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

• ClinicalTrials.gov Identifier: NCT04377620
• Recruitment Status: Terminated
• First Posted: May 6, 2020
• Results First Posted: January 19, 2022
• Last Update Posted: January 19, 2022
• Sponsor: Incyte Corporation
• Information provided by (Responsible Party): Incyte Corporation

Tracking Information

• First Submitted Date: May 4, 2020
• First Posted Date: May 6, 2020
• Results First Submitted Date: November 17, 2021
• Results First Posted Date: January 19, 2022
• Last Update Posted Date: January 19, 2022
• Actual Study Start Date: May 24, 2020
• Actual Primary Completion Date: February 26, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 15, 2021)

Percentage of Participants Who Have Died Due to Any Cause [ Time Frame: Study start to Day 29 ]

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.

Original Primary Outcome Measures (submitted: May 4, 2020)

Proportion of participants who have died due to any cause [ Time Frame: Up to Day 29 ]

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.

Current Secondary Outcome Measures (submitted: December 15, 2021)

• Number of Ventilator Free Days [ Time Frame: Study start to Day 29 ]
  Number of days participant did not require mechanical ventilation
• Number of ICU Free Days [ Time Frame: Study start to Day 29 ]
  Number of days participant is out of the ICU
• Oxygen Free Days [ Time Frame: Study start to Day 29 ]
  Number of days participant did not receive supplemental oxygen
• Vasopressor Free Days [ Time Frame: Study start to Day 29 ]
  Number of days without use of vasopressor therapy
• Hospital Free Days [ Time Frame: Study start to Day 29 ]
  Number of days Partcipant is out of the hospital
• Percentage of Participants With at Least 2-point Improvement in the COVID-19 Ordinal Scale [ Time Frame: Study start to Days 15 and 29 ]
  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
• Percentage of Participants With at Least 1-point Improvement in the COVID-19 Ordinal Scale [ Time Frame: Study start to Days 15 and 29 ]
  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
• Time to Improvement From Baseline Category to Earliest 1-point Improvement in the COVID-19 Ordinal Scale [ Time Frame: Study Start to Day 29 ]
  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
• Percentage of Participants With the COVID-19 Ordinal Scale Reported [ Time Frame: Study start to Day 29 ]
  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
• Change in the COVID-19 9-point Ordinal Scale [ Time Frame: Study start to Days 15 and 29 ]
  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
• Change in SOFA Score [ Time Frame: from baseline to Days 3, 5, 8, 11, 15, and 29 ]
  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).
• Number and Percentage of Participants With Treatment-related Side Effects and Serious Adverse Events [ Time Frame: Study start to Day 29 ]
  Treatment-emergent AEs are judged as related by the investigator or have a missing causality.

Original Secondary Outcome Measures (submitted: May 4, 2020)

• Number of Ventilator free days [ Time Frame: Day 29 ]
  Number of days participant did not require mechanical ventilation
• Number of ICU free days [ Time Frame: Day 29 ]
  Number of days participant is out of the ICU
• Oxygen free days [ Time Frame: Day 29 ]
  Number of days participant did not receive supplemental oxygen
• Vasopressor free days [ Time Frame: Day 29 ]
  Number of days without use of vasopressor therapy
• Hospital free days [ Time Frame: Day 29 ]
  Number of days Partcipant is out of the hospital
• Improvement in the COVID-19 ordinal scale [ Time Frame: Day 15 and 29 ]
  Clinical status of participant 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
• Change in SOFA Score [ Time Frame: from baseline to Days 3, 5, 8, 11, 15, and 29 ]
  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.
• Number of treatment-related adverse events [ Time Frame: Day 29 ]
  Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Assessment of Efficacy and Safety of Ruxolitinib in Participants With COVID-19-Associated ARDS Who Require Mechanical Ventilation (RUXCOVID-DEVENT)
• Official Title: 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)
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:

Double blinded

Primary Purpose: Treatment

• Condition: COVID-19

Intervention

• Drug: Placebo
  Placebo administered BID approximately 12 hours apart
• Drug: Ruxolitinib
  Ruxolitinb administered BID approximately 12 hours apart
  Other Names:

  • INCB018424
  • Oral Jak Inhibitor

Study Arms

• Placebo Comparator: Placebo + Standard of Care (SoC)
  Matching Placebo will be administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
  Intervention: Drug: Placebo
• Experimental: Ruxolitinib 5mg + Standard of Care (SoC)
  Ruxolitinib 5mg will be administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
  Intervention: Drug: Ruxolitinib
• Experimental: Ruxolitininb 15mg + Standard of Care (SoC)
  Ruxolitinib 15mg will be administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
  Intervention: Drug: Ruxolitinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 11, 2021): 211
• Original Estimated Enrollment (submitted: May 4, 2020): 500
• Actual Study Completion Date: February 26, 2021
• Actual Primary Completion Date: February 26, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Russian Federation, United States

Administrative Information

• NCT Number: NCT04377620
• Other Study ID Numbers: INCB 18424-369
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Incyte Corporation
• Original Responsible Party: Same as current
• Current Study Sponsor: Incyte Corporation
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Incyte Corporation
• Verification Date: January 2022