Assessment of Efficacy and Safety of Ruxolitinib in Participants With COVID-19-Associated ARDS Who Require Mechanical Ventilation (RUXCOVID-DEVENT)
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 |
---|---|---|
|
Phase 3 |
Study Design
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:
|
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:
|
Outcome Measures
Primary Outcome Measures
- 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
- Number of Ventilator Free Days [Study start to Day 29]
Number of days participant did not require mechanical ventilation
- Number of ICU Free Days [Study start to Day 29]
Number of days participant is out of the ICU
- Oxygen Free Days [Study start to Day 29]
Number of days participant did not receive supplemental oxygen
- Vasopressor Free Days [Study start to Day 29]
Number of days without use of vasopressor therapy
- Hospital Free Days [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 [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 [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 [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 [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 [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 [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 [Study start to Day 29]
Treatment-emergent AEs are judged as related by the investigator or have a missing causality.
Eligibility Criteria
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.
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)
More Information
Publications
None provided.- INCB 18424-369
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
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 |
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)
|
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)
|
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)
|
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)
|
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)
|
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%
|
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%
|
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
|
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
|
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)
|
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)
|
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
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.
Results Point of Contact
Name/Title | Study Director |
---|---|
Organization | Incyte Corporation |
Phone | 1-855-463-3463 |
medinfo@incyte.com |
- INCB 18424-369