Trial Outcomes & Findings for Controlled Myelofibrosis Study With Oral Janus-associated Kinase (JAK) Inhibitor Treatment-II: The COMFORT-II Trial (NCT NCT00934544)
NCT ID: NCT00934544
Last Updated: 2019-08-19
Results Overview
The change in spleen volume from baseline to week 48 was measured by magnetic resonance imaging (MRI) (or by computer tomography (CT) for participants unable to undergo MRI) and was calculated only for participants who had an evaluable spleen volume at baseline. The percentage of participants achieving a greater than or equal to 35% reduction in spleen volume from baseline to week 48 was then calculated by treatment group.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
219 participants
Primary outcome timeframe
Baseline, Week 48
Results posted on
2019-08-19
Participant Flow
Subjects were recruited from 9 countries located in Europe: Austria, Belgium, France, Germany, Italy, Netherlands, Spain, Sweden, and United Kingdom.
219 unique participants were randomized to either ruxolitinib or BAT. Of the 73 participants randomized to BAT, 45 were crossed over to ruxolitinib after a protocol-specified qualifying disease progression event.
Participant milestones
| Measure |
Ruxolitinib
5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
|
Best Available Therapy (BAT)
Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
|
Ruxolitinib After BAT (Cross-over)
5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
|
|---|---|---|---|
|
Primary Endpoint Analysis (Interim)
STARTED
|
146
|
73
|
0
|
|
Primary Endpoint Analysis (Interim)
COMPLETED
|
91
|
31
|
0
|
|
Primary Endpoint Analysis (Interim)
NOT COMPLETED
|
55
|
42
|
0
|
|
Overall Disposition at 5 Year Follow-up
STARTED
|
146
|
28
|
45
|
|
Overall Disposition at 5 Year Follow-up
Crossed Over After Qualifying Event
|
0
|
0
|
27
|
|
Overall Disposition at 5 Year Follow-up
Crossed Over After AMEND 5
|
0
|
0
|
12
|
|
Overall Disposition at 5 Year Follow-up
Crossed Over: Other
|
0
|
0
|
6
|
|
Overall Disposition at 5 Year Follow-up
COMPLETED
|
39
|
0
|
11
|
|
Overall Disposition at 5 Year Follow-up
NOT COMPLETED
|
107
|
28
|
34
|
Reasons for withdrawal
| Measure |
Ruxolitinib
5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
|
Best Available Therapy (BAT)
Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
|
Ruxolitinib After BAT (Cross-over)
5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
|
|---|---|---|---|
|
Primary Endpoint Analysis (Interim)
Adverse Event
|
12
|
4
|
0
|
|
Primary Endpoint Analysis (Interim)
Withdrawal by Subject
|
2
|
9
|
0
|
|
Primary Endpoint Analysis (Interim)
Protocol Violation
|
2
|
0
|
0
|
|
Primary Endpoint Analysis (Interim)
Disease Progression
|
1
|
3
|
0
|
|
Primary Endpoint Analysis (Interim)
Non-compliance with study Medication
|
2
|
0
|
0
|
|
Primary Endpoint Analysis (Interim)
Non-compliance with study procedures
|
0
|
1
|
0
|
|
Primary Endpoint Analysis (Interim)
Other reasons
|
7
|
7
|
0
|
|
Primary Endpoint Analysis (Interim)
Entered extension phase
|
29
|
18
|
0
|
|
Overall Disposition at 5 Year Follow-up
Including stem cell transplantation
|
16
|
9
|
6
|
|
Overall Disposition at 5 Year Follow-up
Adverse Event
|
35
|
5
|
10
|
|
Overall Disposition at 5 Year Follow-up
Withdrawal by Subject
|
10
|
9
|
0
|
|
Overall Disposition at 5 Year Follow-up
Protocol Violation
|
2
|
0
|
5
|
|
Overall Disposition at 5 Year Follow-up
Disease progression
|
32
|
4
|
7
|
|
Overall Disposition at 5 Year Follow-up
Noncompliance with study medication
|
4
|
0
|
1
|
|
Overall Disposition at 5 Year Follow-up
Noncompliance with study procedures
|
0
|
1
|
0
|
|
Overall Disposition at 5 Year Follow-up
Lack of Efficacy
|
8
|
0
|
5
|
Baseline Characteristics
Controlled Myelofibrosis Study With Oral Janus-associated Kinase (JAK) Inhibitor Treatment-II: The COMFORT-II Trial
Baseline characteristics by cohort
| Measure |
Ruxolitinib
n=146 Participants
5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
|
Best Available Therapy (BAT)
n=73 Participants
Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
|
Total
n=219 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65.1 years
STANDARD_DEVIATION 9.74 • n=99 Participants
|
65.2 years
STANDARD_DEVIATION 10.27 • n=107 Participants
|
65.2 years
STANDARD_DEVIATION 9.89 • n=206 Participants
|
|
Sex: Female, Male
Female
|
63 Participants
n=99 Participants
|
31 Participants
n=107 Participants
|
94 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
83 Participants
n=99 Participants
|
42 Participants
n=107 Participants
|
125 Participants
n=206 Participants
|
|
Disease Profile - Type of Myelofibrosis (MF)
Primary Myelofibrosis
|
77 Participants
n=99 Participants
|
39 Participants
n=107 Participants
|
116 Participants
n=206 Participants
|
|
Disease Profile - Type of Myelofibrosis (MF)
Post-polycythemia vera-myelofibrosis
|
48 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
68 Participants
n=206 Participants
|
|
Disease Profile - Type of Myelofibrosis (MF)
Post-essential thrombocythemia-myelofibrosis
|
21 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
35 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 48Population: Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. The table included participants with non-missing baseline MRI measurement of spleen volume only.
The change in spleen volume from baseline to week 48 was measured by magnetic resonance imaging (MRI) (or by computer tomography (CT) for participants unable to undergo MRI) and was calculated only for participants who had an evaluable spleen volume at baseline. The percentage of participants achieving a greater than or equal to 35% reduction in spleen volume from baseline to week 48 was then calculated by treatment group.
Outcome measures
| Measure |
Ruxolitinib
n=144 Participants
5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
|
Best Available Therapy (BAT)
n=72 Participants
Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
|
Ruxolitinib - Grade 2
|
Ruxolitinib - Grade 3
|
Ruxolitinib - Missing
|
Best Available Therapy (BAT) - Grade 0
|
Best Available Therapy (BAT) - Grade 1
|
Best Available Therapy (BAT) - Grade 2
|
Best Available Therapy (BAT) - Grade 3
|
Best Available Therapy - Missing
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 48
|
28.5 Percentage of Participants
|
0 Percentage of Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, up to Year 5Population: Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. Treatment groups were defined according to the treatment assignment at the time of randomization.
DoMSR is defined as the interval between the first spleen volume measurement that is \>=35% reduction from baseline and the first scan that is no longer = 35% reduction AND that is a \>25% increase over nadir. It was evaluated using the Kaplan-Meier estimate for each treatment arm. The analysis was performed only for subjects who achieved greater than 35% reduction in spleen volume.
Outcome measures
| Measure |
Ruxolitinib
n=78 Participants
5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
|
Best Available Therapy (BAT)
n=1 Participants
Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
|
Ruxolitinib - Grade 2
|
Ruxolitinib - Grade 3
|
Ruxolitinib - Missing
|
Best Available Therapy (BAT) - Grade 0
|
Best Available Therapy (BAT) - Grade 1
|
Best Available Therapy (BAT) - Grade 2
|
Best Available Therapy (BAT) - Grade 3
|
Best Available Therapy - Missing
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Duration of Maintenance of Spleen Volume Reduction (Median)
|
3.22 years
Interval 1.65 to
Upper limit is not estimable
|
NA years
There was only one BAT patient responder (≥ 35% reduction in spleen volume) but no consecutive readings to determine any value for duration of response - no Median or CI possible to calculate
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, up to Year 5Population: Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. Treatment groups were defined according to the treatment assignment at the time of randomization.
This is defined as the interval between randomization and date of the first MRI showing a 35% reduction from baseline in spleen volume. The analysis was performed for participants who achieved a 35% reduction in spleen volume.
Outcome measures
| Measure |
Ruxolitinib
n=78 Participants
5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
|
Best Available Therapy (BAT)
n=1 Participants
Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
|
Ruxolitinib - Grade 2
|
Ruxolitinib - Grade 3
|
Ruxolitinib - Missing
|
Best Available Therapy (BAT) - Grade 0
|
Best Available Therapy (BAT) - Grade 1
|
Best Available Therapy (BAT) - Grade 2
|
Best Available Therapy (BAT) - Grade 3
|
Best Available Therapy - Missing
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Duration of Maintenance of Spleen Volume Reduction (Kaplan-Meier Estimates)
1.0 year
|
0.72 probability of response
Interval 0.6 to 0.81
|
NA probability of response
There was only one BAT patient responder (≥ 35% reduction in spleen volume) but no consecutive readings to determine any value for duration of response - no Median or CI possible to calculate
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Duration of Maintenance of Spleen Volume Reduction (Kaplan-Meier Estimates)
1.5 years
|
0.67 probability of response
Interval 0.55 to 0.77
|
NA probability of response
There was only one BAT patient responder (≥ 35% reduction in spleen volume) but no consecutive readings to determine any value for duration of response - no Median or CI possible to calculate
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Duration of Maintenance of Spleen Volume Reduction (Kaplan-Meier Estimates)
5.0 years
|
0.48 probability of response
Interval 0.35 to 0.6
|
NA probability of response
There was only one BAT patient responder (≥ 35% reduction in spleen volume) but no consecutive readings to determine any value for duration of response - no Median or CI possible to calculate
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Duration of Maintenance of Spleen Volume Reduction (Kaplan-Meier Estimates)
2.0 years
|
0.63 probability of response
Interval 0.5 to 0.73
|
NA probability of response
There was only one BAT patient responder (≥ 35% reduction in spleen volume) but no consecutive readings to determine any value for duration of response - no Median or CI possible to calculate
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Duration of Maintenance of Spleen Volume Reduction (Kaplan-Meier Estimates)
2.5 years
|
0.54 probability of response
Interval 0.41 to 0.65
|
NA probability of response
There was only one BAT patient responder (≥ 35% reduction in spleen volume) but no consecutive readings to determine any value for duration of response - no Median or CI possible to calculate
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Duration of Maintenance of Spleen Volume Reduction (Kaplan-Meier Estimates)
3.0 years
|
0.51 probability of response
Interval 0.38 to 0.62
|
NA probability of response
There was only one BAT patient responder (≥ 35% reduction in spleen volume) but no consecutive readings to determine any value for duration of response - no Median or CI possible to calculate
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Duration of Maintenance of Spleen Volume Reduction (Kaplan-Meier Estimates)
3.5 years
|
0.48 probability of response
Interval 0.35 to 0.6
|
NA probability of response
There was only one BAT patient responder (≥ 35% reduction in spleen volume) but no consecutive readings to determine any value for duration of response - no Median or CI possible to calculate
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Duration of Maintenance of Spleen Volume Reduction (Kaplan-Meier Estimates)
4.0 years
|
0.48 probability of response
Interval 0.35 to 0.6
|
NA probability of response
There was only one BAT patient responder (≥ 35% reduction in spleen volume) but no consecutive readings to determine any value for duration of response - no Median or CI possible to calculate
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Duration of Maintenance of Spleen Volume Reduction (Kaplan-Meier Estimates)
4.5 years
|
0.48 probability of response
Interval 0.35 to 0.6
|
NA probability of response
There was only one BAT patient responder (≥ 35% reduction in spleen volume) but no consecutive readings to determine any value for duration of response - no Median or CI possible to calculate
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. The table included participants with non-missing baseline MRI measurement of spleen volume only.
The change in spleen volume from baseline to week 24 was measured by magnetic resonance imaging (MRI) (or by computer tomography (CT) for participants unable to undergo MRI) and was calculated only for participants who had an evaluable spleen volume at baseline. The percentage of participants achieving a greater than or equal to 35% reduction in spleen volume from baseline to week 24 was then calculated by treatment group.
Outcome measures
| Measure |
Ruxolitinib
n=144 Participants
5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
|
Best Available Therapy (BAT)
n=72 Participants
Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
|
Ruxolitinib - Grade 2
|
Ruxolitinib - Grade 3
|
Ruxolitinib - Missing
|
Best Available Therapy (BAT) - Grade 0
|
Best Available Therapy (BAT) - Grade 1
|
Best Available Therapy (BAT) - Grade 2
|
Best Available Therapy (BAT) - Grade 3
|
Best Available Therapy - Missing
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 24
|
31.9 Percentage of Participants
|
0 Percentage of Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Time from randomization and date of the first MRI showing at least 35% reduction from baseline in spleen volumePopulation: Full analysis set (FAS)
This is defined as the interval between randomization and date of the first MRI showing at least 35% reduction from baseline in spleen volume. The analysis was performed for participants who achieved a 35% reduction in spleen volume
Outcome measures
| Measure |
Ruxolitinib
n=69 Participants
5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
|
Best Available Therapy (BAT)
n=1 Participants
Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
|
Ruxolitinib - Grade 2
|
Ruxolitinib - Grade 3
|
Ruxolitinib - Missing
|
Best Available Therapy (BAT) - Grade 0
|
Best Available Therapy (BAT) - Grade 1
|
Best Available Therapy (BAT) - Grade 2
|
Best Available Therapy (BAT) - Grade 3
|
Best Available Therapy - Missing
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Time to First at Least 35% Reduction in Spleen Volume From Baseline by Treatment (Primary Analysis)
12 weeks
|
0.23 probability of response
Interval 0.14 to 0.34
|
0 probability of response
There was only one BAT patient responder (≥ 35% reduction in spleen volume) but no consecutive readings to determine any value for duration of response - no Median or CI possible to calculate
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Time to First at Least 35% Reduction in Spleen Volume From Baseline by Treatment (Primary Analysis)
24 weeks
|
0.67 probability of response
Interval 0.54 to 0.76
|
1 probability of response
There was only one BAT patient responder (≥ 35% reduction in spleen volume) but no consecutive readings to determine any value for duration of response - no Median or CI possible to calculate
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Time to First at Least 35% Reduction in Spleen Volume From Baseline by Treatment (Primary Analysis)
36 weeks
|
0.87 probability of response
Interval 0.76 to 0.93
|
1 probability of response
There was only one BAT patient responder (≥ 35% reduction in spleen volume) but no consecutive readings to determine any value for duration of response - no Median or CI possible to calculate
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Time to First at Least 35% Reduction in Spleen Volume From Baseline by Treatment (Primary Analysis)
48 weeks
|
0.97 probability of response
Interval 0.89 to 0.99
|
1 probability of response
There was only one BAT patient responder (≥ 35% reduction in spleen volume) but no consecutive readings to determine any value for duration of response - no Median or CI possible to calculate
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Time from randomization and the earliest of either increase in spleen volume >=25% from on-study nadir, splenic irradiation, splenectomy, leukemic transformation or deathPopulation: Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. Treatment groups were defined according to the treatment assignment at the time of randomization.
Median of time progression free survival (95% CI), years
Outcome measures
| Measure |
Ruxolitinib
n=146 Participants
5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
|
Best Available Therapy (BAT)
n=73 Participants
Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
|
Ruxolitinib - Grade 2
|
Ruxolitinib - Grade 3
|
Ruxolitinib - Missing
|
Best Available Therapy (BAT) - Grade 0
|
Best Available Therapy (BAT) - Grade 1
|
Best Available Therapy (BAT) - Grade 2
|
Best Available Therapy (BAT) - Grade 3
|
Best Available Therapy - Missing
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Progression-free Survival (PFS)
|
1.6 years
Interval 1.2 to 2.3
|
1.4 years
Interval 1.1 to 1.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Time from randomization and earliest of either leukemia or deathPopulation: Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. Treatment groups were defined according to the treatment assignment at the time of randomization.
Time from randomization and earliest of either (1) date of bone marrow blast count of 20% or greater; (2) date of first peripheral blast count of 20% or greater that was subsequently confirmed to sustain for at least 8 weeks; (3) date of death from any cause
Outcome measures
| Measure |
Ruxolitinib
n=146 Participants
5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
|
Best Available Therapy (BAT)
n=73 Participants
Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
|
Ruxolitinib - Grade 2
|
Ruxolitinib - Grade 3
|
Ruxolitinib - Missing
|
Best Available Therapy (BAT) - Grade 0
|
Best Available Therapy (BAT) - Grade 1
|
Best Available Therapy (BAT) - Grade 2
|
Best Available Therapy (BAT) - Grade 3
|
Best Available Therapy - Missing
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Leukemia-free Survival (LFS)
|
NA Years
Values are not estimable as Median was not reached
|
4.1 Years
Interval 2.4 to
Upper limit was not estimable
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From randomization until death from any causePopulation: Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. Treatment groups were defined according to the treatment assignment at the time of randomization.
Defined as the interval between randomization and the date of the bone marrow blast count of 20% or greater OR the date of the first peripheral blast count of 20% or greater that was subsequently confirmed to have been sustained for at least 8 weeks OR the date of death from any cause, whichever occurs first. OS was summarized using Kaplan-Meier estimates for each treatment arm. The estimates were supplemented by tables of number of events and probability estimates at several timepoints
Outcome measures
| Measure |
Ruxolitinib
n=146 Participants
5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
|
Best Available Therapy (BAT)
n=73 Participants
Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
|
Ruxolitinib - Grade 2
|
Ruxolitinib - Grade 3
|
Ruxolitinib - Missing
|
Best Available Therapy (BAT) - Grade 0
|
Best Available Therapy (BAT) - Grade 1
|
Best Available Therapy (BAT) - Grade 2
|
Best Available Therapy (BAT) - Grade 3
|
Best Available Therapy - Missing
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Survival (OS)
|
NA Years
Values are not estimable as Median was not reached
|
4.1 Years
Interval 2.4 to
Upper limit of CI was not estimable
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 48 weeksPopulation: Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria.
This was noted as fibrosis density and was tabulated by fibrosis grade at baseline and at week 48 (post-baseline). Descriptive statistics (participant percentages) were used. Fibrosis grades: 0 Scattered linear reticulin with no intersections corresponding to normal bone marrow ; 1 Loose network of reticulin with many intersections, especially in perivascular areas; 2 Diffuse and dense increase in reticulin with extensive intersections, occasionally with only focal bundles of collagen and/or focal osteosclerosis; 3 Diffuse and dense increase in reticulin with extensive intersections with coarse bundles of collagen, often associated with significant osteosclerosis
Outcome measures
| Measure |
Ruxolitinib
n=146 Participants
5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
|
Best Available Therapy (BAT)
n=73 Participants
Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
|
Ruxolitinib - Grade 2
|
Ruxolitinib - Grade 3
|
Ruxolitinib - Missing
|
Best Available Therapy (BAT) - Grade 0
|
Best Available Therapy (BAT) - Grade 1
|
Best Available Therapy (BAT) - Grade 2
|
Best Available Therapy (BAT) - Grade 3
|
Best Available Therapy - Missing
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Percentage of Participants With Bone Marrow Histomorphology at Week 48 (Primary Analysis)
Grade 1
|
7.5 Percentage of participants
|
2.7 Percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Participants With Bone Marrow Histomorphology at Week 48 (Primary Analysis)
Grade 2
|
8.9 Percentage of participants
|
6.8 Percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Participants With Bone Marrow Histomorphology at Week 48 (Primary Analysis)
Grade 0
|
2.7 Percentage of participants
|
0.0 Percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Participants With Bone Marrow Histomorphology at Week 48 (Primary Analysis)
Grade 3
|
24.0 Percentage of participants
|
15.1 Percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Participants With Bone Marrow Histomorphology at Week 48 (Primary Analysis)
Missing Grade
|
56.8 Percentage of participants
|
75.3 Percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, once a yearPopulation: Full Analysis Set (FAS) Numbers of Participants Analyzed reflect only those participants who were randomized to either Ruxolitinib or Best Available Therapy and do not count those participants who could have crossed over to Ruxolitinib
Shift table from baseline to last available postbaseline fibrosis grade by treatment The grade gives an indication of the activity or amount of inflammation and the stage represents the amount of fibrosis or scarring. The grade is assigned a number based on the degree of inflammation, which is usually scored from 0-4 with 0 being no activity and 3 or 4 considered severe activity
Outcome measures
| Measure |
Ruxolitinib
n=146 Participants
5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
|
Best Available Therapy (BAT)
n=146 Participants
Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
|
Ruxolitinib - Grade 2
n=146 Participants
|
Ruxolitinib - Grade 3
n=146 Participants
|
Ruxolitinib - Missing
n=146 Participants
|
Best Available Therapy (BAT) - Grade 0
n=73 Participants
|
Best Available Therapy (BAT) - Grade 1
n=73 Participants
|
Best Available Therapy (BAT) - Grade 2
n=73 Participants
|
Best Available Therapy (BAT) - Grade 3
n=73 Participants
|
Best Available Therapy - Missing
n=73 Participants
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Bone Marrow Histomorphology
Postbaseline Grade 3
|
0 participants
|
6 participants
|
19 participants
|
28 participants
|
2 participants
|
0 participants
|
0 participants
|
4 participants
|
8 participants
|
3 participants
|
|
Bone Marrow Histomorphology
Postbaseline Grade 0
|
1 participants
Interval 41.8 to 2.3
|
1 participants
Interval 47.9 to 1.9
|
2 participants
|
1 participants
|
2 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Bone Marrow Histomorphology
Postbaseline Grade 1
|
0 participants
|
10 participants
|
9 participants
|
2 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
1 participants
|
0 participants
|
|
Bone Marrow Histomorphology
Postbaseline Grade 2
|
0 participants
|
2 participants
|
8 participants
|
8 participants
|
1 participants
|
0 participants
|
0 participants
|
4 participants
|
1 participants
|
0 participants
|
|
Bone Marrow Histomorphology
Postbaseline Missing
|
2 participants
|
2 participants
|
17 participants
|
20 participants
|
3 participants
|
2 participants
|
2 participants
|
19 participants
|
24 participants
|
4 participants
|
SECONDARY outcome
Timeframe: baseline, 260 weeks (end of study)Population: Safety Set Numbers of Participants Analyzed reflect only those participants who were randomized to either Ruxolitinib or Best Available Therapy and do not count those participants who could have crossed over to Ruxolitinib
Number of Participants with duration of Follow up
Outcome measures
| Measure |
Ruxolitinib
n=146 Participants
5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
|
Best Available Therapy (BAT)
n=73 Participants
Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
|
Ruxolitinib - Grade 2
|
Ruxolitinib - Grade 3
|
Ruxolitinib - Missing
|
Best Available Therapy (BAT) - Grade 0
|
Best Available Therapy (BAT) - Grade 1
|
Best Available Therapy (BAT) - Grade 2
|
Best Available Therapy (BAT) - Grade 3
|
Best Available Therapy - Missing
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Duration of Follow-up by Treatment
<=1 year
|
16 participants
|
15 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Duration of Follow-up by Treatment
>1 year - <=2 years
|
21 participants
|
10 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Duration of Follow-up by Treatment
>2 years - <=3 years
|
9 participants
|
13 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Duration of Follow-up by Treatment
>3 years - <=4 years
|
12 participants
|
5 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Duration of Follow-up by Treatment
>4 years - <=5 years
|
27 participants
|
8 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Duration of Follow-up by Treatment
5 years
|
61 participants
|
22 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Ruxolitinib Randomized
Serious events: 51 serious events
Other events: 145 other events
Deaths: 0 deaths
Ruxolitinib Randomized + Extension Phase
Serious events: 85 serious events
Other events: 145 other events
Deaths: 0 deaths
BAT Randomized
Serious events: 22 serious events
Other events: 64 other events
Deaths: 0 deaths
Ruxolitinib Cross-over
Serious events: 20 serious events
Other events: 42 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ruxolitinib Randomized
n=146 participants at risk
Ruxolitinib Randomized
|
Ruxolitinib Randomized + Extension Phase
n=146 participants at risk
Ruxolitinib Randomized + Extension Phase
|
BAT Randomized
n=73 participants at risk
BAT Randomized
|
Ruxolitinib Cross-over
n=45 participants at risk
Ruxolitinib cross-over
|
|---|---|---|---|---|
|
Vascular disorders
Thrombosis
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Vascular disorders
Venous thrombosis
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Blood and lymphatic system disorders
Anaemia
|
5.5%
8/146
|
6.8%
10/146
|
5.5%
4/73
|
4.4%
2/45
|
|
Blood and lymphatic system disorders
Anaemia of chronic disease
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Blood and lymphatic system disorders
Coagulopathy
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Blood and lymphatic system disorders
Pancytopenia
|
1.4%
2/146
|
1.4%
2/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Blood and lymphatic system disorders
Paratracheal lymphadenopathy
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Blood and lymphatic system disorders
Splenic infarction
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Blood and lymphatic system disorders
Splenomegaly
|
0.00%
0/146
|
1.4%
2/146
|
1.4%
1/73
|
2.2%
1/45
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.68%
1/146
|
1.4%
2/146
|
1.4%
1/73
|
8.9%
4/45
|
|
Blood and lymphatic system disorders
Thrombotic microangiopathy
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Cardiac disorders
Acute coronary syndrome
|
0.68%
1/146
|
1.4%
2/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Cardiac disorders
Aortic valve stenosis
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Cardiac disorders
Arteriosclerosis coronary artery
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Cardiac disorders
Atrial fibrillation
|
0.68%
1/146
|
2.7%
4/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Cardiac disorders
Atrial flutter
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Cardiac disorders
Atrioventricular block
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Cardiac disorders
Cardiac arrest
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Cardiac disorders
Cardiac failure
|
2.1%
3/146
|
3.4%
5/146
|
1.4%
1/73
|
2.2%
1/45
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Cardiac disorders
Congestive cardiomyopathy
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Cardiac disorders
Coronary artery stenosis
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Cardiac disorders
Hypertensive heart disease
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Cardiac disorders
Ischaemic cardiomyopathy
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/146
|
1.4%
2/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Cardiac disorders
Right ventricular failure
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Cardiac disorders
Sick sinus syndrome
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Cardiac disorders
Stress cardiomyopathy
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/146
|
2.1%
3/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Eye disorders
Keratitis
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Eye disorders
Ocular vascular disorder
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Eye disorders
Visual impairment
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Abdominal pain
|
2.1%
3/146
|
4.1%
6/146
|
2.7%
2/73
|
2.2%
1/45
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Gastrointestinal disorders
Abdominal wall haematoma
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Anal fistula
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/146
|
0.68%
1/146
|
2.7%
2/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Colitis ischaemic
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Diarrhoea
|
1.4%
2/146
|
1.4%
2/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Enteritis
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Gastrointestinal disorders
Enterocolitis
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Gastrointestinal disorders
Faeces discoloured
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Gastrointestinal disorders
Gastric varices
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Gastrointestinal disorders
Gastritis haemorrhagic
|
0.68%
1/146
|
1.4%
2/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.68%
1/146
|
0.68%
1/146
|
1.4%
1/73
|
2.2%
1/45
|
|
Gastrointestinal disorders
Gastrointestinal ulcer
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Gastrointestinal disorders
Haematochezia
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Ileus paralytic
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Incarcerated umbilical hernia
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Intestinal perforation
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Oesophageal haemorrhage
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Peritoneal haemorrhage
|
0.00%
0/146
|
0.00%
0/146
|
2.7%
2/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Gastrointestinal disorders
Retroperitoneal haemorrhage
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Small intestinal perforation
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Subileus
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Gastrointestinal disorders
Umbilical hernia
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
1.4%
2/146
|
1.4%
2/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Gastrointestinal disorders
Varices oesophageal
|
2.1%
3/146
|
2.7%
4/146
|
0.00%
0/73
|
2.2%
1/45
|
|
General disorders
Asthenia
|
0.68%
1/146
|
0.68%
1/146
|
1.4%
1/73
|
0.00%
0/45
|
|
General disorders
Chest pain
|
0.68%
1/146
|
1.4%
2/146
|
0.00%
0/73
|
0.00%
0/45
|
|
General disorders
Disease progression
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
General disorders
General physical health deterioration
|
1.4%
2/146
|
2.7%
4/146
|
1.4%
1/73
|
0.00%
0/45
|
|
General disorders
Generalised oedema
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
General disorders
Inflammation
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
General disorders
Multi-organ failure
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
2.2%
1/45
|
|
General disorders
Oedema peripheral
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
2.2%
1/45
|
|
General disorders
Performance status decreased
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
General disorders
Pyrexia
|
2.7%
4/146
|
3.4%
5/146
|
1.4%
1/73
|
2.2%
1/45
|
|
Hepatobiliary disorders
Cholecystitis
|
1.4%
2/146
|
1.4%
2/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Hepatobiliary disorders
Hepatic failure
|
0.68%
1/146
|
1.4%
2/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Hepatobiliary disorders
Hepatomegaly
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Hepatobiliary disorders
Portal hypertension
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
0.68%
1/146
|
1.4%
2/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Infections and infestations
Bronchitis
|
2.1%
3/146
|
2.7%
4/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Infections and infestations
Campylobacter infection
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Infections and infestations
Cellulitis
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Infections and infestations
Clostridium difficile infection
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Cystitis
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Endocarditis
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Enterococcal sepsis
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Escherichia infection
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Escherichia urinary tract infection
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
4.4%
2/45
|
|
Infections and infestations
Febrile infection
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Gastroenteritis
|
1.4%
2/146
|
2.1%
3/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Gastroenteritis clostridial
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Infections and infestations
Gastroenteritis norovirus
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Gastrointestinal infection
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Genital infection female
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Infections and infestations
Herpes zoster
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Infection
|
0.00%
0/146
|
2.1%
3/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Infections and infestations
Influenza
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Klebsiella sepsis
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Infections and infestations
Lung infection
|
1.4%
2/146
|
1.4%
2/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Meningitis
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Meningoencephalitis herpetic
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Infections and infestations
Neutropenic sepsis
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Oesophageal infection
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Peritonitis
|
0.00%
0/146
|
1.4%
2/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Pneumocystis jirovecii pneumonia
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Pneumonia
|
1.4%
2/146
|
7.5%
11/146
|
5.5%
4/73
|
2.2%
1/45
|
|
Infections and infestations
Pneumonia mycoplasmal
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Postoperative abscess
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Pseudomonal sepsis
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Respiratory tract infection
|
1.4%
2/146
|
2.1%
3/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Sepsis
|
0.00%
0/146
|
1.4%
2/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Infections and infestations
Sepsis syndrome
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Septic shock
|
0.68%
1/146
|
1.4%
2/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Infections and infestations
Skin infection
|
0.68%
1/146
|
1.4%
2/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Soft tissue infection
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Staphylococcal infection
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Staphylococcal sepsis
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Testicular abscess
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Tuberculosis
|
0.68%
1/146
|
1.4%
2/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Urinary tract infection
|
0.68%
1/146
|
1.4%
2/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Infections and infestations
Urinary tract infection bacterial
|
1.4%
2/146
|
1.4%
2/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Urosepsis
|
0.68%
1/146
|
2.1%
3/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Infections and infestations
Viral infection
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Injury, poisoning and procedural complications
Concussion
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Injury, poisoning and procedural complications
Ear injury
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.68%
1/146
|
1.4%
2/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Injury, poisoning and procedural complications
Injury
|
0.68%
1/146
|
1.4%
2/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
0.00%
0/146
|
1.4%
2/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.68%
1/146
|
1.4%
2/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Injury, poisoning and procedural complications
Post-traumatic pain
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Injury, poisoning and procedural complications
Postoperative fever
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Injury, poisoning and procedural complications
Postoperative respiratory distress
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Injury, poisoning and procedural complications
Seroma
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Injury, poisoning and procedural complications
Thoracic vertebral fracture
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Injury, poisoning and procedural complications
Traumatic fracture
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Injury, poisoning and procedural complications
Traumatic haematoma
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Injury, poisoning and procedural complications
Traumatic intracranial haemorrhage
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Investigations
Alanine aminotransferase increased
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Investigations
Blood creatinine increased
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Investigations
C-reactive protein increased
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Investigations
Weight increased
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Metabolism and nutrition disorders
Fluid retention
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/146
|
2.1%
3/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Musculoskeletal and connective tissue disorders
Osteitis
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Musculoskeletal and connective tissue disorders
Osteolysis
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.68%
1/146
|
2.7%
4/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bowen's disease
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bronchial carcinoma
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Carcinoma in situ
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cholesteatoma
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Glioblastoma multiforme
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma recurrent
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.00%
0/146
|
0.68%
1/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to lymph nodes
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to peritoneum
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to spine
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic squamous cell carcinoma
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelofibrosis
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroendocrine carcinoma metastatic
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.68%
1/146
|
2.7%
4/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
|
2.1%
3/146
|
3.4%
5/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Nervous system disorders
Aphasia
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Nervous system disorders
Cerebral haemorrhage
|
1.4%
2/146
|
1.4%
2/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Nervous system disorders
Cerebrovascular accident
|
0.68%
1/146
|
2.7%
4/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Nervous system disorders
Coma
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Nervous system disorders
Convulsion
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Nervous system disorders
Epilepsy
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Nervous system disorders
Hepatic encephalopathy
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Nervous system disorders
Paraesthesia
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Nervous system disorders
Pseudoradicular syndrome
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Nervous system disorders
Somnolence
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Nervous system disorders
Syncope
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Psychiatric disorders
Abnormal behaviour
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Psychiatric disorders
Confusional state
|
0.68%
1/146
|
2.1%
3/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Psychiatric disorders
Delusion
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Psychiatric disorders
Depression
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Renal and urinary disorders
Hydronephrosis
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Renal and urinary disorders
Prerenal failure
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Renal and urinary disorders
Renal failure
|
0.68%
1/146
|
1.4%
2/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Renal and urinary disorders
Renal failure acute
|
2.1%
3/146
|
2.7%
4/146
|
1.4%
1/73
|
6.7%
3/45
|
|
Renal and urinary disorders
Renal failure chronic
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Renal and urinary disorders
Renal infarct
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Reproductive system and breast disorders
Uterine prolapse
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/146
|
0.00%
0/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.4%
2/146
|
2.7%
4/146
|
4.1%
3/73
|
0.00%
0/45
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.00%
0/146
|
1.4%
2/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Respiratory, thoracic and mediastinal disorders
Lung infiltration
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.68%
1/146
|
0.68%
1/146
|
1.4%
1/73
|
2.2%
1/45
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.00%
0/146
|
1.4%
2/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.68%
1/146
|
2.7%
4/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
2.2%
1/45
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/146
|
0.68%
1/146
|
2.7%
2/73
|
0.00%
0/45
|
|
Respiratory, thoracic and mediastinal disorders
Tachypnoea
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Skin and subcutaneous tissue disorders
Actinic keratosis
|
0.00%
0/146
|
0.00%
0/146
|
2.7%
2/73
|
0.00%
0/45
|
|
Vascular disorders
Aortic aneurysm
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Vascular disorders
Aortic thrombosis
|
0.00%
0/146
|
0.00%
0/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Vascular disorders
Arterial stenosis
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Vascular disorders
Circulatory collapse
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Vascular disorders
Hypertension
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Vascular disorders
Hypertensive crisis
|
0.68%
1/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
|
Vascular disorders
Intra-abdominal haematoma
|
0.00%
0/146
|
0.68%
1/146
|
0.00%
0/73
|
0.00%
0/45
|
Other adverse events
| Measure |
Ruxolitinib Randomized
n=146 participants at risk
Ruxolitinib Randomized
|
Ruxolitinib Randomized + Extension Phase
n=146 participants at risk
Ruxolitinib Randomized + Extension Phase
|
BAT Randomized
n=73 participants at risk
BAT Randomized
|
Ruxolitinib Cross-over
n=45 participants at risk
Ruxolitinib cross-over
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
41.8%
61/146
|
48.6%
71/146
|
11.0%
8/73
|
42.2%
19/45
|
|
Blood and lymphatic system disorders
Leukocytosis
|
4.8%
7/146
|
5.5%
8/146
|
0.00%
0/73
|
4.4%
2/45
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
45.9%
67/146
|
52.7%
77/146
|
13.7%
10/73
|
46.7%
21/45
|
|
Cardiac disorders
Angina pectoris
|
3.4%
5/146
|
5.5%
8/146
|
1.4%
1/73
|
4.4%
2/45
|
|
Cardiac disorders
Atrial fibrillation
|
1.4%
2/146
|
7.5%
11/146
|
1.4%
1/73
|
2.2%
1/45
|
|
Cardiac disorders
Palpitations
|
5.5%
8/146
|
8.2%
12/146
|
0.00%
0/73
|
4.4%
2/45
|
|
Cardiac disorders
Tachycardia
|
2.7%
4/146
|
5.5%
8/146
|
5.5%
4/73
|
2.2%
1/45
|
|
Ear and labyrinth disorders
Vertigo
|
3.4%
5/146
|
6.2%
9/146
|
1.4%
1/73
|
2.2%
1/45
|
|
Gastrointestinal disorders
Abdominal distension
|
4.8%
7/146
|
7.5%
11/146
|
4.1%
3/73
|
6.7%
3/45
|
|
Gastrointestinal disorders
Abdominal pain
|
9.6%
14/146
|
14.4%
21/146
|
16.4%
12/73
|
6.7%
3/45
|
|
Gastrointestinal disorders
Abdominal pain upper
|
8.2%
12/146
|
11.0%
16/146
|
5.5%
4/73
|
11.1%
5/45
|
|
Gastrointestinal disorders
Ascites
|
2.7%
4/146
|
4.1%
6/146
|
4.1%
3/73
|
6.7%
3/45
|
|
Gastrointestinal disorders
Constipation
|
8.2%
12/146
|
13.0%
19/146
|
4.1%
3/73
|
4.4%
2/45
|
|
Gastrointestinal disorders
Diarrhoea
|
24.7%
36/146
|
37.7%
55/146
|
17.8%
13/73
|
26.7%
12/45
|
|
Gastrointestinal disorders
Dyspepsia
|
4.8%
7/146
|
6.8%
10/146
|
5.5%
4/73
|
6.7%
3/45
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
2.7%
4/146
|
6.8%
10/146
|
0.00%
0/73
|
4.4%
2/45
|
|
Gastrointestinal disorders
Nausea
|
14.4%
21/146
|
20.5%
30/146
|
9.6%
7/73
|
11.1%
5/45
|
|
Gastrointestinal disorders
Vomiting
|
11.0%
16/146
|
18.5%
27/146
|
1.4%
1/73
|
8.9%
4/45
|
|
General disorders
Asthenia
|
19.2%
28/146
|
26.0%
38/146
|
12.3%
9/73
|
22.2%
10/45
|
|
General disorders
Chest pain
|
0.00%
0/146
|
0.00%
0/146
|
5.5%
4/73
|
8.9%
4/45
|
|
General disorders
Chills
|
2.7%
4/146
|
5.5%
8/146
|
0.00%
0/73
|
0.00%
0/45
|
|
General disorders
Fatigue
|
15.8%
23/146
|
24.7%
36/146
|
11.0%
8/73
|
17.8%
8/45
|
|
General disorders
General physical health deterioration
|
2.1%
3/146
|
4.8%
7/146
|
5.5%
4/73
|
6.7%
3/45
|
|
General disorders
Oedema peripheral
|
22.6%
33/146
|
37.7%
55/146
|
28.8%
21/73
|
17.8%
8/45
|
|
General disorders
Peripheral swelling
|
2.1%
3/146
|
4.8%
7/146
|
0.00%
0/73
|
6.7%
3/45
|
|
General disorders
Pyrexia
|
13.7%
20/146
|
24.7%
36/146
|
8.2%
6/73
|
15.6%
7/45
|
|
Infections and infestations
Bronchitis
|
10.3%
15/146
|
25.3%
37/146
|
6.8%
5/73
|
6.7%
3/45
|
|
Infections and infestations
Cystitis
|
6.2%
9/146
|
10.3%
15/146
|
4.1%
3/73
|
2.2%
1/45
|
|
Infections and infestations
Gastroenteritis
|
6.2%
9/146
|
9.6%
14/146
|
1.4%
1/73
|
2.2%
1/45
|
|
Infections and infestations
Herpes zoster
|
6.2%
9/146
|
11.0%
16/146
|
0.00%
0/73
|
11.1%
5/45
|
|
Infections and infestations
Lower respiratory tract infection
|
1.4%
2/146
|
1.4%
2/146
|
0.00%
0/73
|
6.7%
3/45
|
|
Infections and infestations
Nasopharyngitis
|
18.5%
27/146
|
27.4%
40/146
|
12.3%
9/73
|
8.9%
4/45
|
|
Infections and infestations
Respiratory tract infection
|
4.1%
6/146
|
6.2%
9/146
|
4.1%
3/73
|
4.4%
2/45
|
|
Infections and infestations
Rhinitis
|
4.8%
7/146
|
6.2%
9/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Infections and infestations
Upper respiratory tract infection
|
4.1%
6/146
|
6.2%
9/146
|
1.4%
1/73
|
4.4%
2/45
|
|
Infections and infestations
Urinary tract infection
|
7.5%
11/146
|
13.0%
19/146
|
2.7%
2/73
|
13.3%
6/45
|
|
Injury, poisoning and procedural complications
Fall
|
2.7%
4/146
|
5.5%
8/146
|
1.4%
1/73
|
2.2%
1/45
|
|
Investigations
Alanine aminotransferase increased
|
1.4%
2/146
|
2.1%
3/146
|
0.00%
0/73
|
6.7%
3/45
|
|
Investigations
Aspartate aminotransferase increased
|
0.68%
1/146
|
2.1%
3/146
|
0.00%
0/73
|
6.7%
3/45
|
|
Investigations
Blood alkaline phosphatase increased
|
2.1%
3/146
|
2.1%
3/146
|
0.00%
0/73
|
6.7%
3/45
|
|
Investigations
Cardiac murmur
|
4.1%
6/146
|
5.5%
8/146
|
4.1%
3/73
|
6.7%
3/45
|
|
Investigations
Gamma-glutamyltransferase increased
|
4.8%
7/146
|
7.5%
11/146
|
1.4%
1/73
|
2.2%
1/45
|
|
Investigations
Haemoglobin decreased
|
2.7%
4/146
|
4.1%
6/146
|
4.1%
3/73
|
8.9%
4/45
|
|
Investigations
Platelet count decreased
|
7.5%
11/146
|
8.2%
12/146
|
2.7%
2/73
|
20.0%
9/45
|
|
Investigations
Weight decreased
|
2.1%
3/146
|
5.5%
8/146
|
8.2%
6/73
|
4.4%
2/45
|
|
Investigations
Weight increased
|
15.8%
23/146
|
19.9%
29/146
|
1.4%
1/73
|
11.1%
5/45
|
|
Investigations
White blood cell count increased
|
2.1%
3/146
|
2.7%
4/146
|
0.00%
0/73
|
8.9%
4/45
|
|
Metabolism and nutrition disorders
Decreased appetite
|
4.1%
6/146
|
13.7%
20/146
|
5.5%
4/73
|
8.9%
4/45
|
|
Metabolism and nutrition disorders
Gout
|
0.68%
1/146
|
4.1%
6/146
|
1.4%
1/73
|
6.7%
3/45
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.68%
1/146
|
5.5%
8/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Metabolism and nutrition disorders
Iron overload
|
1.4%
2/146
|
3.4%
5/146
|
0.00%
0/73
|
6.7%
3/45
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
13.0%
19/146
|
20.5%
30/146
|
11.0%
8/73
|
15.6%
7/45
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.3%
18/146
|
16.4%
24/146
|
13.7%
10/73
|
6.7%
3/45
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
6.2%
9/146
|
6.2%
9/146
|
5.5%
4/73
|
4.4%
2/45
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
10.3%
15/146
|
19.2%
28/146
|
6.8%
5/73
|
8.9%
4/45
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
2.7%
4/146
|
5.5%
8/146
|
1.4%
1/73
|
6.7%
3/45
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
4.8%
7/146
|
7.5%
11/146
|
1.4%
1/73
|
2.2%
1/45
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
2.1%
3/146
|
6.2%
9/146
|
1.4%
1/73
|
2.2%
1/45
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
12.3%
18/146
|
16.4%
24/146
|
5.5%
4/73
|
24.4%
11/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
3.4%
5/146
|
7.5%
11/146
|
1.4%
1/73
|
2.2%
1/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
|
2.1%
3/146
|
6.8%
10/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Nervous system disorders
Dizziness
|
8.2%
12/146
|
13.7%
20/146
|
6.8%
5/73
|
13.3%
6/45
|
|
Nervous system disorders
Headache
|
12.3%
18/146
|
15.8%
23/146
|
5.5%
4/73
|
17.8%
8/45
|
|
Nervous system disorders
Paraesthesia
|
6.8%
10/146
|
11.0%
16/146
|
5.5%
4/73
|
8.9%
4/45
|
|
Nervous system disorders
Sciatica
|
3.4%
5/146
|
6.2%
9/146
|
1.4%
1/73
|
0.00%
0/45
|
|
Psychiatric disorders
Anxiety
|
3.4%
5/146
|
6.2%
9/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Psychiatric disorders
Insomnia
|
6.2%
9/146
|
8.9%
13/146
|
9.6%
7/73
|
11.1%
5/45
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
15.1%
22/146
|
26.0%
38/146
|
16.4%
12/73
|
20.0%
9/45
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
15.1%
22/146
|
24.0%
35/146
|
17.8%
13/73
|
26.7%
12/45
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
7.5%
11/146
|
8.9%
13/146
|
2.7%
2/73
|
2.2%
1/45
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
8.9%
13/146
|
12.3%
18/146
|
6.8%
5/73
|
13.3%
6/45
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
2.7%
4/146
|
5.5%
8/146
|
4.1%
3/73
|
4.4%
2/45
|
|
Respiratory, thoracic and mediastinal disorders
Rales
|
4.1%
6/146
|
5.5%
8/146
|
1.4%
1/73
|
4.4%
2/45
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
2.1%
3/146
|
5.5%
8/146
|
0.00%
0/73
|
8.9%
4/45
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.68%
1/146
|
2.1%
3/146
|
5.5%
4/73
|
8.9%
4/45
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
2.1%
3/146
|
7.5%
11/146
|
0.00%
0/73
|
2.2%
1/45
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
9.6%
14/146
|
18.5%
27/146
|
8.2%
6/73
|
8.9%
4/45
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.2%
9/146
|
11.6%
17/146
|
17.8%
13/73
|
8.9%
4/45
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.5%
8/146
|
8.2%
12/146
|
1.4%
1/73
|
4.4%
2/45
|
|
Skin and subcutaneous tissue disorders
Rosacea
|
1.4%
2/146
|
2.7%
4/146
|
1.4%
1/73
|
6.7%
3/45
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
1.4%
2/146
|
8.2%
12/146
|
0.00%
0/73
|
4.4%
2/45
|
|
Vascular disorders
Haematoma
|
10.3%
15/146
|
15.1%
22/146
|
4.1%
3/73
|
8.9%
4/45
|
|
Vascular disorders
Hypertension
|
5.5%
8/146
|
13.0%
19/146
|
4.1%
3/73
|
4.4%
2/45
|
Additional Information
Clinical Disclosure Office
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER