Trial Outcomes & Findings for A Study of the Efficacy and Safety of Tocilizumab in Participants With Systemic Sclerosis (SSc) (NCT NCT02453256)
NCT ID: NCT02453256
Last Updated: 2020-03-09
Results Overview
The efficacy of TCZ vs placebo is evaluated in terms of in mean change in mRSS. Skin thickness will be assessed by palpation and rated using an mRSS that ranges from 0 (normal) to 3 (severe skin thickening) across 17 different body sites. The total score is the sum of the individual skin scores from all of these sites and ranges from 0 to 51 units.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
212 participants
Primary outcome timeframe
From baseline to week 48
Results posted on
2020-03-09
Participant Flow
Overall 212 participants were randomized on to the study, 107 to the placebo arm and 105 to the tocilizumab arm. One participant in placebo arm withdrew consent prior to receiving any treatment and one participant in the tocilizumab arm was withdrawn due to randomization error prior to receiving any treatment.
Participant milestones
| Measure |
Double-Blind Placebo, Then Open Label Tocilizumab
Participants received double-blind matching placebo from Baseline to Week 48. Participants then received open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab, Then Open Label Tocilizumab
Participants received double-blind tocilizumab from Baseline to Week 48. Participants then received open-label tocilizumab from Weeks 48 to 96.
|
|---|---|---|
|
Double Blind Period
STARTED
|
106
|
104
|
|
Double Blind Period
COMPLETED
|
93
|
95
|
|
Double Blind Period
NOT COMPLETED
|
13
|
9
|
|
Open Label Period
STARTED
|
89
|
92
|
|
Open Label Period
COMPLETED
|
82
|
85
|
|
Open Label Period
NOT COMPLETED
|
7
|
7
|
Reasons for withdrawal
| Measure |
Double-Blind Placebo, Then Open Label Tocilizumab
Participants received double-blind matching placebo from Baseline to Week 48. Participants then received open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab, Then Open Label Tocilizumab
Participants received double-blind tocilizumab from Baseline to Week 48. Participants then received open-label tocilizumab from Weeks 48 to 96.
|
|---|---|---|
|
Double Blind Period
Death
|
1
|
1
|
|
Double Blind Period
Adverse Event
|
3
|
2
|
|
Double Blind Period
Withdrawal by Subject
|
9
|
5
|
|
Double Blind Period
Other
|
0
|
1
|
|
Open Label Period
Adverse Event
|
1
|
3
|
|
Open Label Period
Death
|
0
|
1
|
|
Open Label Period
Lost to Follow-up
|
1
|
0
|
|
Open Label Period
Other
|
0
|
2
|
|
Open Label Period
Withdrawal by Subject
|
5
|
1
|
Baseline Characteristics
A Study of the Efficacy and Safety of Tocilizumab in Participants With Systemic Sclerosis (SSc)
Baseline characteristics by cohort
| Measure |
Double-Blind Placebo, Then Tocilizumab Open Label
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants then received open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab, Then Tocilizumab Open Label
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants then received open-label tocilizumab from Weeks 48 to 96.
|
Total
n=210 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
49.3 Years
STANDARD_DEVIATION 12.6 • n=5 Participants
|
47.0 Years
STANDARD_DEVIATION 12.2 • n=7 Participants
|
48.2 Years
STANDARD_DEVIATION 12.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
90 Participants
n=5 Participants
|
81 Participants
n=7 Participants
|
171 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
26 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
79 Participants
n=5 Participants
|
89 Participants
n=7 Participants
|
168 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
9 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
90 Participants
n=5 Participants
|
85 Participants
n=7 Participants
|
175 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From baseline to week 48Population: The analysis was conducted in the Intent-to-treat (ITT) population, i.e. all patients who were randomized and received any study drug.
The efficacy of TCZ vs placebo is evaluated in terms of in mean change in mRSS. Skin thickness will be assessed by palpation and rated using an mRSS that ranges from 0 (normal) to 3 (severe skin thickening) across 17 different body sites. The total score is the sum of the individual skin scores from all of these sites and ranges from 0 to 51 units.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Change in Modified Rodnan Skin Score (mRSS) During Double-blind Period
|
-4.41 Units on a scale
Interval -5.96 to -2.86
|
-6.14 Units on a scale
Interval -7.71 to -4.57
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the Intent-to-treat (ITT) population, i.e. all patients who were randomized and received any study drug.
The proportion of participants with threshold improvements in mRSS at Week 48 relative to baseline.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Percentage of Participants With Greater Than or Equal to (>/=) 20%, 40%, or 60% Improvement in mRSS During Double-blind Period
≥ 20%
|
50.0 Percentage of Participants
Interval 40.01 to 59.99
|
72.1 Percentage of Participants
Interval 63.02 to 81.21
|
—
|
—
|
|
Percentage of Participants With Greater Than or Equal to (>/=) 20%, 40%, or 60% Improvement in mRSS During Double-blind Period
≥ 40%
|
37.7 Percentage of Participants
Interval 28.04 to 47.44
|
42.3 Percentage of Participants
Interval 32.33 to 52.28
|
—
|
—
|
|
Percentage of Participants With Greater Than or Equal to (>/=) 20%, 40%, or 60% Improvement in mRSS During Double-blind Period
≥ 60%
|
22.6 Percentage of Participants
Interval 14.2 to 31.08
|
17.3 Percentage of Participants
Interval 9.56 to 25.06
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to week 48Population: The analysis was conducted in the Intent-to-treat (ITT) population, i.e. all patients who were randomized and received any study drug.
FVC is pulmonary function test and will be conducted as per the study Pulmonary Function Manual, which is based on the American Thoracic Society/European Respiratory Society (ATS/ERS) Consensus Statement. FVC is the maximum amount of air exhaled from the lungs after taking the deepest breath possible. Patients perform three to eight exhalations into a spirometer with the highest value recorded.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Change From Baseline in Percent Predicted FVC (ppFVC) During Double-blind Period
|
-3.910 Percent Predicted FVC
Interval -4.82 to -1.62
|
-0.600 Percent Predicted FVC
Interval -2.38 to 0.88
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the Intent-to-treat (ITT) population, i.e. all patients who were randomized and received any study drug.
FVC is pulmonary function test and will be conducted as per the study Pulmonary Function Manual, which is based on the American Thoracic Society/European Respiratory Society (ATS/ERS) Consensus Statement. FVC is the maximum amount of air exhaled from the lungs after taking the deepest breath possible. Patients perform three to eight exhalations into a spirometer with the highest value recorded.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Change in Forced Vital Capacity (FVC) During Double-blind Period
|
-0.19 Liters of air
Interval -0.25 to -0.13
|
-0.02 Liters of air
Interval -0.09 to 0.04
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the Intent-to-treat (ITT) population, i.e. all patients who were randomized and received any study drug.
The Health Assessment Questionnaire Disability Index (HAQ-DI) consists of 20 questions referring to eight component sets consisting of dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Each item is scored on a 4-point scale from 0 to 3: 0 = Without any difficulty; 1 = With some difficulty; 2 = With much difficulty; 3 = Unable to do. Overall score was computed as the sum of component set scores and divided by the number of component sets answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. The total score indicates the patient's self-assessed level of disability. This outcome measure represents the change in mean score from baseline. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Change in Health Assessment Questionnaire Disability Index (HAQ-DI) Score During Double-blind Period
|
-0.06 Scores on a Scale
Interval -0.16 to 0.05
|
-0.11 Scores on a Scale
Interval -0.22 to -0.01
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the Intent-to-treat (ITT) population, i.e. all patients who were randomized and received any study drug.
The Patient's Global Assessment represents the patient's overall assessment of current SSc status on a 100-mm horizontal visual analogue scale (VAS), ranging from 0 on the extreme left end of the scale indicating "has no effect at all" (symptom free), and 100 on the extreme right end indicating "worst possible effect."
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Change in Patient Global Assessment Score During Double-blind Period
|
-7.66 mm
Interval -12.31 to -3.02
|
-10.10 mm
Interval -14.79 to -5.41
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the Intent-to-treat (ITT) population, i.e. all patients who were randomized and received any study drug.
The Physician's Global Assessment is to be completed on the basis of examination and overall assessment of the patient. The physician's assessment of the patient's SSc status will be scored on a 100-mm horizontal visual analogue scale (VAS), ranging from 0 on the extreme left end of the scale indicating "has no effect at all" (symptom free), and 100 on the extreme right end indicating "worst possible effect."
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Change in Physician Global Assessment Score During Double-blind Period
|
-19.99 mm
Interval -24.76 to -15.22
|
-22.45 mm
Interval -27.33 to -17.57
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the Intent-to-treat (ITT) population, i.e. all patients who were randomized and received any study drug.
Time to treatment failure is defined as the time from randomization to the time of death, decline in percent-predicted FVC \> 10% relative to baseline, \> 20% increase in mRSS and an increase in mRSS of equal to or more than 5 points, or occurrence of a predefined SSc-related complication as adjudicated by the Clinical Adjudication Committee (whichever occurs first) during the 48-week double-blind treatment period. The median TTF was not estimable and is not presented for either treatment arm because of the low number of patients with events at Week 48.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Time to Treatment Failure According to mRSS, FVC, or Protocol-Specified Event During Double-blind Period
|
NA months
Interval 48.7 to
The median and upper limit of CI were not evaluable because of the low number of participants with events at Week 48.
|
NA months
The median, lower limit and upper limit of CI were not evaluable because of the low number of participants with events at Week 48.
