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

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: COVID-19
• Interventions: Drug: Placebo; Drug: Ruxolitinib
• Enrollment: 211

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 Details

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
Reason Not Completed
Death	42	48	36
Withdrawal by Subject	0	2	0

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 Number of Baseline Participants		77	87	47	211
Baseline Analysis Population Description		Intent-to-treat (ITT) population included all participants who were randomized to the study.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	77 participants	87 participants	47 participants	211 participants
		63.6 (12.92)	63.6 (12.25)	62.5 (13.34)	63.4 (12.69)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	77 participants	87 participants	47 participants	211 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); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	77 participants	87 participants	47 participants	211 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); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	77 participants	87 participants	47 participants	211 participants
	American Indian or Alaska Native	0 0.0%	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 0.0%	0 0.0%
	Black or African American	9 11.7%	12 13.8%	5 10.6%	26 12.3%
	White	57 74.0%	61 70.1%	31 66.0%	149 70.6%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	8 10.4%	11 12.6%	8 17.0%	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.
Overall Number of Participants Analyzed	77	85	47
Measure Type: Number; Unit of Measure: Percentage
	50.6	52.9	70.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ruxolitininb 15mg + Standard of Care (SoC)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0292
	Comments	[Not Specified]
	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
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib 5mg + Standard of Care (SoC)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0280
	Comments	[Not Specified]
	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
	Estimation Comments	[Not Specified]

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.
Overall Number of Participants Analyzed	77	85	47
Mean (Standard Deviation); Unit of Measure: 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.
Overall Number of Participants Analyzed	77	85	47
Mean (Standard Deviation); Unit of Measure: 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.
Overall Number of Participants Analyzed	77	85	47
Mean (Standard Deviation); Unit of Measure: 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.
Overall Number of Participants Analyzed	77	85	47
Mean (Standard Deviation); Unit of Measure: 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.
Overall Number of Participants Analyzed	77	85	47
Mean (Standard Deviation); Unit of Measure: 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.
Overall Number of Participants Analyzed		77	87	47
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
Day 15	Number Analyzed	77 participants	85 participants	47 participants
		22.1; (13.4 to 33.)	15.3; (8.4 to 24.7)	10.6; (3.5 to 23.1)
Day 29	Number Analyzed	74 participants	83 participants	47 participants
		29.7; (19.7 to 41.5)	25.3; (16.4 to 36.0)	17.0; (7.6 to 30.8)

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.
Overall Number of Participants Analyzed		77	87	47
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
Day 15	Number Analyzed	77 participants	85 participants	47 participants
		41.6; (30.4 to 53.4)	32.9; (23.1 to 44.0)	21.3; (10.7 to 35.7)
Day 29	Number Analyzed	77 participants	87 participants	47 participants
		43.2; (31.8 to 55.3)	32.5; (22.6 to 43.7)	17.0; (7.6 to 30.8)

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.
Overall Number of Participants Analyzed	50	49	20
Median (95% Confidence Interval); Unit of Measure: Days
	0.91; (0.711 to 0.992)	0.75; (0.614 to 0.867)	0.61; (0.408 to 0.818)

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.
Overall Number of Participants Analyzed	74	83	47
Measure Type: Number; Unit of Measure: Percentage
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.
Overall Number of Participants Analyzed		77	87	47
Mean (Standard Deviation); Unit of Measure: Score on a Scale
Change from Day 1 to Day 15	Number Analyzed	77 participants	85 participants	47 participants
		-0.4 (1.80)	-0.2 (1.73)	0.6 (1.69)
Change from Day 1 to Day 29	Number Analyzed	74 participants	83 participants	47 participants
		-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.
Overall Number of Participants Analyzed		77	87	47
Mean (Standard Deviation); Unit of Measure: Scores on a Scale
Baseline - Day 1	Number Analyzed	74 participants	87 participants	46 participants
		9.2 (2.35)	9.6 (2.53)	9.4 (2.69)
Day 3	Number Analyzed	76 participants	87 participants	46 participants
		-0.1 (2.77)	0.4 (3.14)	2.6 (5.89)
Day 5	Number Analyzed	76 participants	85 participants	47 participants
		0.2 (4.27)	0.7 (4.58)	3.3 (6.60)
Day 8	Number Analyzed	69 participants	83 participants	45 participants
		1.9 (6.77)	2.0 (6.30)	4.5 (7.87)
Day 11	Number Analyzed	69 participants	79 participants	42 participants
		2.5 (7.64)	2.0 (7.02)	6.5 (8.26)
Day 15	Number Analyzed	67 participants	74 participants	40 participants
		4.2 (9.24)	4.1 (7.72)	10.3 (7.89)
Day 29	Number Analyzed	52 participants	60 participants	38 participants
		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.
Overall Number of Participants Analyzed	77	87	45
Measure Type: Count of Participants; Unit of Measure: Participants
Treatment-Emergent Adverse Events (TEAEs)	22 28.6%	23 26.4%	11 24.4%
Serious TEAEs	23 29.9%	21 24.1%	11 24.4%

