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COVID-19 Ozanimod Intervention Study (COZI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04405102
Recruitment Status : Recruiting
First Posted : May 28, 2020
Last Update Posted : September 30, 2020
Sponsor:
Collaborators:
Celgene
Bristol-Myers Squibb
Information provided by (Responsible Party):
François Lellouche, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Tracking Information
First Submitted Date  ICMJE May 26, 2020
First Posted Date  ICMJE May 28, 2020
Last Update Posted Date September 30, 2020
Actual Study Start Date  ICMJE September 16, 2020
Estimated Primary Completion Date January 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 4, 2020)
Daily Patient progression assessed with the World Health Organization-adapted 6-points ordinal scale [ Time Frame: through whole duration of the hospitalization, an average of 14 days ]
Clinical improvement until hospital discharge
Original Primary Outcome Measures  ICMJE
 (submitted: May 26, 2020)
  • The mean oxygen flow required to maintain the oxygen saturation (SpO2) target at 92% [ Time Frame: First 7 days of the trial ]
    Titrated every second with automated oxygen titration device (FreeO2)
  • Daily Patient progression assessed with the World Health Organization-adapted 6-points ordinal scale [ Time Frame: through whole duration of the hospitalization, an average of 14 days ]
    Clinical improvement until hospital discharge
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 4, 2020)
  • The mean oxygen flow required to maintain the oxygen saturation (SpO2) target at 92% [ Time Frame: First 7 days of the trial ]
    Titrated every second with automated oxygen titration device (FreeO2)
  • Rate of non invasive ventilation (NIV) / high flow nasal therapy (HFNT) use [ Time Frame: through whole duration of the hospitalization, an average of 14 days ]
  • Rate of intubation [ Time Frame: through whole duration of the hospitalization, an average of 14 days ]
  • Ventilator-free days at day 28 [ Time Frame: through whole duration of the hospitalization, an average of 14 days ]
  • Rate of ICU admission/length of stay/mortality [ Time Frame: through whole duration of the hospitalization, an average of 14 days ]
  • Severity index measurement [ Time Frame: through whole duration of the hospitalization, an average of 14 days ]
    Sepsis-related organ failure assessment (SOFA), national early warning score (NEWS2), early warning score for oxygen therapy (EWS.O2), decrease of at least 2 points on the 6-point ordinal scale
Original Secondary Outcome Measures  ICMJE
 (submitted: May 26, 2020)
  • Rate of non invasive ventilation (NIV) / high flow nasal therapy (HFNT) use [ Time Frame: through whole duration of the hospitalization, an average of 14 days ]
  • Rate of intubation [ Time Frame: through whole duration of the hospitalization, an average of 14 days ]
  • Ventilator-free days at day 28 [ Time Frame: through whole duration of the hospitalization, an average of 14 days ]
  • Rate of ICU admission/length of stay/mortality [ Time Frame: through whole duration of the hospitalization, an average of 14 days ]
  • Severity index measurement [ Time Frame: through whole duration of the hospitalization, an average of 14 days ]
    Sepsis-related organ failure assessment (SOFA), national early warning score (NEWS2), early warning score for oxygen therapy (EWS.O2), decrease of at least 2 points on the 6-point ordinal scale
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE COVID-19 Ozanimod Intervention Study
Official Title  ICMJE A Randomized Trial on Efficacy and Safety of Ozanimod for the Treatment of COVID-19 Patients Requiring Oxygen Support - A Pilot Trial
Brief Summary

The virus SARS-CoV-2 causes severe pneumonia which, in a proportion of patients progresses towards an Acute Respiratory Distress Syndrome (ARDS) mainly related to the antiviral immune response. To date, there is no available treatment that significantly improves outcome of patients with COVID-19 pneumonia. Sphingosine-1-phosphate receptor 1 (S1P1) ligands control vascular leakage in the airways and sphingosine-1-phosphate (S1P) receptor ligands devoid of activity on sphingosine-1-phosphate receptor 3 (S1P3) show an excellent safety profile, including ozanimod. Critically, S1P1 ligands mildly impact, but do not compromise viral clearance and they reduced lung injury in the highly pathogenic H1N1-ferret model, even without concomitant use of antivirals and with a synergistic effect when associated to antiviral agents. Ozanimod was approved by the FDA for the treatment of relapsing multiple sclerosis at the end of March 2020. The investigators believe that this immune modulator is at the top of the list of agents that should be trialed in order to mitigate the morbidity and mortality of COVID-19.

The primary objective is to substantiate the impact of ozanimod on key outcomes of COVID-19 patient progression, which will guide decision making around sample size and the choice of endpoints for future clinical trial.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE
  • Drug: Ozanimod
    The investigational medical product (IMP) for this study is ozanimod. Ozanimod 0.23 mg be administered once daily for 4 days and then ozanimod 0.46 mg will be administered once daily for ten days.
    Other Name: Zeposia (USA)
  • Other: Standard of care
    During hospitalization, patient will be given standard of care (Recommendations for standard of care management of COVID-19 will be provided for anticoagulation, fluid resuscitation, corticoids and other immunomodulators, antipyretics agents, antiviral agents and other treatments. These recommendations are subject to modifications based on the new literature data).
Study Arms  ICMJE
  • Experimental: Ozanimod + standard of care
    During hospitalization, the experiment treatment of Ozanimod will be given with the standard of care (Recommendations for standard of care management of COVID-19 will be provided for anticoagulation, fluid resuscitation, corticoids and other immunomodulators, antipyretics agents, antiviral agents and other treatments. These recommendations are subject to modifications based on the new literature data.).
    Interventions:
    • Drug: Ozanimod
    • Other: Standard of care
  • Active Comparator: Standard of care
    During hospitalization, patient will be given standard of care (Recommendations for standard of care management of COVID-19 will be provided for anticoagulation, fluid resuscitation, corticoids and other immunomodulators, antipyretics agents, antiviral agents and other treatments. These recommendations are subject to modifications based on the new literature data).
    Intervention: Other: Standard of care
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 26, 2020)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 1, 2024
Estimated Primary Completion Date January 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria

  • Confirmed COVID-19 (positive polymerase chain reaction (PCR) for COVID-19 from any specimen)
  • Patients older than 18 years old and younger than 85 years old.
  • BMI higher than 20 but lower than 35
  • Patients with hypoxemia related to viral pneumonia (COVID-19) requiring oxygen therapy below 6 L/min (or fraction of inspired oxygen (FiO2) < 0.50) (to maintain SpO2 above 92%) without criteria for immediate intubation or need for other respiratory supports (CPAP, non-invasive ventilation of high flow nasal therapy).
  • Patients hospital admission < 72 hours
  • Serum creatinine < 124 μmol/L
  • Serum troponin < 28 ng/L

Exclusion criteria Medical conditions

  • Level of care B, C or D (patient admitted for palliative care; or physician is not committed to life-sustaining therapies)
  • No SpO2 signal available
  • Patient agitation
  • Severe sleep apnea
  • History of or currently active primary or secondary immunodeficiency
  • Recent (within the last 6 months) occurrence of myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, class III/IV heart failure
  • Known presence of Mobitz type II second-degree or third-degree atrioventricular block, sick sinus syndrome, or sinoatrial block, unless patient has a functioning pacemaker
  • Child-Pugh score class C
  • Pregnancy, lactation, or a positive serum beta human chorionic gonadotropin measured during screening.

Prior/concomitant therapy

  • Receipt of a live vaccine within 4 weeks prior to randomization
  • Receiving MAO inhibitor (tranylcypromine, selegiline or phenelzine)
  • Receiving pharmacological treatment for a form of multiple sclerosis
  • Use of long-term immunosuppressors (Ex. tacrolimus, cyclosporin, azathioprine, mycophenolate, sirolimus, methotrexate; and chronic use of corticosteroid (> 7.5 mg per day more than 3 months)
  • Receiving Class 1a and class III anti-arrythmic drugs amiodarone, sotalol, flecainide, propafenone
  • Patients receiving or anticipated to receive chloroquine or azithromycin.

Prior/concurrent clinical study experience -Current enrolment in a clinical trial with similar endpoints to the COZI trial

Other exclusions

-Patients or legal/authorized representatives who refuse to participate to the study.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pascale Blais-Lecours, PhD 418-656-8711 ext 2651 pascale.blais-lecours@criucpq.ulaval.ca
Contact: David Marsolais, PhD 418-656-8711 ext 3085 david.marsolais@criucpq.ulaval.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04405102
Other Study ID Numbers  ICMJE 2021-3474
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party François Lellouche, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
Study Sponsor  ICMJE Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
Collaborators  ICMJE
  • Celgene
  • Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: François Lellouche, MD IUCPQ-UL
Study Chair: David Marsolais, PhD CRIUCPQ-UL
Study Chair: Nathalie Châteauvert, B. pharm CRIUCPQ-UL
Study Director: Pascale Blais-Lecours, PhD CRIUCPQ-UL
PRS Account Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP