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

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)

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.

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Drug: Placebo; Drug: Ruxolitinib

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: Phase 3

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation, 198205
    • Sbih City Hospital 15
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Honor Health Research Institute
  • California
    • San Diego, California, United States, 92123
      • Sharp Memorial Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
  • Florida
    • Brandon, Florida, United States, 33511
      • Teradan Clinical Trials
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
    • Tampa, Florida, United States, 33613
      • University of South Florida
  • Illinois
    • Chicago, Illinois, United States, 60678
      • NorthShore University Health System
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Simon Cancer Center
    • Indianapolis, Indiana, United States, 46219
      • Indiana University Health Central Indiana Cancer Centers
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • East Jefferson General Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital & Medical Center
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Medical School
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • HealthPartners Cancer Care Center - Regions Hospital
  • Missouri
    • Springfield, Missouri, United States, 65804
      • Mercy Research
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Newark, New Jersey, United States, 07103
      • Rutgers Njms Clinical Research Unit
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Greenville, North Carolina, United States, 27858
      • East Carolina University
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Dayton, Ohio, United States, 45429
      • Kettering Cancer Care
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
    • Philadelphia, Pennsylvania, United States, 19107
      • Jefferson University Hospitals
    • Pittsburgh, Pennsylvania, United States, 15224
      • West Penn Hospital
    • Wexford, Pennsylvania, United States, 15090
      • Allegheny Health Network
  • Texas
    • Austin, Texas, United States, 78705
      • St David's Medical Center
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center At Houston - McGovern Medical School
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Cente
  • Washington
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital and Clinics
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53233
      • Aurora Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Placebo; Placebo administered BID approximately 12 hours apart
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.	Drug: Ruxolitinib; Ruxolitinb administered BID approximately 12 hours apart; Other Names: INCB018424; Oral Jak Inhibitor
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.	Drug: Ruxolitinib; Ruxolitinb administered BID approximately 12 hours apart; Other Names: INCB018424; Oral Jak Inhibitor

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Incyte Corporation

Publications and helpful links

General Publications

• Rein L, Calero K, Shah R, Ojielo C, Hudock KM, Lodhi S, Sadaka F, Bellam S, Palma C, Hager DN, Daniel J, Schaub R, O'Hayer K, Theodoropoulos NM. Randomized Phase 3 Trial of Ruxolitinib for COVID-19-Associated Acute Respiratory Distress Syndrome. Crit Care Med. 2022 Dec 1;50(12):1701-1713. doi: 10.1097/CCM.0000000000005682. Epub 2022 Oct 13.

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2020
• Primary Completion (Actual): February 26, 2021
• Study Completion (Actual): February 26, 2021

Study Registration Dates

• First Submitted: May 4, 2020
• First Submitted That Met QC Criteria: May 4, 2020
• First Posted (Actual): May 6, 2020

Study Record Updates

• Last Update Posted (Actual): January 19, 2022
• Last Update Submitted That Met QC Criteria: January 14, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; ARDS; pneumonia; Cytokine storm; ruxolitinib
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Janus Kinase Inhibitors
• Other Study ID Numbers: INCB 18424-369

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No