Assessment of Efficacy and Safety of Ruxolitinib in Participants With COVID-19-Associated ARDS Who Require Mechanical Ventilation (RUXCOVID-DEVENT)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of ruxolitinib in the treatment of participants with COVID-19-associated Acute Respiratory Distress Syndrome (ARDS) who require mechanical ventilation.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Efficacy and Safety of Ruxolitinib in Participants With COVID-19-Associated ARDS Who Require Mechanical Ventilation (RUXCOVID-DEVENT)

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Placebo
* Drug: Ruxolitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant or guardian health proxy must provide informed consent before any study assessment is performed. Male or female participants aged ≥ 12 years. Participants with coronavirus (SARS-CoV-2) infection confirmed ≤ 3 weeks prior to randomization by any test with local regulatory approval. Participants who are intubated and receiving mechanical ventilation due to COVID-19-associated ARDS and have a PaO2/FiO2 of ≤ 300 mmHg within 6 -hours of randomization. Participants with lung imaging showing bilateral or diffuse pulmonary infiltrates on chest x-ray or CT scan. Exclusion Criteria: Known history of hypersensitivity to any drugs or metabolites of similar chemical classes as ruxolitinib. Presence of severely impaired renal function defined by estimated creatinine clearance < 15 mL/min measured or calculated by Cockcroft-Gault equation or calculated by the updated bedside Schwartz equation. Participants must not be receiving CRRT or intermittent hemodialysis at screening. In the opinion of the investigator, unlikely to survive for > 24 hours from randomization. Suspected active uncontrolled bacterial, fungal, viral, or other infection (besides COVID-19). Currently receiving ECMO. Participant may not be sharing a ventilator, or co-ventilating, with any other patient. Treatment with anti-IL-6, IL-6R, IL-1RA, IL-1β, or GM-CSF antagonists, or a BTK inhibitor, within 7 days of randomization. Treatment with a JAK inhibitor within 30 days of randomization. Participants who are on long-term use of antirejection or immunomodulatory drugs. Pregnant or nursing (lactating) women.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo + Standard of Care (SoC)<br>Matching Placebo will be administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral. | Drug: Placebo<br>* Placebo administered BID approximately 12 hours apart<br>|
| Experimental: Ruxolitinib 5mg + Standard of Care (SoC)<br>Ruxolitinib 5mg will be administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral. | Drug: Ruxolitinib<br>* Ruxolitinb administered BID approximately 12 hours apart<br>* Other names: Oral Jak Inhibitor;|
| Experimental: Ruxolitininb 15mg + Standard of Care (SoC)<br>Ruxolitinib 15mg will be administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral. | Drug: Ruxolitinib<br>* Ruxolitinb administered BID approximately 12 hours apart<br>* Other names: Oral Jak Inhibitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Have Died Due to Any Cause | To evaluate the 28-day mortality rate of ruxolitinib 5 mg BID + SoC therapy and ruxolitinib 15 mg BID + SoC compared with placebo + SoC therapy, in participants with COVID-19-associated ARDS who require mechanical ventilation. | Study start to Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Ventilator Free Days | Number of days participant did not require mechanical ventilation | Study start to Day 29 | 
| Number of ICU Free Days | Number of days participant is out of the ICU | Study start to Day 29 | 
| Oxygen Free Days | Number of days participant did not receive supplemental oxygen | Study start to Day 29 | 
| Vasopressor Free Days | Number of days without use of vasopressor therapy | Study start to Day 29 | 
| Hospital Free Days | Number of days Partcipant is out of the hospital | Study start to Day 29 | 
| Percentage of Participants With at Least 2-point Improvement in the COVID-19 Ordinal Scale | Participants with at least 2-point improvement at Day 15 and 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead | Study start to Days 15 and 29 | 
| Percentage of Participants With at Least 1-point Improvement in the COVID-19 Ordinal Scale | Participants with at lest 1-point improvement in clinical status at Days 15 and 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead | Study start to Days 15 and 29 | 
| Time to Improvement From Baseline Category to Earliest 1-point Improvement in the COVID-19 Ordinal Scale | TIme to improvement compared to baseline. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead | Study Start to Day 29 | 
| Percentage of Participants With the COVID-19 Ordinal Scale Reported | Clinical status of participant at Day 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead | Study start to Day 29 | 
| Change in the COVID-19 9-point Ordinal Scale | Change in the Clinical status of participant at Days 15 and 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead | Study start to Days 15 and 29 | 
| Change in SOFA Score | Sequential Organ Failure Assessment (SOFA) score is a scoring system to determine the extent of a person's organ function or rate of failure. The score is based on 6 different scores, 1 each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each system gets a score from 0 (normal) to 4 (abnormal) and the sum of each score defines the final SOFA score, which 24 is the maximum score (high risk of morality) and 0 is the minimum score (low risk of mortality). | from baseline to Days 3, 5, 8, 11, 15, and 29 | 
| Number and Percentage of Participants With Treatment-related Side Effects and Serious Adverse Events | Treatment-emergent AEs are judged as related by the investigator or have a missing causality. | Study start to Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cytokine storm, COVID-19, ARDS, SARS-CoV-2, ruxolitinib, pneumonia