COVID-19 Ozanimod Intervention Study

NCT04405102 | Terminated Phase 2 DMC

• 1 other identifier: 2021-3474
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 3

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.

Conditions

COVID-19

Keywords

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

Outcome Measures

Primary Outcomes (1)

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

  Clinical improvement until hospital discharge

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

Secondary Outcomes (6)

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

  First 7 days of the trial

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

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

• Rate of intubation

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

• Ventilator-free and oxygen-free days at day 28

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

• Rate of ICU admission/length of stay/mortality

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

Study Arms (2)

Ozanimod + standard of care

EXPERIMENTAL

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.).

Drug: Ozanimod; Other: Standard of care

Standard of care

ACTIVE COMPARATOR

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).

Other: Standard of care

Interventions

Ozanimod DRUG

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.

Also known as: Zeposia (USA)

Ozanimod + standard of care

Standard of care OTHER

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).

Ozanimod + standard of care; Standard of care

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec: lead
• Celgene: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (3)

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

Laval, Quebec, H7M 3L9, Canada

Location

Hôpital Santa Cabrini Ospedale (CIUSSS EMTL)

Montreal, Quebec, H1T 1P7, Canada

Location

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

Québec, G1V 4G5, Canada

Location

Related Publications (1)

• Lellouche F, Blais-Lecours P, Maltais F, Sarrazin JF, Rola P, Nguyen T, Chateauvert N, Marsolais D. Ozanimod Therapy in Patients With COVID-19 Requiring Oxygen Support: A Randomized Open-Label Pilot Trial. Chest. 2024 Apr;165(4):810-819. doi: 10.1016/j.chest.2023.10.023. Epub 2023 Oct 28.

  PMID: 37898184 RESULT

MeSH Terms

Conditions

COVID-19

Interventions

ozanimod; Standard of Care

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• François Lellouche, MD

  IUCPQ-UL

  PRINCIPAL INVESTIGATOR

• David Marsolais, PhD

  CRIUCPQ-UL

  STUDY CHAIR

• Nathalie Châteauvert, B. pharm

  CRIUCPQ-UL

  STUDY CHAIR

• Pascale Blais-Lecours, PhD

  CRIUCPQ-UL

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: May 26, 2020
• First Posted: May 28, 2020
• Study Start: September 16, 2020
• Primary Completion: March 14, 2022
• Study Completion: May 12, 2022
• Last Updated: February 20, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)