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 (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	42/77 (54.55%)		48/87 (55.17%)		36/47 (76.60%)		124/209 (59.33%)
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 (29.87%)		21/87 (24.14%)		11/45 (24.44%)		55/209 (26.32%)
Blood and lymphatic system disorders
Anaemia † 1	1/77 (1.30%)	1	0/87 (0.00%)	0	1/45 (2.22%)	1	2/209 (0.96%)	2
Thrombocytopenia † 1	1/77 (1.30%)	1	0/87 (0.00%)	0	0/45 (0.00%)	0	1/209 (0.48%)	1
Cardiac disorders
Atrioventricular block complete † 1	1/77 (1.30%)	1	0/87 (0.00%)	0	0/45 (0.00%)	0	1/209 (0.48%)	1
Bradycardia † 1	0/77 (0.00%)	0	0/87 (0.00%)	0	1/45 (2.22%)	1	1/209 (0.48%)	1
Cardio-respiratory arrest † 1	0/77 (0.00%)	0	0/87 (0.00%)	0	1/45 (2.22%)	1	1/209 (0.48%)	1
Cardiopulmonary failure † 1	1/77 (1.30%)	1	1/87 (1.15%)	1	1/45 (2.22%)	1	3/209 (1.44%)	3
Myocardial infarction † 1	0/77 (0.00%)	0	1/87 (1.15%)	1	0/45 (0.00%)	0	1/209 (0.48%)	1
Pulseless electrical activity † 1	1/77 (1.30%)	1	0/87 (0.00%)	0	1/45 (2.22%)	1	2/209 (0.96%)	2
Torsade de pointes † 1	0/77 (0.00%)	0	1/87 (1.15%)	1	0/45 (0.00%)	0	1/209 (0.48%)	1
Gastrointestinal disorders
Duodenal ulcer perforation † 1	1/77 (1.30%)	1	0/87 (0.00%)	0	0/45 (0.00%)	0	1/209 (0.48%)	1
Ileus † 1	0/77 (0.00%)	0	0/87 (0.00%)	0	1/45 (2.22%)	1	1/209 (0.48%)	1
Intestinal perforation † 1	0/77 (0.00%)	0	0/87 (0.00%)	0	1/45 (2.22%)	1	1/209 (0.48%)	1
Lower gastrointestinal haemorrhage † 1	0/77 (0.00%)	0	2/87 (2.30%)	2	0/45 (0.00%)	0	2/209 (0.96%)	2
Rectal haemorrhage † 1	0/77 (0.00%)	0	1/87 (1.15%)	1	1/45 (2.22%)	1	2/209 (0.96%)	2
Hepatobiliary disorders
Cholestasis † 1	0/77 (0.00%)	0	1/87 (1.15%)	1	0/45 (0.00%)	0	1/209 (0.48%)	1
Infections and infestations
Aspergillus infection † 1	0/77 (0.00%)	0	1/87 (1.15%)	1	0/45 (0.00%)	0	1/209 (0.48%)	1
Fungaemia † 1	1/77 (1.30%)	1	0/87 (0.00%)	0	0/45 (0.00%)	0	1/209 (0.48%)	1
Hepatic infection † 1	0/77 (0.00%)	0	1/87 (1.15%)	1	0/45 (0.00%)	0	1/209 (0.48%)	1
Pneumonia † 1	2/77 (2.60%)	3	4/87 (4.60%)	4	2/45 (4.44%)	2	8/209 (3.83%)	9
Pneumonia bacterial † 1	0/77 (0.00%)	0	0/87 (0.00%)	0	1/45 (2.22%)	1	1/209 (0.48%)	1
Pneumonia pseudomonal † 1	0/77 (0.00%)	0	0/87 (0.00%)	0	1/45 (2.22%)	1	1/209 (0.48%)	1
Pneumonia staphylococcal † 1	1/77 (1.30%)	1	1/87 (1.15%)	1	0/45 (0.00%)	0	2/209 (0.96%)	2
Sepsis † 1	3/77 (3.90%)	3	1/87 (1.15%)	1	0/45 (0.00%)	0	4/209 (1.91%)	4
Staphylococcal bacteraemia † 1	0/77 (0.00%)	0	1/87 (1.15%)	1	0/45 (0.00%)	0	1/209 (0.48%)	1
Staphylococcal sepsis † 1	1/77 (1.30%)	1	0/87 (0.00%)	0	0/45 (0.00%)	0	1/209 (0.48%)	1
Streptococcal bacteraemia † 1	0/77 (0.00%)	0	0/87 (0.00%)	0	1/45 (2.22%)	1	1/209 (0.48%)	1
Strongyloidiasis † 1	1/77 (1.30%)	1	0/87 (0.00%)	0	0/45 (0.00%)	0	1/209 (0.48%)	1
Urinary tract infection bacterial † 1	0/77 (0.00%)	0	0/87 (0.00%)	0	1/45 (2.22%)	1	1/209 (0.48%)	1
Vascular device infection † 1	1/77 (1.30%)	1	1/87 (1.15%)	1	0/45 (0.00%)	0	2/209 (0.96%)	2
Injury, poisoning and procedural complications
Endotracheal intubation complication † 1	0/77 (0.00%)	0	1/87 (1.15%)	1	0/45 (0.00%)	0	1/209 (0.48%)	1
Investigations
Alanine aminotransferase increased † 1	3/77 (3.90%)	3	1/87 (1.15%)	1	1/45 (2.22%)	1	5/209 (2.39%)	5
Aspartate aminotransferase increased † 1	2/77 (2.60%)	2	1/87 (1.15%)	1	1/45 (2.22%)	1	4/209 (1.91%)	4
Blood alkaline phosphatase increased † 1	0/77 (0.00%)	0	2/87 (2.30%)	2	0/45 (0.00%)	0	2/209 (0.96%)	2
Blood creatinine increased † 1	1/77 (1.30%)	1	0/87 (0.00%)	0	0/45 (0.00%)	0	1/209 (0.48%)	1
Oxygen saturation decreased † 1	1/77 (1.30%)	1	0/87 (0.00%)	0	0/45 (0.00%)	0	1/209 (0.48%)	1
Metabolism and nutrition disorders
Acidosis † 1	1/77 (1.30%)	1	0/87 (0.00%)	0	0/45 (0.00%)	0	1/209 (0.48%)	1
Hyperkalaemia † 1	0/77 (0.00%)	0	0/87 (0.00%)	0	1/45 (2.22%)	1	1/209 (0.48%)	1
Hyperphosphataemia † 1	1/77 (1.30%)	1	0/87 (0.00%)	0	0/45 (0.00%)	0	1/209 (0.48%)	1
Nervous system disorders
Cerebral haemorrhage † 1	0/77 (0.00%)	0	2/87 (2.30%)	2	0/45 (0.00%)	0	2/209 (0.96%)	2
Product Issues
Device dislocation † 1	0/77 (0.00%)	0	1/87 (1.15%)	1	0/45 (0.00%)	0	1/209 (0.48%)	1
Renal and urinary disorders
Acute kidney injury † 1	1/77 (1.30%)	1	2/87 (2.30%)	2	0/45 (0.00%)	0	3/209 (1.44%)	3
Haematuria † 1	1/77 (1.30%)	1	0/87 (0.00%)	0	0/45 (0.00%)	0	1/209 (0.48%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome † 1	1/77 (1.30%)	1	0/87 (0.00%)	0	0/45 (0.00%)	0	1/209 (0.48%)	1
Aspiration † 1	1/77 (1.30%)	1	0/87 (0.00%)	0	0/45 (0.00%)	0	1/209 (0.48%)	1
Hypoxia † 1	1/77 (1.30%)	1	1/87 (1.15%)	1	3/45 (6.67%)	3	5/209 (2.39%)	5
Pneumothorax † 1	3/77 (3.90%)	3	0/87 (0.00%)	0	1/45 (2.22%)	1	4/209 (1.91%)	4
Pulmonary oedema † 1	1/77 (1.30%)	1	0/87 (0.00%)	0	0/45 (0.00%)	0	1/209 (0.48%)	1
Vascular disorders
Deep vein thrombosis † 1	1/77 (1.30%)	1	0/87 (0.00%)	0	0/45 (0.00%)	0	1/209 (0.48%)	1
Haematoma † 1	0/77 (0.00%)	0	1/87 (1.15%)	1	0/45 (0.00%)	0	1/209 (0.48%)	1
Hypertension † 1	2/77 (2.60%)	2	1/87 (1.15%)	1	0/45 (0.00%)	0	3/209 (1.44%)	3
Hypotension † 1	1/77 (1.30%)	1	3/87 (3.45%)	4	1/45 (2.22%)	1	5/209 (2.39%)	6
Peripheral arterial occlusive disease † 1	0/77 (0.00%)	0	1/87 (1.15%)	1	0/45 (0.00%)	0	1/209 (0.48%)	1
Peripheral ischaemia † 1	0/77 (0.00%)	0	2/87 (2.30%)	2	0/45 (0.00%)	0	2/209 (0.96%)	2
Shock † 1	1/77 (1.30%)	1	0/87 (0.00%)	0	0/45 (0.00%)	0	1/209 (0.48%)	1
1 Term from vocabulary, MedDRA 22; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	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 (45.45%)		46/87 (52.87%)		21/45 (46.67%)		102/209 (48.80%)
Blood and lymphatic system disorders
Anaemia † 1	12/77 (15.58%)	13	21/87 (24.14%)	23	9/45 (20.00%)	9	42/209 (20.10%)	45
Cardiac disorders
Atrial fibrillation † 1	1/77 (1.30%)	1	5/87 (5.75%)	6	3/45 (6.67%)	3	9/209 (4.31%)	10
Gastrointestinal disorders
Constipation † 1	5/77 (6.49%)	5	4/87 (4.60%)	4	2/45 (4.44%)	2	11/209 (5.26%)	11
Vomiting † 1	5/77 (6.49%)	10	4/87 (4.60%)	5	1/45 (2.22%)	1	10/209 (4.78%)	16
General disorders
Oedema peripheral † 1	2/77 (2.60%)	2	5/87 (5.75%)	6	0/45 (0.00%)	0	7/209 (3.35%)	8
Pyrexia † 1	2/77 (2.60%)	2	5/87 (5.75%)	7	4/45 (8.89%)	4	11/209 (5.26%)	13
Infections and infestations
Bacteraemia † 1	1/77 (1.30%)	1	5/87 (5.75%)	5	0/45 (0.00%)	0	6/209 (2.87%)	6
Pneumonia staphylococcal † 1	5/77 (6.49%)	5	2/87 (2.30%)	2	1/45 (2.22%)	1	8/209 (3.83%)	8
Investigations
Alanine aminotransferase increased † 1	9/77 (11.69%)	9	12/87 (13.79%)	13	5/45 (11.11%)	5	26/209 (12.44%)	27
Aspartate aminotransferase increased † 1	10/77 (12.99%)	10	11/87 (12.64%)	12	3/45 (6.67%)	3	24/209 (11.48%)	25
Lymphocyte count decreased † 1	3/77 (3.90%)	5	4/87 (4.60%)	7	3/45 (6.67%)	4	10/209 (4.78%)	16
Metabolism and nutrition disorders
Hyperglycaemia † 1	3/77 (3.90%)	4	8/87 (9.20%)	9	1/45 (2.22%)	1	12/209 (5.74%)	14
Hyperkalaemia † 1	4/77 (5.19%)	4	3/87 (3.45%)	3	3/45 (6.67%)	3	10/209 (4.78%)	10
Hypermagnesaemia † 1	5/77 (6.49%)	7	4/87 (4.60%)	4	1/45 (2.22%)	1	10/209 (4.78%)	12
Hypernatraemia † 1	8/77 (10.39%)	13	7/87 (8.05%)	8	7/45 (15.56%)	7	22/209 (10.53%)	28
Hypoalbuminaemia † 1	1/77 (1.30%)	1	7/87 (8.05%)	7	4/45 (8.89%)	4	12/209 (5.74%)	12
Hypokalaemia † 1	9/77 (11.69%)	11	9/87 (10.34%)	11	4/45 (8.89%)	4	22/209 (10.53%)	26
Hyponatraemia † 1	3/77 (3.90%)	4	2/87 (2.30%)	2	3/45 (6.67%)	4	8/209 (3.83%)	10
Hypophosphataemia † 1	5/77 (6.49%)	5	6/87 (6.90%)	8	2/45 (4.44%)	2	13/209 (6.22%)	15
Psychiatric disorders
Anxiety † 1	6/77 (7.79%)	6	4/87 (4.60%)	4	1/45 (2.22%)	1	11/209 (5.26%)	11
Skin and subcutaneous tissue disorders
Decubitus ulcer † 1	3/77 (3.90%)	4	4/87 (4.60%)	5	3/45 (6.67%)	4	10/209 (4.78%)	13
Skin ulcer † 1	3/77 (3.90%)	4	5/87 (5.75%)	6	3/45 (6.67%)	3	11/209 (5.26%)	13
Vascular disorders
Hypertension † 1	5/77 (6.49%)	5	11/87 (12.64%)	12	5/45 (11.11%)	5	21/209 (10.05%)	22
Hypotension † 1	4/77 (5.19%)	5	3/87 (3.45%)	3	2/45 (4.44%)	2	9/209 (4.31%)	10
1 Term from vocabulary, MedDRA 22; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Study Director
• Organization: Incyte Corporation
• Phone: 1-855-463-3463
• EMail: medinfo@incyte.com

• Responsible Party: Incyte Corporation
• ClinicalTrials.gov Identifier: NCT04377620
• Other Study ID Numbers: INCB 18424-369
• First Submitted: May 4, 2020
• First Posted: May 6, 2020
• Results First Submitted: November 17, 2021
• Results First Posted: January 19, 2022
• Last Update Posted: January 19, 2022