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

• Sponsor: Incyte Corporation (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT04377620
• Collaborator: (none)
• Enrollment: 211
• Locations: 36
• Arms: 3
• Actual Duration (Months): 9.1
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: Placebo; Drug: Ruxolitinib	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 211 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Double blinded
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: May 24, 2020
• Actual Primary Completion Date: Feb 26, 2021
• Actual Study Completion Date: Feb 26, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Have Died Due to Any Cause [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.

Secondary Outcome Measures

1. Number of Ventilator Free Days [Study start to Day 29]

   Number of days participant did not require mechanical ventilation

2. Number of ICU Free Days [Study start to Day 29]

   Number of days participant is out of the ICU

3. Oxygen Free Days [Study start to Day 29]

   Number of days participant did not receive supplemental oxygen

4. Vasopressor Free Days [Study start to Day 29]

   Number of days without use of vasopressor therapy

5. Hospital Free Days [Study start to Day 29]

   Number of days Partcipant is out of the hospital

6. Percentage of Participants With at Least 2-point Improvement in the COVID-19 Ordinal Scale [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

7. Percentage of Participants With at Least 1-point Improvement in the COVID-19 Ordinal Scale [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

8. Time to Improvement From Baseline Category to Earliest 1-point Improvement in the COVID-19 Ordinal Scale [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

9. Percentage of Participants With the COVID-19 Ordinal Scale Reported [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

10. Change in the COVID-19 9-point Ordinal Scale [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

11. Change in SOFA Score [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).

12. Number and Percentage of Participants With Treatment-related Side Effects and Serious Adverse Events [Study start to Day 29]

    Treatment-emergent AEs are judged as related by the investigator or have a missing causality.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Honor Health Research Institute	Scottsdale	Arizona	United States	85258
2	Sharp Memorial Hospital	San Diego	California	United States	92123
3	Georgetown University Hospital	Washington	District of Columbia	United States	20007
4	Teradan Clinical Trials	Brandon	Florida	United States	33511
5	University of Florida	Gainesville	Florida	United States	32610
6	Tampa General Hospital	Tampa	Florida	United States	33606
7	University of South Florida	Tampa	Florida	United States	33613
8	Northshore University Health System	Chicago	Illinois	United States	60678
9	Loyola University Medical Center	Maywood	Illinois	United States	60153
10	Indiana University Simon Cancer Center	Indianapolis	Indiana	United States	46202
11	Indiana University Health Central Indiana Cancer Centers	Indianapolis	Indiana	United States	46219
12	East Jefferson General Hospital	Metairie	Louisiana	United States	70006
13	Johns Hopkins University	Baltimore	Maryland	United States	21224
14	Boston Medical Center	Boston	Massachusetts	United States	02118
15	Lahey Hospital & Medical Center	Burlington	Massachusetts	United States	01805
16	University of Massachusetts Medical School	Worcester	Massachusetts	United States	01655
17	Healthpartners Cancer Care Center - Regions Hospital	Saint Paul	Minnesota	United States	55101
18	Mercy Research	Springfield	Missouri	United States	65804
19	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
20	Rutgers Njms Clinical Research Unit	Newark	New Jersey	United States	07103
21	Holy Name Medical Center	Teaneck	New Jersey	United States	07666
22	University of Rochester Medical Center	Rochester	New York	United States	14642
23	Duke University Medical Center	Durham	North Carolina	United States	27710
24	East Carolina University	Greenville	North Carolina	United States	27858
25	University of Cincinnati	Cincinnati	Ohio	United States	45219
26	Kettering Cancer Care	Dayton	Ohio	United States	45429
27	Jefferson University Hospitals	Philadelphia	Pennsylvania	United States	19107
28	Temple University	Philadelphia	Pennsylvania	United States	19140
29	West Penn Hospital	Pittsburgh	Pennsylvania	United States	15224
30	Allegheny Health Network	Wexford	Pennsylvania	United States	15090
31	St David'S Medical Center	Austin	Texas	United States	78705
32	University of Texas Health Science Center At Houston - McGovern Medical School	Houston	Texas	United States	77030
33	University of Texas Health Science Cente	San Antonio	Texas	United States	78229
34	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801
35	Aurora Research Institute	Milwaukee	Wisconsin	United States	53233
36	Sbih City Hospital 15	Saint Petersburg		Russian Federation	198205

Sponsors and Collaborators

• Incyte Corporation

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jun 2, 2020
• Statistical Analysis Plan - Feb 22, 2021

More Information

Publications

None provided.

• Responsible Party: Incyte Corporation
• ClinicalTrials.gov Identifier: NCT04377620
• Other Study ID Numbers: INCB 18424-369
• First Posted: May 6, 2020
• Last Update Posted: Jan 19, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Incyte Corporation: Cytokine storm; COVID-19; ARDS; SARS-CoV-2; ruxolitinib; pneumonia
• Additional relevant MeSH terms: COVID-19; Janus Kinase Inhibitors

Study Results

Participant Flow

Recruitment Details

This study was conducted at 33 study centers in the United States (29) and Russia (4), and 211 participants were enrolled and analyzed for efficacy.; 209 participants were analyzed for safety. Enrollment in this study was stopped early and was not due to safety reasons.

Pre-assignment Detail

Participants were randomly assigned in a 2:2:1 ratio to receive ruxolitinib 5 mg BID, ruxolitinib 15 mg BID, or placebo for an initial treatment period of 14 days; participants randomly assigned to receive placebo were randomly assigned in a 1:1 ratio to receive placebo matching ruxolitinib 5 mg BID or placebo matching ruxolitinib 15 mg BID. Randomization was stratified by ARDS severity (severe vs mild/moderate at the time of randomization) and investigative site.

Arm/Group Title	Ruxolitininb 15mg + Standard of Care	Ruxolitinib 5mg + Standard of Care (SoC)	Placebo + Standard of Care (SoC)
Arm/Group Description	Ruxolitinib 15mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Ruxolitinib 5mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Matching Placebo was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Period Title: Overall Study
STARTED	77	87	47
COMPLETED	35	37	11
NOT COMPLETED	42	50	36

Baseline Characteristics

Arm/Group Title	Ruxolitininb 15mg + Standard of Care (SoC)	Ruxolitinib 5mg + Standard of Care (SoC)	Placebo + Standard of Care (SoC)	Total
Arm/Group Description	Ruxolitinib 15mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Ruxolitinib 5mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Matching Placebo was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Total of all reporting groups
Overall Participants	77	87	47	211
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	63.6 (12.92)	63.6 (12.25)	62.5 (13.34)	63.4 (12.69)
Sex: Female, Male (Count of Participants)
Female	29 37.7%	32 36.8%	13 27.7%	74 35.1%
Male	48 62.3%	55 63.2%	34 72.3%	137 64.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	21 27.3%	21 24.1%	12 25.5%	54 25.6%
Not Hispanic or Latino	53 68.8%	64 73.6%	34 72.3%	151 71.6%
Unknown or Not Reported	3 3.9%	2 2.3%	1 2.1%	6 2.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	2 4.3%	2 0.9%
Asian	3 3.9%	3 3.4%	1 2.1%	7 3.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	9 11.7%	12 13.8%	5 10.6%	26 12.3%
White	57 74%	61 70.1%	31 66%	149 70.6%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	8 10.4%	11 12.6%	8 17%	27 12.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Have Died Due to Any Cause
Description	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.
Time Frame	Study start to Day 29

Outcome Measure Data

Analysis Population Description

ITT population is defined according to the treatment assignment at the time of randomization regardless of the actual study drug the participant might take during his/her participation in the study.

Arm/Group Title	Ruxolitininb 15mg + Standard of Care (SoC)	Ruxolitinib 5mg + Standard of Care (SoC)	Placebo + Standard of Care (SoC)
Arm/Group Description	Ruxolitinib 15mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Ruxolitinib 5mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Matching Placebo was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Measure Participants	77	85	47
Number [Percentage]	50.6	52.9	70.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ruxolitininb 15mg + Standard of Care (SoC)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0292
	Comments
	Method	Mixed Models Analysis
	Comments	logistic regression mixed model includes treatment group and ARDS severity as fixed covariates and investigational site as a random effect.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 95%; 0.201 to 1.028
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib 5mg + Standard of Care (SoC)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0280
	Comments
	Method	Mixed Models Analysis
	Comments	logistic regression mixed model includes treatment group and ARDS severity as fixed covariates and investigational site as a random effect.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.42
	Confidence Interval	(2-Sided) 95%; 0.171 to 1.023
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Ventilator Free Days
Description	Number of days participant did not require mechanical ventilation
Time Frame	Study start to Day 29

Outcome Measure Data

Analysis Population Description

ITT population is defined according to the treatment assignment at the time of randomization regardless of the actual study drug the participant might take during his/her participation in the study.

