fondazione Policlinico S. Matteo, Pavia, Italy
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    Raffaele Bruno, Prof
    Organizational Affiliation
    Infectious Diseases; IRCCS Fondazione Policlinico S. Matteo, Pavia, Italy
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    32032529
    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.
    Results Reference
    background
    PubMed Identifier
    32113509
    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.
    Results Reference
    background

    Learn more about this trial

    Baricitinib for coRona Virus pnEumonia (COVID-19): a THerapeutic Trial

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