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COVID-19 Ozanimod Intervention Study (COZI)

Primary Purpose

COVID-19

Status

Terminated

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Ozanimod

Standard of care

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring S1P1 ligand, SARS-CoV-2, Oxygen requirement, WHO-adapted 6-points ordinal scale

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 40
Patients with hypoxemia related to viral pneumonia (COVID-19) requiring oxygen or nasal high flow therapy (to maintain SpO2 above 92%) without criteria for immediate intubation or need for other respiratory supports (CPAP, non-invasive ventilation).
Initiation of oxygen supplementation < 72 hours
eGFR (CKD EPI) > 30 ml/min/1.73m2
Serum troponin i < 80 ng/L
Heart rate ≥ 55 bpm if beta blockers or calcium channel blocker nondihydropyridine are used, and ≥ 60 bpm in the other patients

Exclusion criteria Medical conditions

Level of care B (unless patient agrees to intubation at study enrollment), C or D (patient admitted for palliative care; or physician is not committed to life-sustaining therapies)
No SpO2 signal available (only if FreeO2 apparatus is used)
Patient agitation (only if FreeO2 apparatus is used)
Severe untreated 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
Persistent hypotension.

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 or chronic use of corticosteroid (> 7.5 mg per day more than 3 months)
Receiving Class Ia and class III anti-arrythmic drugs amiodarone, sotalol, flecainide, propafenone
Patients receiving or anticipated to receive hydroxychloroquine or azithromycin.

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

Other exclusions

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

Sites / Locations

Hôpital de la Cité-de-la-Santé (CISSS de Laval)
Hôpital Santa Cabrini Ospedale (CIUSSS EMTL)
Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Ozanimod + standard of care

Standard of care

Arm Description

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.).

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).

Outcomes

Primary Outcome Measures

Daily Patient progression assessed with the World Health Organization-adapted 6-points ordinal scale

Clinical improvement until hospital discharge

Secondary Outcome Measures

The mean oxygen flow required to maintain the oxygen saturation (SpO2) target at 92%

Titrated every second with automated oxygen titration device (FreeO2)

Rate of non invasive ventilation (NIV) / high flow nasal therapy (HFNT) use

Rate of intubation

Ventilator-free and oxygen-free days at day 28

Rate of ICU admission/length of stay/mortality

Severity index measurement

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

Full Information

NCT ID

NCT04405102

First Posted

May 26, 2020

Last Updated

May 13, 2022

Sponsor

Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Collaborators

Celgene, Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT04405102

Brief Title

COVID-19 Ozanimod Intervention Study

Acronym

COZI

Official Title

A Randomized Trial on Efficacy and Safety of Ozanimod for the Treatment of COVID-19 Patients Requiring Oxygen Support - A Pilot Trial

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Terminated

Why Stopped

Screening was stopped by the Sponsor (43/48 participants enrolled), given the very low number of eligible patients (high vaccination rate and occurrence of the Omicron variant). The last patient randomized performed his follow-up visit.

Study Start Date

September 16, 2020 (Actual)

Primary Completion Date

March 14, 2022 (Actual)

Study Completion Date

May 12, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Collaborators

Celgene, Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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 preclinical models, 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, and was recently (October 2020) approved by Health Canada for the same indication. 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.

6. Conditions and Keywords

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

COVID-19

Keywords

S1P1 ligand, SARS-CoV-2, Oxygen requirement, WHO-adapted 6-points ordinal scale

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

43 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ozanimod + standard of care

Arm Type

Experimental

Arm Description

Arm Title

Standard of care

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Ozanimod

Other Intervention Name(s)

Zeposia (USA)

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Standard of care

Intervention Description

Primary Outcome Measure Information:

Title

Daily Patient progression assessed with the World Health Organization-adapted 6-points ordinal scale

Description

Clinical improvement until hospital discharge

Time Frame

through whole duration of the hospitalization, an average of 14 days

Secondary Outcome Measure Information:

Title

The mean oxygen flow required to maintain the oxygen saturation (SpO2) target at 92%

Description

Titrated every second with automated oxygen titration device (FreeO2)

Time Frame

First 7 days of the trial

Title

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

Title

Rate of intubation

Time Frame

through whole duration of the hospitalization, an average of 14 days

Title

Ventilator-free and oxygen-free days at day 28

Time Frame

through whole duration of the hospitalization, an average of 14 days

Title

Rate of ICU admission/length of stay/mortality

Time Frame

through whole duration of the hospitalization, an average of 14 days

Title

Severity index measurement

Description

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

Time Frame

through whole duration of the hospitalization, an average of 14 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 40 Patients with hypoxemia related to viral pneumonia (COVID-19) requiring oxygen or nasal high flow therapy (to maintain SpO2 above 92%) without criteria for immediate intubation or need for other respiratory supports (CPAP, non-invasive ventilation). Initiation of oxygen supplementation < 72 hours eGFR (CKD EPI) > 30 ml/min/1.73m2 Serum troponin i < 80 ng/L Heart rate ≥ 55 bpm if beta blockers or calcium channel blocker nondihydropyridine are used, and ≥ 60 bpm in the other patients Exclusion criteria Medical conditions Level of care B (unless patient agrees to intubation at study enrollment), C or D (patient admitted for palliative care; or physician is not committed to life-sustaining therapies) No SpO2 signal available (only if FreeO2 apparatus is used) Patient agitation (only if FreeO2 apparatus is used) Severe untreated 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 Persistent hypotension. 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 or chronic use of corticosteroid (> 7.5 mg per day more than 3 months) Receiving Class Ia and class III anti-arrythmic drugs amiodarone, sotalol, flecainide, propafenone Patients receiving or anticipated to receive hydroxychloroquine or azithromycin. Prior/concurrent clinical study experience -Current enrolment in an interventional arm of a clinical trial with similar endpoints to the COZI trial Other exclusions -Patients or legal/authorized representatives who refuse to participate to the study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

François Lellouche, MD

Organizational Affiliation

IUCPQ-UL

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

David Marsolais, PhD

Organizational Affiliation

CRIUCPQ-UL

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Nathalie Châteauvert, B. pharm

Organizational Affiliation

CRIUCPQ-UL

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Pascale Blais-Lecours, PhD

Organizational Affiliation

CRIUCPQ-UL

Official's Role

Study Director

Facility Information:

Facility Name

Hôpital de la Cité-de-la-Santé (CISSS de Laval)

City

Laval

State/Province

Quebec

ZIP/Postal Code

H7M 3L9

Country

Canada

Facility Name

Hôpital Santa Cabrini Ospedale (CIUSSS EMTL)

City

Montréal

State/Province

Quebec

ZIP/Postal Code

H1T 1P7

Country

Canada

Facility Name

Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval

City

Québec

ZIP/Postal Code

G1V 4G5

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

COVID-19 Ozanimod Intervention Study

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