Arm/Group Title	Ruxolitininb 15mg + Standard of Care (SoC)	Ruxolitinib 5mg + Standard of Care (SoC)	Placebo + Standard of Care (SoC)
Arm/Group Description	Ruxolitinib 15mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Ruxolitinib 5mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Matching Placebo was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Measure Participants	77	85	47
Mean (Standard Deviation) [Days]	6.31 (9.047)	4.92 (8.398)	2.98 (7.228)

3. Secondary Outcome

Title	Number of ICU Free Days
Description	Number of days participant is out of the ICU
Time Frame	Study start to Day 29

Outcome Measure Data

Analysis Population Description

ITT population is defined according to the treatment assignment at the time of randomization regardless of the actual study drug the participant might take during his/her participation in the study.

Arm/Group Title	Ruxolitininb 15mg + Standard of Care (SoC)	Ruxolitinib 5mg + Standard of Care (SoC)	Placebo + Standard of Care (SoC)
Arm/Group Description	Ruxolitinib 15mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Ruxolitinib 5mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Matching Placebo was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Measure Participants	77	85	47
Mean (Standard Deviation) [Days]	4.75 (7.716)	4.00 (7.517)	2.45 (6.362)

4. Secondary Outcome

Title	Oxygen Free Days
Description	Number of days participant did not receive supplemental oxygen
Time Frame	Study start to Day 29

Outcome Measure Data

Analysis Population Description

ITT population is defined according to the treatment assignment at the time of randomization regardless of the actual study drug the participant might take during his/her participation in the study.

Arm/Group Title	Ruxolitininb 15mg + Standard of Care (SoC)	Ruxolitinib 5mg + Standard of Care (SoC)	Placebo + Standard of Care (SoC)
Arm/Group Description	Ruxolitinib 15mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Ruxolitinib 5mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Matching Placebo was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Measure Participants	77	85	47
Mean (Standard Deviation) [Days]	2.66 (6.073)	2.98 (6.745)	1.53 (4.690)

5. Secondary Outcome

Title	Vasopressor Free Days
Description	Number of days without use of vasopressor therapy
Time Frame	Study start to Day 29

Outcome Measure Data

Analysis Population Description

ITT population is defined according to the treatment assignment at the time of randomization regardless of the actual study drug the participant might take during his/her participation in the study.

Arm/Group Title	Ruxolitininb 15mg + Standard of Care (SoC)	Ruxolitinib 5mg + Standard of Care (SoC)	Placebo + Standard of Care (SoC)
Arm/Group Description	Ruxolitinib 15mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Ruxolitinib 5mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Matching Placebo was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Measure Participants	77	85	47
Mean (Standard Deviation) [Days]	8.95 (11.738)	7.53 (10.861)	4.47 (9.322)

6. Secondary Outcome

Title	Hospital Free Days
Description	Number of days Partcipant is out of the hospital
Time Frame	Study start to Day 29

Outcome Measure Data

Analysis Population Description

ITT population is defined according to the treatment assignment at the time of randomization regardless of the actual study drug the participant might take during his/her participation in the study.

Arm/Group Title	Ruxolitininb 15mg + Standard of Care (SoC)	Ruxolitinib 5mg + Standard of Care (SoC)	Placebo + Standard of Care (SoC)
Arm/Group Description	Ruxolitinib 15mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Ruxolitinib 5mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Matching Placebo was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Measure Participants	77	85	47
Mean (Standard Deviation) [Days]	2.09 (4.889)	2.35 (5.259)	1.38 (3.976)

7. Secondary Outcome

Title	Percentage of Participants With at Least 2-point Improvement in the COVID-19 Ordinal Scale
Description	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
Time Frame	Study start to Days 15 and 29

Outcome Measure Data

Analysis Population Description

ITT population is defined according to the treatment assignment at the time of randomization regardless of the actual study drug the participant might take during his/her participation in the study.

Arm/Group Title	Ruxolitininb 15mg + Standard of Care (SoC)	Ruxolitinib 5mg + Standard of Care (SoC)	Placebo + Standard of Care (SoC)
Arm/Group Description	Ruxolitinib 15mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Ruxolitinib 5mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Matching Placebo was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Measure Participants	77	87	47
Day 15	22.1 28.7%	15.3 17.6%	10.6 22.6%
Day 29	29.7 38.6%	25.3 29.1%	17.0 36.2%

8. Secondary Outcome

Title	Percentage of Participants With at Least 1-point Improvement in the COVID-19 Ordinal Scale
Description	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 Frame	Study start to Days 15 and 29

Outcome Measure Data

Analysis Population Description

ITT population is defined according to the treatment assignment at the time of randomization regardless of the actual study drug the participant might take during his/her participation in the study.

Arm/Group Title	Ruxolitininb 15mg + Standard of Care (SoC)	Ruxolitinib 5mg + Standard of Care (SoC)	Placebo + Standard of Care (SoC)
Arm/Group Description	Ruxolitinib 15mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Ruxolitinib 5mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Matching Placebo was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Measure Participants	77	87	47
Day 15	41.6 54%	32.9 37.8%	21.3 45.3%
Day 29	43.2 56.1%	32.5 37.4%	17.0 36.2%

9. Secondary Outcome

Title	Time to Improvement From Baseline Category to Earliest 1-point Improvement in the COVID-19 Ordinal Scale
Description	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
Time Frame	Study Start to Day 29

Outcome Measure Data

Analysis Population Description

ITT population is defined according to the treatment assignment at the time of randomization regardless of the actual study drug the participant might take during his/her participation in the study.

Arm/Group Title	Ruxolitininb 15mg + Standard of Care (SoC)	Ruxolitinib 5mg + Standard of Care (SoC)	Placebo + Standard of Care (SoC)
Arm/Group Description	Ruxolitinib 15mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Ruxolitinib 5mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Matching Placebo was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Measure Participants	50	49	20
Median (95% Confidence Interval) [Days]	0.91	0.75	0.61

10. Secondary Outcome

Title	Percentage of Participants With the COVID-19 Ordinal Scale Reported
Description	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
Time Frame	Study start to Day 29

Outcome Measure Data

Analysis Population Description

ITT population is defined according to the treatment assignment at the time of randomization regardless of the actual study drug the participant might take during his/her participation in the study. Please note that in the 15mg BID arm, 3 participants were missing scale reporting on Day 29. In the 5mg BID, 2 participants were lost to follow-up, and 2 were missing scale reporting.

Arm/Group Title	Ruxolitininb 15mg + Standard of Care (SoC)	Ruxolitinib 5mg + Standard of Care (SoC)	Placebo + Standard of Care (SoC)
Arm/Group Description	Ruxolitinib 15mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Ruxolitinib 5mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Matching Placebo was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Measure Participants	74	83	47
Score 0 = Uninfected	0	4.6	0
Score 1 = Ambulatory (no limitation of activities)	2.6	0	2.1
Score 2 = Ambulatory (limitation of activities)	16.9	16.1	10.6
Score 3 = Hospitalized/Mild Disease (no oxygen therapy)	0	1.1	0
Score 4 = Hospitalized/Mild Disease (oxygen therapy via mask or nasal prongs)	9.1	1.1	4.3
Score 5 = Hospitalized/Severe Disease (non-invasive ventilation or high-flow oxygen)	3.9	4.6	0.0
Score 6 = Hospitalized/Severe Disease (intubationand mechanical ventilization)	10.4	8.0	2.1
Score 7 = Hospitalized/Severe Disease (ventilation + additional organ support)	2.6	8.0	10.6
Score 8 - Death	50.6	51.7	70.2

11. Secondary Outcome

Title	Change in the COVID-19 9-point Ordinal Scale
Description	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
Time Frame	Study start to Days 15 and 29

Outcome Measure Data

Analysis Population Description

ITT population is defined according to the treatment assignment at the time of randomization regardless of the actual study drug the participant might take during his/her participation in the study. In the 15mg BID arm, 3 participants were missing scale reportingon Day 29. IN the 5mg BID, 2 participants were lost to follow-up, and 2 were missing scale reporting.

Arm/Group Title	Ruxolitininb 15mg + Standard of Care (SoC)	Ruxolitinib 5mg + Standard of Care (SoC)	Placebo + Standard of Care (SoC)
Arm/Group Description	Ruxolitinib 15mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Ruxolitinib 5mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Matching Placebo was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Measure Participants	77	87	47
Change from Day 1 to Day 15	-0.4 (1.80)	-0.2 (1.73)	0.6 (1.69)
Change from Day 1 to Day 29	-0.5 (2.53)	-0.4 (2.57)	0.4 (2.23)

12. Secondary Outcome

Title	Change in SOFA Score
Description	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).
Time Frame	from baseline to Days 3, 5, 8, 11, 15, and 29

Outcome Measure Data

Analysis Population Description

ITT population is defined according to the treatment assignment at the time of randomization regardless of the actual study drug the participant might take during his/her participation in the study. Numbers of participants decreased after Day 1 because data was no longer collected if a patient was discharged from ICU and/or deceased.

Arm/Group Title	Ruxolitininb 15mg + Standard of Care (SoC)	Ruxolitinib 5mg + Standard of Care (SoC)	Placebo + Standard of Care (SoC)
Arm/Group Description	Ruxolitinib 15mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Ruxolitinib 5mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Matching Placebo was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Measure Participants	77	87	47
Baseline - Day 1	9.2 (2.35)	9.6 (2.53)	9.4 (2.69)
Day 3	-0.1 (2.77)	0.4 (3.14)	2.6 (5.89)
Day 5	0.2 (4.27)	0.7 (4.58)	3.3 (6.60)
Day 8	1.9 (6.77)	2.0 (6.30)	4.5 (7.87)
Day 11	2.5 (7.64)	2.0 (7.02)	6.5 (8.26)
Day 15	4.2 (9.24)	4.1 (7.72)	10.3 (7.89)
Day 29	10.3 (8.54)	10.4 (7.04)	12.8 (5.41)

13. Secondary Outcome

Title	Number and Percentage of Participants With Treatment-related Side Effects and Serious Adverse Events
Description	Treatment-emergent AEs are judged as related by the investigator or have a missing causality.
Time Frame	Study start to Day 29

Outcome Measure Data

Analysis Population Description

The safety population includes all participants who received at least 1 dose of ruxolitinib/placebo.

Arm/Group Title	Ruxolitininb 15mg + Standard of Care (SoC)	Ruxolitinib 5mg + Standard of Care (SoC)	Placebo + Standard of Care (SoC)
Arm/Group Description	Ruxolitinib 15mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Ruxolitinib 5mg was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.	Matching Placebo was administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Measure Participants	77	87	45
Treatment-Emergent Adverse Events (TEAEs)	22 28.6%	23 26.4%	11 23.4%
Serious TEAEs	23 29.9%	21 24.1%	11 23.4%

Adverse Events

Time Frame	Up to approximately 2 months.
Adverse Event Reporting Description	All-Cause Mortality was monitored in all randomized participants and Serious and Other Adverse Events were assessed only in participants who received the intervention (i.e. the safety population).
Arm/Group Title	Ruxolitinib 15 mg BID		Ruxolitinib 5 mg BID		Placebo		Total
Arm/Group Description	Ruxolitinib 15 mg BID		Ruxolitinib 5 mg BID		Placebo		Total
All Cause Mortality
	Ruxolitinib 15 mg BID		Ruxolitinib 5 mg BID		Placebo		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/77 (54.5%)		48/87 (55.2%)		36/47 (76.6%)		124/209 (59.3%)
Serious Adverse Events
	Ruxolitinib 15 mg BID		Ruxolitinib 5 mg BID		Placebo		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/77 (29.9%)		21/87 (24.1%)		11/45 (24.4%)		55/209 (26.3%)
Blood and lymphatic system disorders
Anaemia	1/77 (1.3%)	1	0/87 (0%)	0	1/45 (2.2%)	1	2/209 (1%)	2
Thrombocytopenia	1/77 (1.3%)	1	0/87 (0%)	0	0/45 (0%)	0	1/209 (0.5%)	1
Cardiac disorders
Atrioventricular block complete	1/77 (1.3%)	1	0/87 (0%)	0	0/45 (0%)	0	1/209 (0.5%)	1
Bradycardia	0/77 (0%)	0	0/87 (0%)	0	1/45 (2.2%)	1	1/209 (0.5%)	1
Cardio-respiratory arrest	0/77 (0%)	0	0/87 (0%)	0	1/45 (2.2%)	1	1/209 (0.5%)	1
Cardiopulmonary failure	1/77 (1.3%)	1	1/87 (1.1%)	1	1/45 (2.2%)	1	3/209 (1.4%)	3
Myocardial infarction	0/77 (0%)	0	1/87 (1.1%)	1	0/45 (0%)	0	1/209 (0.5%)	1
Pulseless electrical activity	1/77 (1.3%)	1	0/87 (0%)	0	1/45 (2.2%)	1	2/209 (1%)	2
Torsade de pointes	0/77 (0%)	0	1/87 (1.1%)	1	0/45 (0%)	0	1/209 (0.5%)	1
Gastrointestinal disorders
Duodenal ulcer perforation	1/77 (1.3%)	1	0/87 (0%)	0	0/45 (0%)	0	1/209 (0.5%)	1
Ileus	0/77 (0%)	0	0/87 (0%)	0	1/45 (2.2%)	1	1/209 (0.5%)	1
Intestinal perforation	0/77 (0%)	0	0/87 (0%)	0	1/45 (2.2%)	1	1/209 (0.5%)	1
Lower gastrointestinal haemorrhage	0/77 (0%)	0	2/87 (2.3%)	2	0/45 (0%)	0	2/209 (1%)	2
Rectal haemorrhage	0/77 (0%)	0	1/87 (1.1%)	1	1/45 (2.2%)	1	2/209 (1%)	2
Hepatobiliary disorders
Cholestasis	0/77 (0%)	0	1/87 (1.1%)	1	0/45 (0%)	0	1/209 (0.5%)	1
Infections and infestations
Aspergillus infection	0/77 (0%)	0	1/87 (1.1%)	1	0/45 (0%)	0	1/209 (0.5%)	1
Fungaemia	1/77 (1.3%)	1	0/87 (0%)	0	0/45 (0%)	0	1/209 (0.5%)	1
Hepatic infection	0/77 (0%)	0	1/87 (1.1%)	1	0/45 (0%)	0	1/209 (0.5%)	1
Pneumonia	2/77 (2.6%)	3	4/87 (4.6%)	4	2/45 (4.4%)	2	8/209 (3.8%)	9
Pneumonia bacterial	0/77 (0%)	0	0/87 (0%)	0	1/45 (2.2%)	1	1/209 (0.5%)	1
Pneumonia pseudomonal	0/77 (0%)	0	0/87 (0%)	0	1/45 (2.2%)	1	1/209 (0.5%)	1
Pneumonia staphylococcal	1/77 (1.3%)	1	1/87 (1.1%)	1	0/45 (0%)	0	2/209 (1%)	2
Sepsis	3/77 (3.9%)	3	1/87 (1.1%)	1	0/45 (0%)	0	4/209 (1.9%)	4
Staphylococcal bacteraemia	0/77 (0%)	0	1/87 (1.1%)	1	0/45 (0%)	0	1/209 (0.5%)	1
Staphylococcal sepsis	1/77 (1.3%)	1	0/87 (0%)	0	0/45 (0%)	0	1/209 (0.5%)	1
Streptococcal bacteraemia	0/77 (0%)	0	0/87 (0%)	0	1/45 (2.2%)	1	1/209 (0.5%)	1
Strongyloidiasis	1/77 (1.3%)	1	0/87 (0%)	0	0/45 (0%)	0	1/209 (0.5%)	1
Urinary tract infection bacterial	0/77 (0%)	0	0/87 (0%)	0	1/45 (2.2%)	1	1/209 (0.5%)	1
Vascular device infection	1/77 (1.3%)	1	1/87 (1.1%)	1	0/45 (0%)	0	2/209 (1%)	2
Injury, poisoning and procedural complications
Endotracheal intubation complication	0/77 (0%)	0	1/87 (1.1%)	1	0/45 (0%)	0	1/209 (0.5%)	1
Investigations
Alanine aminotransferase increased	3/77 (3.9%)	3	1/87 (1.1%)	1	1/45 (2.2%)	1	5/209 (2.4%)	5
Aspartate aminotransferase increased	2/77 (2.6%)	2	1/87 (1.1%)	1	1/45 (2.2%)	1	4/209 (1.9%)	4
Blood alkaline phosphatase increased	0/77 (0%)	0	2/87 (2.3%)	2	0/45 (0%)	0	2/209 (1%)	2
Blood creatinine increased	1/77 (1.3%)	1	0/87 (0%)	0	0/45 (0%)	0	1/209 (0.5%)	1
Oxygen saturation decreased	1/77 (1.3%)	1	0/87 (0%)	0	0/45 (0%)	0	1/209 (0.5%)	1
Metabolism and nutrition disorders
Acidosis	1/77 (1.3%)	1	0/87 (0%)	0	0/45 (0%)	0	1/209 (0.5%)	1
Hyperkalaemia	0/77 (0%)	0	0/87 (0%)	0	1/45 (2.2%)	1	1/209 (0.5%)	1
Hyperphosphataemia	1/77 (1.3%)	1	0/87 (0%)	0	0/45 (0%)	0	1/209 (0.5%)	1
Nervous system disorders
Cerebral haemorrhage	0/77 (0%)	0	2/87 (2.3%)	2	0/45 (0%)	0	2/209 (1%)	2
Product Issues
Device dislocation	0/77 (0%)	0	1/87 (1.1%)	1	0/45 (0%)	0	1/209 (0.5%)	1
Renal and urinary disorders
Acute kidney injury	1/77 (1.3%)	1	2/87 (2.3%)	2	0/45 (0%)	0	3/209 (1.4%)	3
Haematuria	1/77 (1.3%)	1	0/87 (0%)	0	0/45 (0%)	0	1/209 (0.5%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/77 (1.3%)	1	0/87 (0%)	0	0/45 (0%)	0	1/209 (0.5%)	1
Aspiration	1/77 (1.3%)	1	0/87 (0%)	0	0/45 (0%)	0	1/209 (0.5%)	1
Hypoxia	1/77 (1.3%)	1	1/87 (1.1%)	1	3/45 (6.7%)	3	5/209 (2.4%)	5
Pneumothorax	3/77 (3.9%)	3	0/87 (0%)	0	1/45 (2.2%)	1	4/209 (1.9%)	4
Pulmonary oedema	1/77 (1.3%)	1	0/87 (0%)	0	0/45 (0%)	0	1/209 (0.5%)	1
Vascular disorders
Deep vein thrombosis	1/77 (1.3%)	1	0/87 (0%)	0	0/45 (0%)	0	1/209 (0.5%)	1
Haematoma	0/77 (0%)	0	1/87 (1.1%)	1	0/45 (0%)	0	1/209 (0.5%)	1
Hypertension	2/77 (2.6%)	2	1/87 (1.1%)	1	0/45 (0%)	0	3/209 (1.4%)	3
Hypotension	1/77 (1.3%)	1	3/87 (3.4%)	4	1/45 (2.2%)	1	5/209 (2.4%)	6
Peripheral arterial occlusive disease	0/77 (0%)	0	1/87 (1.1%)	1	0/45 (0%)	0	1/209 (0.5%)	1
Peripheral ischaemia	0/77 (0%)	0	2/87 (2.3%)	2	0/45 (0%)	0	2/209 (1%)	2
Shock	1/77 (1.3%)	1	0/87 (0%)	0	0/45 (0%)	0	1/209 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Ruxolitinib 15 mg BID		Ruxolitinib 5 mg BID		Placebo		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/77 (45.5%)		46/87 (52.9%)		21/45 (46.7%)		102/209 (48.8%)
Blood and lymphatic system disorders
Anaemia	12/77 (15.6%)	13	21/87 (24.1%)	23	9/45 (20%)	9	42/209 (20.1%)	45
Cardiac disorders
Atrial fibrillation	1/77 (1.3%)	1	5/87 (5.7%)	6	3/45 (6.7%)	3	9/209 (4.3%)	10
Gastrointestinal disorders
Constipation	5/77 (6.5%)	5	4/87 (4.6%)	4	2/45 (4.4%)	2	11/209 (5.3%)	11
Vomiting	5/77 (6.5%)	10	4/87 (4.6%)	5	1/45 (2.2%)	1	10/209 (4.8%)	16
General disorders
Oedema peripheral	2/77 (2.6%)	2	5/87 (5.7%)	6	0/45 (0%)	0	7/209 (3.3%)	8
Pyrexia	2/77 (2.6%)	2	5/87 (5.7%)	7	4/45 (8.9%)	4	11/209 (5.3%)	13
Infections and infestations
Bacteraemia	1/77 (1.3%)	1	5/87 (5.7%)	5	0/45 (0%)	0	6/209 (2.9%)	6
Pneumonia staphylococcal	5/77 (6.5%)	5	2/87 (2.3%)	2	1/45 (2.2%)	1	8/209 (3.8%)	8
Investigations
Alanine aminotransferase increased	9/77 (11.7%)	9	12/87 (13.8%)	13	5/45 (11.1%)	5	26/209 (12.4%)	27
Aspartate aminotransferase increased	10/77 (13%)	10	11/87 (12.6%)	12	3/45 (6.7%)	3	24/209 (11.5%)	25
Lymphocyte count decreased	3/77 (3.9%)	5	4/87 (4.6%)	7	3/45 (6.7%)	4	10/209 (4.8%)	16
Metabolism and nutrition disorders
Hyperglycaemia	3/77 (3.9%)	4	8/87 (9.2%)	9	1/45 (2.2%)	1	12/209 (5.7%)	14
Hyperkalaemia	4/77 (5.2%)	4	3/87 (3.4%)	3	3/45 (6.7%)	3	10/209 (4.8%)	10
Hypermagnesaemia	5/77 (6.5%)	7	4/87 (4.6%)	4	1/45 (2.2%)	1	10/209 (4.8%)	12
Hypernatraemia	8/77 (10.4%)	13	7/87 (8%)	8	7/45 (15.6%)	7	22/209 (10.5%)	28
Hypoalbuminaemia	1/77 (1.3%)	1	7/87 (8%)	7	4/45 (8.9%)	4	12/209 (5.7%)	12
Hypokalaemia	9/77 (11.7%)	11	9/87 (10.3%)	11	4/45 (8.9%)	4	22/209 (10.5%)	26
Hyponatraemia	3/77 (3.9%)	4	2/87 (2.3%)	2	3/45 (6.7%)	4	8/209 (3.8%)	10
Hypophosphataemia	5/77 (6.5%)	5	6/87 (6.9%)	8	2/45 (4.4%)	2	13/209 (6.2%)	15
Psychiatric disorders
Anxiety	6/77 (7.8%)	6	4/87 (4.6%)	4	1/45 (2.2%)	1	11/209 (5.3%)	11
Skin and subcutaneous tissue disorders
Decubitus ulcer	3/77 (3.9%)	4	4/87 (4.6%)	5	3/45 (6.7%)	4	10/209 (4.8%)	13
Skin ulcer	3/77 (3.9%)	4	5/87 (5.7%)	6	3/45 (6.7%)	3	11/209 (5.3%)	13
Vascular disorders
Hypertension	5/77 (6.5%)	5	11/87 (12.6%)	12	5/45 (11.1%)	5	21/209 (10%)	22
Hypotension	4/77 (5.2%)	5	3/87 (3.4%)	3	2/45 (4.4%)	2	9/209 (4.3%)	10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Following the first publication, the Institution and/or Principal Investigator may publish data or results from the Study, provided, however, that the Institution and/or Principal Investigator submits the proposed publication to the Sponsor for review at least sixty (60) days prior to the date of the proposed publication. Sponsor may remove from the proposed publication any information that is considered confidential and/or proprietary other than Study data and results.