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline until Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Summary of key safety results including Adverse Events of Special Interest (AESI). All adverse events categorized according to MedDRA version 20.1. NMSC = Non-Melanoma Skin Cancer
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Summary of Adverse Events During Double-blind Period
AE related to study drug
|
34.9 Percentage of Participants
|
46.2 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
Related AE leading to withdrawal from treatment
|
1.9 Percentage of Participants
|
1.0 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
Related AE with dose modification/interruption
|
16.0 Percentage of Participants
|
11.5 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
Infections and Infestations SAE
|
6.6 Percentage of Participants
|
1.9 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
Infections and Infestations AE
|
50.0 Percentage of Participants
|
51.9 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
Opportunistic Infections and Infestations AE
|
0.9 Percentage of Participants
|
0.0 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
Malignancy AE
|
0.9 Percentage of Participants
|
1.9 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
Malignancy AE (excluding NMSC)
|
0.9 Percentage of Participants
|
1.9 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
At least one Hepatic SAE
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
At least one Stroke SAE
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
At least one Myocardial Infarction SAE
|
1.9 Percentage of Participants
|
0.0 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
At least one Anaphylactic Reaction AE
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
Anaphylactic Reaction AE (Sampson's Criteria)
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
At least one Gastrointestinal Perforation SAE
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
At least one Bleeding SAE
|
0.9 Percentage of Participants
|
0.0 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
At least one Demyelinating SAE
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
At least one Adverse Event (AE)
|
77.4 Percentage of Participants
|
85.6 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
Withdrawn from study due to an AE
|
3.8 Percentage of Participants
|
2.9 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
Fatal AE
|
2.8 Percentage of Participants
|
1.0 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
Serious Adverse Events (SAEs)
|
17.0 Percentage of Participants
|
12.5 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
SAE leading to withdrawal from treatment
|
3.8 Percentage of Participants
|
3.8 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
SAE leading to dose modification/interruption
|
6.6 Percentage of Participants
|
2.9 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
SAE related to study drug
|
6.6 Percentage of Participants
|
1.0 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
AE leading to withdrawal from treatment
|
10.4 Percentage of Participants
|
5.8 Percentage of Participants
|
—
|
—
|
|
Summary of Adverse Events During Double-blind Period
AE leading to dose modification/interruption
|
25.5 Percentage of Participants
|
19.2 Percentage of Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline until Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Adverse events listed according to MedDRA version 20.1 preferred terms and severity grade.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Incidence and Severity of Adverse Events During Double-blind Period
LOCALISED INFECTION GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LOCALISED INFECTION GRADE 2
|
2 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ORAL CANDIDIASIS GRADE 1
|
2 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PARONYCHIA GRADE 2
|
2 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PARONYCHIA GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
VULVOVAGINAL MYCOTIC INFECTION GRADE 2
|
2 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CANDIDA INFECTION GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CANDIDA INFECTION GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
FOLLICULITIS GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
FOLLICULITIS GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
GASTROINTESTINAL INFECTION GRADE 2
|
2 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HORDEOLUM GRADE 1
|
0 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
RHINITIS GRADE 2
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SOFT TISSUE INFECTION GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
TINEA PEDIS GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
TINEA PEDIS GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
VIRAL UPPER RESPIRATORY TRACT INFECTION GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
VIRAL UPPER RESPIRATORY TRACT INFECTION GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ABSCESS JAW GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ACUTE SINUSITIS GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BACTERAEMIA GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BODY TINEA GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CAMPYLOBACTER GASTROENTERITIS GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
GASTROENTERITIS VIRAL GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
GASTROINTESTINAL BACTERIAL OVERGROWTH GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
GASTROINTESTINAL VIRAL INFECTION GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
GINGIVITIS GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HERPES SIMPLEX GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INFECTIOUS MONONUCLEOSIS GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LARYNGITIS GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LICE INFESTATION GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
OESOPHAGEAL CANDIDIASIS GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ORAL HERPES GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
OSTEOMYELITIS GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PELVIC INFLAMMATORY DISEASE GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PERIODONTITIS GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PERIORBITAL CELLULITIS GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PHARYNGITIS STREPTOCOCCAL GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PULMONARY TUBERCULOSIS GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PULPITIS DENTAL GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PYELONEPHRITIS CHRONIC GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
WOUND INFECTION GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CYSTITIS GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SOFT TISSUE INFECTION GRADE 4
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BACK PAIN GRADE 2
|
4 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MUSCLE SPASMS GRADE 1
|
1 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MUSCLE SPASMS GRADE 2
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MUSCLE SPASMS GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PAIN IN EXTREMITY GRADE 1
|
2 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PAIN IN EXTREMITY GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PAIN IN EXTREMITY GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MYALGIA GRADE 2
|
3 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ARTHRITIS GRADE 2
|
2 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INTERVERTEBRAL DISC PROTRUSION GRADE 1
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INTERVERTEBRAL DISC PROTRUSION GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SPINAL OSTEOARTHRITIS GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
EXTREMITY CONTRACTURE GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
FLANK PAIN GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MYOPATHY GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
NECK PAIN GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PAIN IN JAW GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
POLYARTHRITIS GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
TENOSYNOVITIS GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
URTICARIA GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ALOPECIA GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SKIN OEDEMA GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CHRONIC GASTRITIS GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
OEDEMA PERIPHERAL GRADE 1
|
2 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
OEDEMA PERIPHERAL GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ASTHENIA GRADE 1
|
2 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INFLUENZA LIKE ILLNESS GRADE 1
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DEATH GRADE 5
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PERIPHERAL SWELLING GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PYREXIA GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SENSATION OF FOREIGN BODY GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
VESSEL PUNCTURE SITE PAIN GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ASPARTATE AMINOTRANSFERASE INCREASED GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
TRANSAMINASES INCREASED GRADE 2
|
2 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BLOOD CHOLESTEROL INCREASED GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BLOOD CREATINE PHOSPHOKINASE INCREASED GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LOW DENSITY LIPOPROTEIN INCREASED GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PROTEIN URINE PRESENT GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
UROBILINOGEN URINE INCREASED GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
WHITE BLOOD CELLS URINE POSITIVE GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INTERSTITIAL LUNG DISEASE GRADE 1
|
3 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INTERSTITIAL LUNG DISEASE GRADE 2
|
5 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DYSPNOEA GRADE 1
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DYSPNOEA GRADE 2
|
2 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HEADACHE GRADE 1
|
3 Number of participants
|
3 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HEADACHE GRADE 2
|
4 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
RADICULAR PAIN GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
NEUTROPENIA GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
WEIGHT FLUCTUATION GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PALPITATIONS GRADE 1
|
4 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PALPITATIONS GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SCLERODERMA RENAL CRISIS GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
AMENORRHOEA GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BREAST CYST GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PNEUMONIA GRADE 2
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PNEUMONITIS GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PNEUMONIA GRADE 3
|
3 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
RESPIRATORY TRACT INFECTION GRADE 1
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
RESPIRATORY TRACT INFECTION GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
RESPIRATORY TRACT INFECTION GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SINUSITIS GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SINUSITIS GRADE 2
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
NASOPHARYNGITIS GRADE 1
|
6 Number of participants
|
10 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
NASOPHARYNGITIS GRADE 2
|
2 Number of participants
|
3 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
URINARY TRACT INFECTION GRADE 1
|
5 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
URINARY TRACT INFECTION GRADE 2
|
5 Number of participants
|
3 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
URINARY TRACT INFECTION GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
GASTROENTERITIS GRADE 1
|
0 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
GASTROENTERITIS GRADE 2
|
2 Number of participants
|
4 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HERPES ZOSTER GRADE 2
|
5 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HERPES ZOSTER GRADE 3
|
0 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PHARYNGITIS GRADE 1
|
2 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PHARYNGITIS GRADE 2
|
2 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INFECTED SKIN ULCER GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ASTHENIA GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CALCINOSIS GRADE 1
|
1 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INJECTION SITE ERYTHEMA GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INJECTION SITE ERYTHEMA GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INJECTION SITE ERYTHEMA GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INJECTION SITE REACTION GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INJECTION SITE REACTION GRADE 2
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PAIN GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PAIN GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PAIN GRADE 4
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CHEST PAIN GRADE 1
|
2 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CYST GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CYST GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
FEELING HOT GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
GRANULOMA GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INJECTION SITE EXTRAVASATION GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INJECTION SITE INDURATION GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INJECTION SITE PRURITUS GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MALAISE GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
NODULE GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
WEIGHT DECREASED GRADE 1
|
3 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
WEIGHT DECREASED GRADE 2
|
3 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ALANINE AMINOTRANSFERASE INCREASED GRADE 1
|
0 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ALANINE AMINOTRANSFERASE INCREASED GRADE 2
|
2 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ALANINE AMINOTRANSFERASE INCREASED GRADE 3
|
0 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ASPARTATE AMINOTRANSFERASE INCREASED GRADE 1
|
0 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ASPARTATE AMINOTRANSFERASE INCREASED GRADE 2
|
2 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HEPATIC ENZYME INCREASED GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HEPATIC ENZYME INCREASED GRADE 2
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HEPATIC ENZYME INCREASED GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
WEIGHT INCREASED GRADE 1
|
2 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
TRANSAMINASES INCREASED GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BLOOD CHOLESTEROL INCREASED GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
UPPER RESPIRATORY TRACT INFECTION GRADE 1
|
4 Number of participants
|
7 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
UPPER RESPIRATORY TRACT INFECTION GRADE 2
|
7 Number of participants
|
4 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
UPPER RESPIRATORY TRACT INFECTION GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BLOOD CREATINE PHOSPHOKINASE INCREASED GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BLOOD BILIRUBIN INCREASED GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BLOOD URINE PRESENT GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CAROTID INTIMA-MEDIA THICKNESS INCREASED GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
COMPUTERISED TOMOGRAM THORAX ABNORMAL GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HAEMOGLOBIN DECREASED GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LIVER FUNCTION TEST ABNORMAL GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
TRANSFERRIN SATURATION INCREASED GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
TUBERCULIN TEST POSITIVE GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
URINE BILIRUBIN INCREASED GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
COUGH GRADE 1
|
3 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
COUGH GRADE 2
|
2 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
EPISTAXIS GRADE 1
|
3 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INFECTED SKIN ULCER GRADE 2
|
1 Number of participants
|
3 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
EPISTAXIS GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DYSPNOEA EXERTIONAL GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DYSPNOEA EXERTIONAL GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DYSPNOEA EXERTIONAL GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
OROPHARYNGEAL PAIN GRADE 1
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
OROPHARYNGEAL PAIN GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PRODUCTIVE COUGH GRADE 1
|
2 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DYSPHONIA GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HAEMOPTYSIS GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PAINFUL RESPIRATION GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PLEURAL EFFUSION GRADE 4
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
RHINITIS ALLERGIC GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
RHINORRHOEA GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INFECTED SKIN ULCER GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BRONCHITIS GRADE 1
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DIZZINESS GRADE 1
|
2 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DIZZINESS GRADE 2
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
NEUROPATHY PERIPHERAL GRADE 2
|
2 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
POST HERPETIC NEURALGIA GRADE 2
|
2 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CARPAL TUNNEL SYNDROME GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DYSGEUSIA GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HYPOAESTHESIA GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HYPOKINESIA GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MEMORY IMPAIRMENT GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
NERVE COMPRESSION GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
NEURALGIA GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PARAESTHESIA GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PARKINSONISM GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PRESYNCOPE GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SENSORY LOSS GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SOMNOLENCE GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LIMB INJURY GRADE 1
|
2 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LIMB INJURY GRADE 2
|
2 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LIMB INJURY GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
FALL GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
FALL GRADE 2
|
0 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
EAR INJURY GRADE 1
|
0 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LACERATION GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LACERATION GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SCAR GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SCAR GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
WOUND GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
WOUND GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ANIMAL BITE GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ANKLE FRACTURE GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ARTHROPOD STING GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CONTUSION GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CRANIOCEREBRAL INJURY GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
EXCORIATION GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
FACE INJURY GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INJURY CORNEAL GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
JOINT INJURY GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LIGAMENT SPRAIN GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LIMB TRAUMATIC AMPUTATION GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MENISCUS INJURY GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MUSCLE RUPTURE GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MUSCLE STRAIN GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ROAD TRAFFIC ACCIDENT GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SKIN ABRASION GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SPINAL COMPRESSION FRACTURE GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
THERMAL BURN GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ANAEMIA GRADE 1
|
3 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ANAEMIA GRADE 2
|
2 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ANAEMIA GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
IRON DEFICIENCY ANAEMIA GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
IRON DEFICIENCY ANAEMIA GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
IRON DEFICIENCY ANAEMIA GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LYMPHOPENIA GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LYMPHOPENIA GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
NEUTROPENIA GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ANAEMIA MEGALOBLASTIC GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
EOSINOPHILIA GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LEUKOCYTOSIS GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LEUKOPENIA GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LYMPHADENOPATHY MEDIASTINAL GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MICROANGIOPATHIC HAEMOLYTIC ANAEMIA GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MICROCYTIC ANAEMIA GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
THROMBOCYTOPENIA GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DECREASED APPETITE GRADE 1
|
4 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DYSLIPIDAEMIA GRADE 1
|
0 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DYSLIPIDAEMIA GRADE 2
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HYPERCHOLESTEROLAEMIA GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HYPERCHOLESTEROLAEMIA GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HYPERTRIGLYCERIDAEMIA GRADE 2
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DIABETES MELLITUS GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DIABETIC KETOACIDOSIS GRADE 4
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DIABETIC METABOLIC DECOMPENSATION GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
FOLATE DEFICIENCY GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
GOUT GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HYPERGLYCAEMIA GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HYPERLIPIDAEMIA GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HYPONATRAEMIA GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
IRON DEFICIENCY GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
OBESITY GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BUNDLE BRANCH BLOCK RIGHT GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BUNDLE BRANCH BLOCK RIGHT GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PERICARDIAL EFFUSION GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PERICARDIAL EFFUSION GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ACUTE MYOCARDIAL INFARCTION GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ANGINA PECTORIS GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ATRIAL FIBRILLATION GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ATRIAL TACHYCARDIA GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BRADYCARDIA GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CARDIAC FAILURE GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CARDIAC FAILURE CHRONIC GRADE 5
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MICROVASCULAR CORONARY ARTERY DISEASE GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MYOCARDIAL INFARCTION GRADE 5
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MYOCARDITIS GRADE 5
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PERICARDITIS GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SUPRAVENTRICULAR EXTRASYSTOLES GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
TACHYCARDIA GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ANXIETY GRADE 1
|
2 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ANXIETY GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INSOMNIA GRADE 1
|
2 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
STRESS GRADE 1
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ADJUSTMENT DISORDER GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DEPRESSED MOOD GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DEPRESSION GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
GENERALISED ANXIETY DISORDER GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SLEEP DISORDER GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CHALAZION GRADE 1
|
0 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
GLAUCOMA GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
GLAUCOMA GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BLEPHARITIS GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CATARACT GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CONJUNCTIVAL HAEMORRHAGE GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DRY EYE GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
EYELID OEDEMA GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
KERATITIS GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
VISUAL IMPAIRMENT GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
RAYNAUD'S PHENOMENON GRADE 1
|
1 Number of participants
|
3 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
RAYNAUD'S PHENOMENON GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BLOOD PRESSURE FLUCTUATION GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HYPERTENSION GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HYPOTENSION GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PERIPHERAL ISCHAEMIA GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
THROMBOPHLEBITIS GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
VASCULITIS GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ACUTE KIDNEY INJURY GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DYSURIA GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HAEMATURIA GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
NEPHROLITHIASIS GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
RENAL COLIC GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
RENAL CYST GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
RENAL PAIN GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CERVICAL POLYP GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ERECTILE DYSFUNCTION GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
GENITAL RASH GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MENSTRUATION IRREGULAR GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
OVARIAN CYST RUPTURED GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PENILE PAIN GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
B-CELL LYMPHOMA GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BENIGN BONE NEOPLASM GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BENIGN LUNG NEOPLASM GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BREAST CANCER GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LUNG ADENOCARCINOMA GRADE 4
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SKIN PAPILLOMA GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
FOOD ALLERGY GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HYPERSENSITIVITY GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
TYPE I HYPERSENSITIVITY GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MICROSTOMIA GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MICROSTOMIA GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PRESBYACUSIS GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
VERTIGO GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HYPOTHYROIDISM GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
THYROID MASS GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HEPATIC STEATOSIS GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
NEEDLE ISSUE GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CATARACT OPERATION GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BRONCHITIS GRADE 2
|
1 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INFLUENZA GRADE 1
|
1 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SINUSITIS GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
WOUND INFECTION GRADE 1
|
0 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
WOUND INFECTION GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CYSTITIS GRADE 2
|
0 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INFLUENZA GRADE 2
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LATENT TUBERCULOSIS GRADE 1
|
1 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LATENT TUBERCULOSIS GRADE 2
|
0 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
RASH PUSTULAR GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
RESPIRATORY TRACT INFECTION BACTERIAL GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SEPSIS GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SKIN BACTERIAL INFECTION GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
TONSILLITIS GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
TOOTH INFECTION GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
VIRAL INFECTION GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
WOUND INFECTION STAPHYLOCOCCAL GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ARTHRALGIA GRADE 1
|
3 Number of participants
|
8 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ARTHRALGIA GRADE 2
|
8 Number of participants
|
3 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ARTHRALGIA GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BACK PAIN GRADE 1
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MUSCULOSKELETAL PAIN GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MUSCULOSKELETAL PAIN GRADE 2
|
4 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BURSITIS GRADE 1
|
3 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BURSITIS GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MYALGIA GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MYOSITIS GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MYOSITIS GRADE 2
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
OSTEOCHONDROSIS GRADE 1
|
1 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
FOOT DEFORMITY GRADE 1
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SCLERODERMA GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SCLERODERMA GRADE 4
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SJOGREN'S SYNDROME GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SJOGREN'S SYNDROME GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SPINAL OSTEOARTHRITIS GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
FIBROMYALGIA GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
JOINT STIFFNESS GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
JOINT SWELLING GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MUSCLE CONTRACTURE GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MUSCLE FATIGUE GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MUSCULAR WEAKNESS GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MUSCULOSKELETAL CHEST PAIN GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
OSTEOPENIA GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
OSTEOPOROSIS GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
OSTEOPOROTIC FRACTURE GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
TENOSYNOVITIS STENOSANS GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SKIN ULCER GRADE 1
|
5 Number of participants
|
8 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SKIN ULCER GRADE 2
|
7 Number of participants
|
5 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SKIN ULCER GRADE 3
|
0 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PRURITUS GRADE 1
|
2 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PRURITUS GRADE 2
|
2 Number of participants
|
5 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
RASH GRADE 1
|
4 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
RASH GRADE 2
|
3 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ERYTHEMA GRADE 1
|
1 Number of participants
|
4 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ECZEMA GRADE 1
|
0 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ECZEMA GRADE 2
|
2 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ROSACEA GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ROSACEA GRADE 2
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SKIN TIGHTNESS GRADE 1
|
2 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DERMATITIS CONTACT GRADE 2
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INGROWING NAIL GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
INGROWING NAIL GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
MACULE GRADE 1
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
NIGHT SWEATS GRADE 1
|
2 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SKIN DISCOLOURATION GRADE 1
|
0 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SKIN FISSURES GRADE 1
|
0 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SKIN HYPERTROPHY GRADE 1
|
0 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SKIN INDURATION GRADE 1
|
2 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
URTICARIA GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
BLISTER GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CHLOASMA GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
COLD SWEAT GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DECUBITUS ULCER GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DERMATITIS ACNEIFORM GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DERMATITIS ATOPIC GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DIGITAL PITTING SCAR GRADE 4
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DRY SKIN GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ECCHYMOSIS GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
EXCESSIVE GRANULATION TISSUE GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HYPERTRICHOSIS GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ONYCHOLYSIS GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PAIN OF SKIN GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PAPULE GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
RASH ERYTHEMATOUS GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
RASH MACULO-PAPULAR GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SKIN DEPIGMENTATION GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SKIN FIBROSIS GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SKIN HYPOPIGMENTATION GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
VITILIGO GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DIARRHOEA GRADE 1
|
5 Number of participants
|
6 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DIARRHOEA GRADE 2
|
3 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
GASTROOESOPHAGEAL REFLUX DISEASE GRADE 1
|
3 Number of participants
|
3 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
GASTROOESOPHAGEAL REFLUX DISEASE GRADE 2
|
2 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
NAUSEA GRADE 1
|
5 Number of participants
|
3 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
NAUSEA GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ABDOMINAL PAIN GRADE 1
|
3 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ABDOMINAL PAIN GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ABDOMINAL PAIN GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CONSTIPATION GRADE 1
|
2 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
CONSTIPATION GRADE 2
|
2 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DYSPEPSIA GRADE 1
|
1 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DYSPEPSIA GRADE 2
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DYSPHAGIA GRADE 1
|
2 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DYSPHAGIA GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
STOMATITIS GRADE 1
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
STOMATITIS GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
VOMITING GRADE 1
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
VOMITING GRADE 3
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ABDOMINAL DISCOMFORT GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ABDOMINAL DISCOMFORT GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ABDOMINAL DISTENSION GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ABDOMINAL DISTENSION GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ABDOMINAL PAIN UPPER GRADE 1
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DENTAL CARIES GRADE 2
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
FAECES SOFT GRADE 1
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HAEMORRHOIDS GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HAEMORRHOIDS GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
TOOTHACHE GRADE 2
|
2 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ANAL HAEMORRHAGE GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DIVERTICULUM INTESTINAL GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DRY MOUTH GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
DUODENITIS GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
GASTRIC DISORDER GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
GASTRIC POLYPS GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
GASTRITIS GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
HAEMATOCHEZIA GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
ILEUS PARALYTIC GRADE 3
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
LOOSE TOOTH GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
OESOPHAGEAL DISORDER GRADE 1
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
OESOPHAGEAL HYPOMOTILITY GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PERIODONTAL DISEASE GRADE 2
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
PNEUMATOSIS INTESTINALIS GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
RANULA GRADE 1
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
SWOLLEN TONGUE GRADE 2
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
FATIGUE GRADE 1
|
3 Number of participants
|
7 Number of participants
|
—
|
—
|
|
Incidence and Severity of Adverse Events During Double-blind Period
FATIGUE GRADE 2
|
4 Number of participants
|
1 Number of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline up to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Reason of death is coded using MedDRA 20.1
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Number of Participants With Adverse Events Leading to Death During Double-blind Period
CARDIAC FAILURE CHRONIC
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Number of Participants With Adverse Events Leading to Death During Double-blind Period
MYOCARDITIS
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Number of Participants With Adverse Events Leading to Death During Double-blind Period
MYOCARDIAL INFARCTION
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Number of Participants With Adverse Events Leading to Death During Double-blind Period
DEATH
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline up to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Adverse event terms coded using MedDRA 20.1. Includes only those serious events adjudicated as SSC-related complications by an independent external committee.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period
OSTEOMYELITIS
|
0 Number of Participants
|
1 Number of Participants
|
—
|
—
|
|
Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period
WOUND INFECTION
|
0 Number of Participants
|
1 Number of Participants
|
—
|
—
|
|
Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period
CARDIAC FAILURE
|
0 Number of Participants
|
1 Number of Participants
|
—
|
—
|
|
Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period
CARDIAC FAILURE CHRONIC
|
1 Number of Participants
|
0 Number of Participants
|
—
|
—
|
|
Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period
MICROVASCULAR CORONARY ARTERY DISEASE
|
1 Number of Participants
|
0 Number of Participants
|
—
|
—
|
|
Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period
MYOCARDITIS
|
1 Number of Participants
|
0 Number of Participants
|
—
|
—
|
|
Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period
INFECTED SKIN ULCER
|
1 Number of Participants
|
0 Number of Participants
|
—
|
—
|
|
Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period
ILEUS PARALYTIC
|
1 Number of Participants
|
0 Number of Participants
|
—
|
—
|
|
Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period
PAIN
|
1 Number of Participants
|
0 Number of Participants
|
—
|
—
|
|
Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period
WEIGHT DECREASED
|
0 Number of Participants
|
1 Number of Participants
|
—
|
—
|
|
Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period
SCLERODERMA
|
1 Number of Participants
|
0 Number of Participants
|
—
|
—
|
|
Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period
HYPOKINESIA
|
0 Number of Participants
|
1 Number of Participants
|
—
|
—
|
|
Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period
ADJUSTMENT DISORDER
|
1 Number of Participants
|
0 Number of Participants
|
—
|
—
|
|
Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period
SCLERODERMA RENAL CRISIS
|
0 Number of Participants
|
1 Number of Participants
|
—
|
—
|
|
Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period
DIGITAL PITTING SCAR
|
1 Number of Participants
|
0 Number of Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline up to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
A laboratory event occurred if the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grade for a post-baseline laboratory measurement increased from baseline.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period
Low Neutrophils, Segmented, Abs
|
2 Number of Participants
|
27 Number of Participants
|
—
|
—
|
|
Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period
High Alkaline Phosphatase
|
7 Number of Participants
|
1 Number of Participants
|
—
|
—
|
|
Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period
High SGPT/ALT
|
17 Number of Participants
|
32 Number of Participants
|
—
|
—
|
|
Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period
High SGOT/AST
|
17 Number of Participants
|
24 Number of Participants
|
—
|
—
|
|
Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period
Low Platelet
|
0 Number of Participants
|
9 Number of Participants
|
—
|
—
|
|
Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period
High Bilirubin
|
1 Number of Participants
|
13 Number of Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
A digital ulcer is defined as an ulcer at or distal to the MCP joint on either the dorsal or volar surface, with loss of surface epithelialization. This does not include fissures, cracks, or calcium extrusions from calcinosis cutis. The number of fingers (0-10) with digital ulcers and the number of digital (or finger) ulcers will be counted and recorded by the investigator.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period
Decrease by >4
|
0 Percentage of participants
|
0 Percentage of participants
|
—
|
—
|
|
Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period
No change
|
85.4 Percentage of participants
|
87.2 Percentage of participants
|
—
|
—
|
|
Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period
Increase by 1
|
3.4 Percentage of participants
|
5.3 Percentage of participants
|
—
|
—
|
|
Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period
Increase by 2
|
1.1 Percentage of participants
|
1.1 Percentage of participants
|
—
|
—
|
|
Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period
Increase by 3
|
0 Percentage of participants
|
0 Percentage of participants
|
—
|
—
|
|
Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period
Increase by 4
|
0 Percentage of participants
|
0 Percentage of participants
|
—
|
—
|
|
Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period
Increase by >4
|
1.1 Percentage of participants
|
0 Percentage of participants
|
—
|
—
|
|
Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period
Decrease by 1
|
3.4 Percentage of participants
|
4.3 Percentage of participants
|
—
|
—
|
|
Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period
Decrease by 2
|
3.4 Percentage of participants
|
0 Percentage of participants
|
—
|
—
|
|
Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period
Decrease by 3
|
0 Percentage of participants
|
1.1 Percentage of participants
|
—
|
—
|
|
Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period
Decrease by 4
|
1.1 Percentage of participants
|
0 Percentage of participants
|
—
|
—
|
|
Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period
Baseline missing
|
1.1 Percentage of participants
|
1.1 Percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: BaselinePopulation: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Incidence of anti-Tocilizumab at baseline
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Percentage of Participants With Positive Anti-Tocilizumab Assay Result at Baseline
|
5.9 Percentage of Participants
|
2.9 Percentage of Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Double-blind period (up to Week 48)Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Incidence of anti-Tocilizumab antibodies during the study relative to the prevalence of anti-Tocilizumab antibodies at baseline. Samples that are positive for anti-TCZ in the screening assay will be further analyzed by a confirmation assay to confirm specificity. If the confirmation assay is positive, two additional tests will be performed: a neutralizing assay for the ability to inhibit the activity of TCZ and a test for anti -TCZ of the IgE isotype.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline up to Week 48
Positive Anti-TCZ Assay
|
0.0 Percentage of Participants
|
2.9 Percentage of Participants
|
—
|
—
|
|
Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline up to Week 48
Positive Confirmation Assay
|
0.0 Percentage of Participants
|
1.0 Percentage of Participants
|
—
|
—
|
|
Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline up to Week 48
Positive Neutralizing Assay
|
0.0 Percentage of Participants
|
1.0 Percentage of Participants
|
—
|
—
|
|
Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline up to Week 48
Positive IgE Assay
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline; during Weeks 8, 16, 24, 36, 48, 96, and/or at treatment discontinuation (up to 96 weeks); and 8 weeks after treatment discontinuation (up to 104 weeks overall)Pre-specified analysis of the relationship between Anti-Tocilizumab Antibody status and safety, efficacy, and PK endpoints were not analyzed via subgroup analyses as there was only 1 patient with ADA-positive status.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Correlation Between Anti-Tocilizumab Antibody Status and Outcome Measures Pertaining to the Efficacy, Safety, and Pharmacokinetics of Tocilizumab
|
NA Units on a scale
Pre-specified analysis of the relationship between Anti-Tocilizumab Antibody status and safety, efficacy, and PK endpoints were not analyzed via subgroup analyses as there was only 1 patient with ADA-positive status.
|
NA Units on a scale
Pre-specified analysis of the relationship between Anti-Tocilizumab Antibody status and safety, efficacy, and PK endpoints were not analyzed via subgroup analyses as there was only 1 patient with ADA-positive status.
|
—
|
—
|
SECONDARY outcome
Timeframe: From Predose up to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Erythrocyte Sedimentation Rate (ESR) levels predose at baseline and at subsequent time points after initiation of study drug.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Erythrocyte Sedimentation Rate (ESR), Mean, From Baseline to Week 48
Baseline
|
34.72 mm/hr
Standard Deviation 18.49
|
34.83 mm/hr
Standard Deviation 16.29
|
—
|
—
|
|
Erythrocyte Sedimentation Rate (ESR), Mean, From Baseline to Week 48
Week 4
|
31.38 mm/hr
Standard Deviation 19.00
|
14.29 mm/hr
Standard Deviation 12.98
|
—
|
—
|
|
Erythrocyte Sedimentation Rate (ESR), Mean, From Baseline to Week 48
Week 24
|
28.49 mm/hr
Standard Deviation 20.86
|
8.46 mm/hr
Standard Deviation 8.63
|
—
|
—
|
|
Erythrocyte Sedimentation Rate (ESR), Mean, From Baseline to Week 48
Week 48
|
26.59 mm/hr
Standard Deviation 18.62
|
10.82 mm/hr
Standard Deviation 15.53
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Erythrocyte Sedimentation Rate (ESR) levels predose at baseline and at subsequent time points after initiation of study drug.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Erythrocyte Sedimentation Rate (ESR), Median, From Baseline to Week 48
Week 4
|
30.00 mm/hr
Interval 16.5 to 39.5
|
9.50 mm/hr
Interval 4.0 to 23.0
|
—
|
—
|
|
Erythrocyte Sedimentation Rate (ESR), Median, From Baseline to Week 48
Week 24
|
25.00 mm/hr
Interval 12.0 to 36.0
|
5.00 mm/hr
Interval 3.0 to 8.0
|
—
|
—
|
|
Erythrocyte Sedimentation Rate (ESR), Median, From Baseline to Week 48
Baseline
|
33.0 mm/hr
Interval 23.0 to 43.0
|
33.50 mm/hr
Interval 26.0 to 42.0
|
—
|
—
|
|
Erythrocyte Sedimentation Rate (ESR), Median, From Baseline to Week 48
Week 48
|
22.50 mm/hr
Interval 14.0 to 31.5
|
5.50 mm/hr
Interval 3.0 to 12.0
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48
Week 4
|
13.41 pg/mL
Standard Deviation 29.98
|
143.97 pg/mL
Standard Deviation 427.01
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48
Week 8
|
14.21 pg/mL
Standard Deviation 26.82
|
111.44 pg/mL
Standard Deviation 280.34
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48
Week 16
|
15.40 pg/mL
Standard Deviation 24.26
|
66.20 pg/mL
Standard Deviation 70.50
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48
Week 24
|
11.81 pg/mL
Standard Deviation 24.05
|
62.74 pg/mL
Standard Deviation 53.40
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48
Week 36
|
9.32 pg/mL
Standard Deviation 15.23
|
62.15 pg/mL
Standard Deviation 68.08
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48
Week 48
|
9.25 pg/mL
Standard Deviation 15.14
|
53.98 pg/mL
Standard Deviation 57.25
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48
Baseline
|
11.83 pg/mL
Standard Deviation 19.74
|
13.88 pg/mL
Standard Deviation 43.77
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48
Baseline
|
5.21 pg/mL
Interval 0.0 to 15.0
|
4.65 pg/mL
Interval 0.0 to 419.0
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48
Week 4
|
5.31 pg/mL
Interval 0.0 to 246.0
|
56.50 pg/mL
Interval 0.0 to 3260.0
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48
Week 8
|
5.15 pg/mL
Interval 0.0 to 214.0
|
58.65 pg/mL
Interval 0.0 to 2650.0
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48
Week 16
|
5.01 pg/mL
Interval 0.0 to 117.0
|
48.25 pg/mL
Interval 0.0 to 494.0
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48
Week 24
|
3.53 pg/mL
Interval 0.0 to 151.0
|
47.90 pg/mL
Interval 0.0 to 286.0
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48
Week 36
|
4.01 pg/mL
Interval 0.0 to 107.0
|
46.30 pg/mL
Interval 14.8 to 608.0
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48
Week 48
|
3.85 pg/mL
Interval 0.0 to 80.5
|
43.45 pg/mL
Interval 0.0 to 439.0
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48
Week 24
|
0.13 pg/mL
Standard Deviation 30.63
|
53.33 pg/mL
Standard Deviation 46.81
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48
Week 36
|
-3.48 pg/mL
Standard Deviation 23.23
|
52.26 pg/mL
Standard Deviation 55.81
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48
Week 48
|
-1.60 pg/mL
Standard Deviation 21.54
|
40.01 pg/mL
Standard Deviation 29.89
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48
Week 4
|
1.11 pg/mL
Standard Deviation 28.78
|
130.60 pg/mL
Standard Deviation 395.93
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48
Week 8
|
2.43 pg/mL
Standard Deviation 31.00
|
97.22 pg/mL
Standard Deviation 237.43
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48
Week 16
|
3.07 pg/mL
Standard Deviation 31.71
|
57.10 pg/mL
Standard Deviation 62.62
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48
Week 4
|
-0.12 pg/mL
Interval -150.0 to 202.7
|
52.41 pg/mL
Interval -27.4 to 2841.0
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48
Week 8
|
0.83 pg/mL
Interval -148.6 to 210.5
|
52.35 pg/mL
Interval -9.8 to 2231.0
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48
Week 16
|
0.34 pg/mL
Interval -148.5 to 114.5
|
42.35 pg/mL
Interval -6.0 to 494.0
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48
Week 24
|
0.00 pg/mL
Interval -148.5 to 144.9
|
41.21 pg/mL
Interval -8.0 to 284.0
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48
Week 36
|
0.00 pg/mL
Interval -148.2 to 63.3
|
41.20 pg/mL
Interval 0.9 to 474.0
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48
Week 48
|
0.00 pg/mL
Interval -150.0 to 46.0
|
32.96 pg/mL
Interval -11.8 to 138.0
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Serum soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48
Baseline
|
42.16 ng/mL
Standard Deviation 32.41
|
42.22 ng/mL
Standard Deviation 14.56
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48
Week 4
|
46.07 ng/mL
Standard Deviation 73.52
|
486.58 ng/mL
Standard Deviation 122.94
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48
Week 8
|
45.71 ng/mL
Standard Deviation 57.95
|
546.59 ng/mL
Standard Deviation 142.58
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48
Week 16
|
47.81 ng/mL
Standard Deviation 68.22
|
583.87 ng/mL
Standard Deviation 164.36
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48
Week 24
|
41.35 ng/mL
Standard Deviation 15.17
|
587.28 ng/mL
Standard Deviation 153.90
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48
Week 36
|
38.13 ng/mL
Standard Deviation 11.22
|
589.59 ng/mL
Standard Deviation 140.63
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48
Week 48
|
49.27 ng/mL
Standard Deviation 76.97
|
571.48 ng/mL
Standard Deviation 167.85
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Serum soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48
Baseline
|
37.10 ng/mL
Interval 17.0 to 340.0
|
39.00 ng/mL
Interval 20.1 to 97.2
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48
Week 4
|
38.10 ng/mL
Interval 19.4 to 775.0
|
482.50 ng/mL
Interval 42.0 to 773.0
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48
Week 8
|
37.20 ng/mL
Interval 17.6 to 612.0
|
536.00 ng/mL
Interval 30.5 to 873.0
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48
Week 16
|
38.95 ng/mL
Interval 20.6 to 711.0
|
589.50 ng/mL
Interval 27.4 to 1290.0
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48
Week 24
|
39.30 ng/mL
Interval 19.5 to 99.8
|
590.00 ng/mL
Interval 23.2 to 945.0
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48
Week 36
|
36.20 ng/mL
Interval 21.1 to 67.5
|
591.00 ng/mL
Interval 45.4 to 970.0
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48
Week 48
|
36.00 ng/mL
Interval 19.2 to 596.0
|
576.50 ng/mL
Interval 23.4 to 973.0
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Serum soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48
Week 4
|
3.96 ng/mL
Standard Deviation 79.00
|
444.23 ng/mL
Standard Deviation 120.90
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48
Week 8
|
3.31 ng/mL
Standard Deviation 65.47
|
501.09 ng/mL
Standard Deviation 140.42
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48
Week 16
|
6.04 ng/mL
Standard Deviation 77.69
|
539.21 ng/mL
Standard Deviation 165.63
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48
Week 48
|
7.23 ng/mL
Standard Deviation 86.81
|
525.66 ng/mL
Standard Deviation 165.53
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48
Week 24
|
-1.29 ng/mL
Standard Deviation 35.46
|
540.98 ng/mL
Standard Deviation 152.70
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48
Week 36
|
-4.31 ng/mL
Standard Deviation 35.92
|
544.89 ng/mL
Standard Deviation 142.95
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Serum soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48
Week 4
|
0.20 ng/mL
Interval -318.4 to 709.5
|
437.80 ng/mL
Interval -13.4 to 724.3
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48
Week 8
|
0.20 ng/mL
Interval -305.9 to 560.8
|
489.90 ng/mL
Interval -14.1 to 823.0
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48
Week 16
|
0.25 ng/mL
Interval -316.4 to 679.0
|
542.30 ng/mL
Interval -28.0 to 1248.7
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48
Week 24
|
1.20 ng/mL
Interval -316.6 to 51.6
|
547.50 ng/mL
Interval -32.2 to 909.9
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48
Week 36
|
-0.40 ng/mL
Interval -315.7 to 24.1
|
541.70 ng/mL
Interval -26.6 to 942.9
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48
Week 48
|
-0.70 ng/mL
Interval -317.9 to 560.2
|
532.20 ng/mL
Interval -0.4 to 945.9
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline up to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Serum C-Reactive Protein (CRP) levels predose at baseline and at subsequent time points after initiation of study drug.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Serum C-Reactive Protein (CRP) Level, Mean, From Baseline to Week 48
Baseline
|
7.43 mg/L
Standard Deviation 12.61
|
9.00 mg/L
Standard Deviation 14.76
|
—
|
—
|
|
Serum C-Reactive Protein (CRP) Level, Mean, From Baseline to Week 48
Week 4
|
9.81 mg/L
Standard Deviation 20.79
|
0.85 mg/L
Standard Deviation 2.52
|
—
|
—
|
|
Serum C-Reactive Protein (CRP) Level, Mean, From Baseline to Week 48
Week 24
|
9.89 mg/L
Standard Deviation 13.99
|
0.56 mg/L
Standard Deviation 1.19
|
—
|
—
|
|
Serum C-Reactive Protein (CRP) Level, Mean, From Baseline to Week 48
Week 48
|
7.52 mg/L
Standard Deviation 12.80
|
1.58 mg/L
Standard Deviation 6.22
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline up to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Serum C-Reactive Protein (CRP) levels predose at baseline and at subsequent time points after initiation of study drug.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Serum C-Reactive Protein (CRP) Level, Median, From Baseline to Week 48
Week 48
|
3.67 mg/L
Interval 1.26 to 7.78
|
0.20 mg/L
Interval 0.2 to 0.59
|
—
|
—
|
|
Serum C-Reactive Protein (CRP) Level, Median, From Baseline to Week 48
Baseline
|
3.82 mg/L
Interval 1.19 to 8.69
|
4.05 mg/L
Interval 1.3 to 9.48
|
—
|
—
|
|
Serum C-Reactive Protein (CRP) Level, Median, From Baseline to Week 48
Week 4
|
3.71 mg/L
Interval 1.27 to 8.83
|
0.20 mg/L
Interval 0.2 to 0.5
|
—
|
—
|
|
Serum C-Reactive Protein (CRP) Level, Median, From Baseline to Week 48
Week 24
|
4.15 mg/L
Interval 1.43 to 13.1
|
0.20 mg/L
Interval 0.2 to 0.47
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The PK population includes all patients who received at least one TCZ injection and had at least one PK sample with detectable results.
Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter
Outcome measures
| Measure |
Double-Blind Placebo
n=103 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Serum Tocilizumab Concentration, Mean, From Baseline to Week 48
Baseline
|
0.00 ug/mL
Standard Deviation 0.03
|
—
|
—
|
—
|
|
Serum Tocilizumab Concentration, Mean, From Baseline to Week 48
Week 4
|
30.92 ug/mL
Standard Deviation 15.24
|
—
|
—
|
—
|
|
Serum Tocilizumab Concentration, Mean, From Baseline to Week 48
Week 8
|
41.82 ug/mL
Standard Deviation 17.66
|
—
|
—
|
—
|
|
Serum Tocilizumab Concentration, Mean, From Baseline to Week 48
Week 16
|
50.98 ug/mL
Standard Deviation 23.33
|
—
|
—
|
—
|
|
Serum Tocilizumab Concentration, Mean, From Baseline to Week 48
Week 24
|
54.34 ug/mL
Standard Deviation 26.24
|
—
|
—
|
—
|
|
Serum Tocilizumab Concentration, Mean, From Baseline to Week 48
Week 36
|
53.55 ug/mL
Standard Deviation 29.25
|
—
|
—
|
—
|
|
Serum Tocilizumab Concentration, Mean, From Baseline to Week 48
Week 48
|
54.67 ug/mL
Standard Deviation 29.79
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The PK population includes all patients who received at least one TCZ injection and had at least one PK sample with detectable results.
Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter
Outcome measures
| Measure |
Double-Blind Placebo
n=103 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Serum Tocilizumab Concentration, Median, From Baseline to Week 48
Baseline
|
0.00 ug/mL
Interval 0.0 to 0.2
|
—
|
—
|
—
|
|
Serum Tocilizumab Concentration, Median, From Baseline to Week 48
Week 4
|
28.70 ug/mL
Interval 0.4 to 86.8
|
—
|
—
|
—
|
|
Serum Tocilizumab Concentration, Median, From Baseline to Week 48
Week 8
|
39.25 ug/mL
Interval 8.3 to 97.6
|
—
|
—
|
—
|
|
Serum Tocilizumab Concentration, Median, From Baseline to Week 48
Week 16
|
47.40 ug/mL
Interval 9.5 to 120.0
|
—
|
—
|
—
|
|
Serum Tocilizumab Concentration, Median, From Baseline to Week 48
Week 24
|
52.60 ug/mL
Interval 7.6 to 117.0
|
—
|
—
|
—
|
|
Serum Tocilizumab Concentration, Median, From Baseline to Week 48
Week 36
|
52.50 ug/mL
Interval 4.0 to 138.0
|
—
|
—
|
—
|
|
Serum Tocilizumab Concentration, Median, From Baseline to Week 48
Week 48
|
52.10 ug/mL
Interval 0.4 to 145.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=30 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 16
|
17.9 Units on a scale
Standard Deviation 8.71
|
16.2 Units on a scale
Standard Deviation 5.58
|
—
|
—
|
|
Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 24
|
16.9 Units on a scale
Standard Deviation 9.38
|
14.7 Units on a scale
Standard Deviation 5.61
|
—
|
—
|
|
Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 36
|
16.2 Units on a scale
Standard Deviation 10.24
|
13.2 Units on a scale
Standard Deviation 4.97
|
—
|
—
|
|
Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 48
|
14.8 Units on a scale
Standard Deviation 9.89
|
12.2 Units on a scale
Standard Deviation 6.03
|
—
|
—
|
|
Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Baseline
|
20.4 Units on a scale
Standard Deviation 6.95
|
20.3 Units on a scale
Standard Deviation 5.56
|
—
|
—
|
|
Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 8
|
18.6 Units on a scale
Standard Deviation 7.78
|
17.9 Units on a scale
Standard Deviation 5.84
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=30 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Baseline
|
19.0 Units on a scale
Interval 10.0 to 40.0
|
20.0 Units on a scale
Interval 11.0 to 31.0
|
—
|
—
|
|
Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 8
|
18.0 Units on a scale
Interval 4.0 to 43.0
|
16.0 Units on a scale
Interval 9.0 to 34.0
|
—
|
—
|
|
Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 16
|
17.0 Units on a scale
Interval 0.0 to 38.0
|
15.0 Units on a scale
Interval 8.0 to 30.0
|
—
|
—
|
|
Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 24
|
16.0 Units on a scale
Interval 0.0 to 42.0
|
14.0 Units on a scale
Interval 6.0 to 29.0
|
—
|
—
|
|
Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 36
|
14.0 Units on a scale
Interval 0.0 to 47.0
|
13.5 Units on a scale
Interval 5.0 to 27.0
|
—
|
—
|
|
Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 48
|
14.0 Units on a scale
Interval 0.0 to 43.0
|
12.5 Units on a scale
Interval 2.0 to 30.0
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=29 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Baseline
|
20.4 Units on a scale
Standard Deviation 6.95
|
19.1 Units on a scale
Standard Deviation 6.24
|
—
|
—
|
|
Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 16
|
17.9 Units on a scale
Standard Deviation 8.71
|
16.2 Units on a scale
Standard Deviation 6.10
|
—
|
—
|
|
Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 48
|
14.8 Units on a scale
Standard Deviation 9.89
|
11.6 Units on a scale
Standard Deviation 5.72
|
—
|
—
|
|
Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 8
|
18.6 Units on a scale
Standard Deviation 7.78
|
17.2 Units on a scale
Standard Deviation 6.17
|
—
|
—
|
|
Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 24
|
16.9 Units on a scale
Standard Deviation 9.38
|
14.6 Units on a scale
Standard Deviation 6.66
|
—
|
—
|
|
Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 36
|
16.2 Units on a scale
Standard Deviation 10.24
|
13.4 Units on a scale
Standard Deviation 6.20
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=29 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Baseline
|
19.0 Units on a scale
Interval 10.0 to 40.0
|
18.0 Units on a scale
Interval 10.0 to 35.0
|
—
|
—
|
|
Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 16
|
17.0 Units on a scale
Interval 0.0 to 38.0
|
16.0 Units on a scale
Interval 5.0 to 27.0
|
—
|
—
|
|
Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 8
|
18.0 Units on a scale
Interval 4.0 to 43.0
|
17.0 Units on a scale
Interval 5.0 to 31.0
|
—
|
—
|
|
Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 24
|
16.0 Units on a scale
Interval 0.0 to 42.0
|
14.0 Units on a scale
Interval 3.0 to 28.0
|
—
|
—
|
|
Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 36
|
14.0 Units on a scale
Interval 0.0 to 47.0
|
13.0 Units on a scale
Interval 2.0 to 25.0
|
—
|
—
|
|
Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 48
|
14.0 Units on a scale
Interval 0.0 to 43.0
|
11.0 Units on a scale
Interval 0.0 to 24.0
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=29 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Baseline
|
20.4 Units on a scale
Standard Deviation 6.95
|
19.8 Units on a scale
Standard Deviation 6.82
|
—
|
—
|
|
Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 8
|
18.6 Units on a scale
Standard Deviation 7.78
|
17.9 Units on a scale
Standard Deviation 7.35
|
—
|
—
|
|
Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 36
|
16.2 Units on a scale
Standard Deviation 10.24
|
13.7 Units on a scale
Standard Deviation 7.07
|
—
|
—
|
|
Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 48
|
14.8 Units on a scale
Standard Deviation 9.89
|
12.8 Units on a scale
Standard Deviation 7.20
|
—
|
—
|
|
Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 16
|
17.9 Units on a scale
Standard Deviation 8.71
|
16.7 Units on a scale
Standard Deviation 7.31
|
—
|
—
|
|
Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 24
|
16.9 Units on a scale
Standard Deviation 9.38
|
15.6 Units on a scale
Standard Deviation 7.50
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=29 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Baseline
|
19.0 Units on a scale
Interval 10.0 to 40.0
|
19.0 Units on a scale
Interval 11.0 to 33.0
|
—
|
—
|
|
Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 8
|
18.0 Units on a scale
Interval 4.0 to 43.0
|
17.5 Units on a scale
Interval 5.0 to 32.0
|
—
|
—
|
|
Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 16
|
17.0 Units on a scale
Interval 0.0 to 38.0
|
15.0 Units on a scale
Interval 6.0 to 33.0
|
—
|
—
|
|
Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 24
|
16.0 Units on a scale
Interval 0.0 to 42.0
|
15.0 Units on a scale
Interval 2.0 to 31.0
|
—
|
—
|
|
Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 48
|
14.0 Units on a scale
Interval 0.0 to 43.0
|
11.0 Units on a scale
Interval 4.0 to 34.0
|
—
|
—
|
|
Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Week 36
|
14.0 Units on a scale
Interval 0.0 to 47.0
|
11.0 Units on a scale
Interval 4.0 to 30.0
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml.
Outcome measures
| Measure |
Double-Blind Placebo
n=92 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=30 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Change in Mean Modified Rodnan Skin Score (mRSS) at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48
Low Exposure
|
-5.3 Units on a scale
Standard Deviation 7.77
|
-8.0 Units on a scale
Standard Deviation 5.85
|
—
|
—
|
|
Change in Mean Modified Rodnan Skin Score (mRSS) at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48
Medium Exposure
|
-5.3 Units on a scale
Standard Deviation 7.77
|
-7.5 Units on a scale
Standard Deviation 5.06
|
—
|
—
|
|
Change in Mean Modified Rodnan Skin Score (mRSS) at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48
High Exposure
|
-5.3 Units on a scale
Standard Deviation 7.77
|
-7.0 Units on a scale
Standard Deviation 6.26
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml.
Outcome measures
| Measure |
Double-Blind Placebo
n=92 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=30 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Change in Median Modified Rodnan Skin Score (mRSS), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48
Medium Exposure
|
-5.5 Units on a scale
Interval -25.0 to 22.0
|
-7.0 Units on a scale
Interval -18.0 to 2.0
|
—
|
—
|
|
Change in Median Modified Rodnan Skin Score (mRSS), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48
Low Exposure
|
-5.5 Units on a scale
Interval -25.0 to 22.0
|
-8.0 Units on a scale
Interval -19.0 to 4.0
|
—
|
—
|
|
Change in Median Modified Rodnan Skin Score (mRSS), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48
High Exposure
|
-5.5 Units on a scale
Interval -25.0 to 22.0
|
-6.0 Units on a scale
Interval -20.0 to 6.0
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
In order to characterize exposure-efficacy relationships, ppFVC scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml.
Outcome measures
| Measure |
Double-Blind Placebo
n=91 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=29 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Change in Mean Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48
Low Exposure
|
-4.264 Percent
Standard Deviation 8.155
|
0.144 Percent
Standard Deviation 6.474
|
—
|
—
|
|
Change in Mean Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48
Medium Exposure
|
-4.264 Percent
Standard Deviation 8.155
|
-0.161 Percent
Standard Deviation 6.440
|
—
|
—
|
|
Change in Mean Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48
High Exposure
|
-4.264 Percent
Standard Deviation 8.155
|
-0.297 Percent
Standard Deviation 7.895
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 48Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
In order to characterize exposure-efficacy relationships, ppFVC scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml.
Outcome measures
| Measure |
Double-Blind Placebo
n=91 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=29 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Change in Median Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48
High Exposure
|
-3.910 Percent
Interval -31.47 to 13.47
|
0.000 Percent
Interval -10.55 to 19.69
|
—
|
—
|
|
Change in Median Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48
Low Exposure
|
-3.910 Percent
Interval -31.47 to 13.47
|
0.525 Percent
Interval -14.25 to 11.38
|
—
|
—
|
|
Change in Median Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48
Medium Exposure
|
-3.910 Percent
Interval -31.47 to 13.47
|
-1.600 Percent
Interval -13.83 to 17.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to Week 96Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Summary of key safety results including Adverse Events of Special Interest (AESI). All adverse events categorized according to MedDRA version 21.1. NMSC = Non-Melanoma Skin Cancer
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
n=89 Participants
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
n=92 Participants
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Summary of Adverse Events Up to Week 96
Serious Adverse Events (SAEs)
|
17.0 Percentage of participants
|
12.5 Percentage of participants
|
7.9 Percentage of participants
|
10.9 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
At least one Adverse Event (AE)
|
77.4 Percentage of participants
|
85.6 Percentage of participants
|
77.5 Percentage of participants
|
71.7 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
Withdrawn from study due to an AE
|
12.3 Percentage of participants
|
6.7 Percentage of participants
|
1.1 Percentage of participants
|
1.1 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
Fatal AE
|
2.8 Percentage of participants
|
1.0 Percentage of participants
|
1.1 Percentage of participants
|
1.1 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
SAE related to study drug
|
6.6 Percentage of participants
|
1.0 Percentage of participants
|
3.4 Percentage of participants
|
3.3 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
AE leading to withdrawal from treatment
|
12.3 Percentage of participants
|
6.7 Percentage of participants
|
1.1 Percentage of participants
|
1.1 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
Infections and Infestations AEs
|
50.0 Percentage of participants
|
52.9 Percentage of participants
|
46.1 Percentage of participants
|
39.1 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
Opportunistic Infections AEs
|
0.9 Percentage of participants
|
1.0 Percentage of participants
|
0 Percentage of participants
|
1.1 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
SAE leading to withdrawal from treatment
|
5.7 Percentage of participants
|
4.8 Percentage of participants
|
1.1 Percentage of participants
|
1.1 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
SAE leading to dose modification/interruption
|
5.7 Percentage of participants
|
2.9 Percentage of participants
|
4.5 Percentage of participants
|
3.3 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
AE leading to dose modification/interruption
|
26.4 Percentage of participants
|
19.2 Percentage of participants
|
28.1 Percentage of participants
|
22.8 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
AE related to study drug
|
34.0 Percentage of participants
|
46.2 Percentage of participants
|
33.7 Percentage of participants
|
34.8 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
Related AE leading to withdrawal from treatment
|
1.9 Percentage of participants
|
1.0 Percentage of participants
|
1.1 Percentage of participants
|
1.1 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
Related AE with dose modification/interruption
|
17.0 Percentage of participants
|
11.5 Percentage of participants
|
12.4 Percentage of participants
|
14.1 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
Serious Infections and Infestations AEs
|
6.6 Percentage of participants
|
1.9 Percentage of participants
|
3.4 Percentage of participants
|
1.1 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
Malignancy AEs
|
0.9 Percentage of participants
|
1.9 Percentage of participants
|
0 Percentage of participants
|
1.1 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
Malignancy AEs (excluding NMSC)
|
0.9 Percentage of participants
|
1.9 Percentage of participants
|
0 Percentage of participants
|
1.1 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
Serious Hepatic AEs
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
Serious Stroke AEs
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
Serious Myocardial Infarction AEs
|
1.9 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
Anaphylactic Reaction AEs
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
Anaphylactic Reaction AEs (Sampson's Criteria)
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
Serious Gastrointestinal Perforation AEs
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
Serious Bleeding AEs
|
0.9 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
|
Summary of Adverse Events Up to Week 96
Serious Demyelinating AEs
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
SECONDARY outcome
Timeframe: Up to Week 96Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) severity grade: 1 = mild, 2 = moderate, 3 = severe and/or requiring medical intervention but not life-threatening, 4 = life-threatening consequences, and 5 = death.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
n=89 Participants
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
n=92 Participants
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Incidence and Severity of Adverse Events Up to Week 96
Grade 1
|
61 Number of participants
|
78 Number of participants
|
60 Number of participants
|
53 Number of participants
|
|
Incidence and Severity of Adverse Events Up to Week 96
Grade 2
|
63 Number of participants
|
53 Number of participants
|
41 Number of participants
|
35 Number of participants
|
|
Incidence and Severity of Adverse Events Up to Week 96
Grade 3
|
21 Number of participants
|
18 Number of participants
|
9 Number of participants
|
8 Number of participants
|
|
Incidence and Severity of Adverse Events Up to Week 96
Grade 4
|
7 Number of participants
|
0 Number of participants
|
4 Number of participants
|
5 Number of participants
|
|
Incidence and Severity of Adverse Events Up to Week 96
Grade 5
|
3 Number of participants
|
1 Number of participants
|
1 Number of participants
|
1 Number of participants
|
SECONDARY outcome
Timeframe: Up to Week 96Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
n=89 Participants
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
n=92 Participants
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Number of Participants With Adverse Events Leading to Death Up to Week 96
MYOCARDIAL INFARCTION
|
1 Number of participants
|
0 Number of participants
|
0 Number of participants
|
0 Number of participants
|
|
Number of Participants With Adverse Events Leading to Death Up to Week 96
CARDIAC FAILURE CHRONIC
|
1 Number of participants
|
0 Number of participants
|
0 Number of participants
|
0 Number of participants
|
|
Number of Participants With Adverse Events Leading to Death Up to Week 96
MYOCARDITIS
|
1 Number of participants
|
0 Number of participants
|
0 Number of participants
|
0 Number of participants
|
|
Number of Participants With Adverse Events Leading to Death Up to Week 96
DEATH
|
0 Number of participants
|
1 Number of participants
|
0 Number of participants
|
0 Number of participants
|
|
Number of Participants With Adverse Events Leading to Death Up to Week 96
BRAIN INJURY
|
0 Number of participants
|
0 Number of participants
|
1 Number of participants
|
0 Number of participants
|
|
Number of Participants With Adverse Events Leading to Death Up to Week 96
PULMONARY HYPERTENSION
|
0 Number of participants
|
0 Number of participants
|
0 Number of participants
|
1 Number of participants
|
SECONDARY outcome
Timeframe: From Baseline to Week 96Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
A digital ulcer is defined as an ulcer at or distal to the MCP joint on either the dorsal or volar surface, with loss of surface epithelialization. This does not include fissures, cracks, or calcium extrusions from calcinosis cutis. The number of fingers (0-10) with digital ulcers and the number of digital (or finger) ulcers will be counted and recorded by the investigator.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
n=89 Participants
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
n=92 Participants
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Percentage of Participants With Change in Digital Ulcer Count at Week 96
No change
|
0 Percentage of participants
|
0 Percentage of participants
|
91.1 Percentage of participants
|
83.3 Percentage of participants
|
|
Percentage of Participants With Change in Digital Ulcer Count at Week 96
Increase by 1
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
4.8 Percentage of participants
|
|
Percentage of Participants With Change in Digital Ulcer Count at Week 96
Increase by 2
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
1.2 Percentage of participants
|
|
Percentage of Participants With Change in Digital Ulcer Count at Week 96
Increase by 3
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
1.2 Percentage of participants
|
|
Percentage of Participants With Change in Digital Ulcer Count at Week 96
Increase by 4
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
|
Percentage of Participants With Change in Digital Ulcer Count at Week 96
Increase by >4
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
1.2 Percentage of participants
|
|
Percentage of Participants With Change in Digital Ulcer Count at Week 96
Decrease by 1
|
0 Percentage of participants
|
0 Percentage of participants
|
3.8 Percentage of participants
|
4.8 Percentage of participants
|
|
Percentage of Participants With Change in Digital Ulcer Count at Week 96
Decrease by 2
|
0 Percentage of participants
|
0 Percentage of participants
|
2.5 Percentage of participants
|
0 Percentage of participants
|
|
Percentage of Participants With Change in Digital Ulcer Count at Week 96
Decrease by 3
|
0 Percentage of participants
|
0 Percentage of participants
|
1.3 Percentage of participants
|
1.2 Percentage of participants
|
|
Percentage of Participants With Change in Digital Ulcer Count at Week 96
Decrease by 4
|
0 Percentage of participants
|
0 Percentage of participants
|
1.3 Percentage of participants
|
1.2 Percentage of participants
|
|
Percentage of Participants With Change in Digital Ulcer Count at Week 96
Decrease by >4
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
|
Percentage of Participants With Change in Digital Ulcer Count at Week 96
Baseline missing
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
1.2 Percentage of participants
|
SECONDARY outcome
Timeframe: Open-label period from Week 48 to 96Population: Safety population: received at least one dose of study drug and provide data from at least one post dose safety assessment. Only samples from the Double Blind TCZ, then Open Label TCZ were measured by the lab after week 48. Data for the Double Blind Period were reported at the time of Primary Results disclosure up to Week 48.
Reported were the percentage of participants with post-baseline treatment-induced anti-TCZ antibodies. Positive samples underwent additional analyses: a neutralizing assay for the ability to inhibit the activity of TCZ and a test for anti -TCZ of the IgE isotype.
Outcome measures
| Measure |
Double-Blind Placebo
n=92 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline From Week 48 to 96
Treatment-Induced Anti-TCZ Antibodies
|
0.0 Percentage of Participants
|
—
|
—
|
—
|
|
Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline From Week 48 to 96
Anti-TCZ Antibodies of Neutralizing Potential
|
0.0 Percentage of Participants
|
—
|
—
|
—
|
|
Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline From Week 48 to 96
Anti-TCZ Antibodies of IgE
|
0.0 Percentage of Participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to Week 96Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Erythrocyte Sedimentation Rate (ESR) levels predose at baseline and at subsequent time points after initiation of study drug.
Outcome measures
| Measure |
Double-Blind Placebo
n=103 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=100 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
n=82 Participants
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
n=89 Participants
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Erythrocyte Sedimentation Rate (ESR) Up to Week 96
Week 4
|
31.38 mm/hr
Standard Deviation 19.00
|
14.29 mm/hr
Standard Deviation 12.98
|
—
|
—
|
|
Erythrocyte Sedimentation Rate (ESR) Up to Week 96
Baseline
|
34.72 mm/hr
Standard Deviation 18.49
|
34.83 mm/hr
Standard Deviation 16.29
|
—
|
—
|
|
Erythrocyte Sedimentation Rate (ESR) Up to Week 96
Week 24
|
28.49 mm/hr
Standard Deviation 20.86
|
8.46 mm/hr
Standard Deviation 8.63
|
—
|
—
|
|
Erythrocyte Sedimentation Rate (ESR) Up to Week 96
Week 48
|
26.23 mm/hr
Standard Deviation 18.53
|
10.89 mm/hr
Standard Deviation 15.39
|
—
|
—
|
|
Erythrocyte Sedimentation Rate (ESR) Up to Week 96
Week 72
|
—
|
—
|
9.54 mm/hr
Standard Deviation 9.47
|
8.29 mm/hr
Standard Deviation 10.13
|
|
Erythrocyte Sedimentation Rate (ESR) Up to Week 96
Week 96
|
—
|
—
|
9.67 mm/hr
Standard Deviation 8.67
|
8.06 mm/hr
Standard Deviation 8.86
|
SECONDARY outcome
Timeframe: Up to Week 96Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
n=79 Participants
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
n=79 Participants
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96
Baseline
|
11.85 pg/mL
Standard Deviation 19.73
|
13.86 pg/mL
Standard Deviation 43.78
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96
Week 4
|
13.41 pg/mL
Standard Deviation 29.98
|
144.75 pg/mL
Standard Deviation 429.14
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96
Week 8
|
14.21 pg/mL
Standard Deviation 26.82
|
111.44 pg/mL
Standard Deviation 280.34
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96
Week 16
|
15.40 pg/mL
Standard Deviation 24.26
|
66.20 pg/mL
Standard Deviation 70.50
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96
Week 24
|
11.81 pg/mL
Standard Deviation 24.05
|
62.74 pg/mL
Standard Deviation 53.40
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96
Week 36
|
9.32 pg/mL
Standard Deviation 15.23
|
62.15 pg/mL
Standard Deviation 68.08
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96
Week 48
|
9.10 pg/mL
Standard Deviation 14.88
|
53.34 pg/mL
Standard Deviation 56.80
|
—
|
—
|
|
Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96
Week 96
|
—
|
—
|
62.60 pg/mL
Standard Deviation 57.21
|
52.03 pg/mL
Standard Deviation 46.51
|
SECONDARY outcome
Timeframe: Up to Week 96Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Serum Soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug.
Outcome measures
| Measure |
Double-Blind Placebo
n=103 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=102 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
n=79 Participants
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
n=85 Participants
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96
Week 48
|
49.51 ng/mL
Standard Deviation 76.17
|
566.49 ng/mL
Standard Deviation 175.25
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96
Week 96
|
—
|
—
|
558.38 ng/mL
Standard Deviation 256.86
|
565.31 ng/mL
Standard Deviation 159.82
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96
Baseline
|
42.23 ng/mL
Standard Deviation 32.56
|
42.15 ng/mL
Standard Deviation 14.50
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96
Week 4
|
46.07 ng/mL
Standard Deviation 73.52
|
487.70 ng/mL
Standard Deviation 123.02
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96
Week 8
|
45.71 ng/mL
Standard Deviation 57.95
|
546.59 ng/mL
Standard Deviation 142.58
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96
Week 16
|
47.81 ng/mL
Standard Deviation 68.22
|
583.87 ng/mL
Standard Deviation 164.36
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96
Week 24
|
41.35 ng/mL
Standard Deviation 15.17
|
587.28 ng/mL
Standard Deviation 153.90
|
—
|
—
|
|
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96
Week 36
|
38.13 ng/mL
Standard Deviation 11.22
|
589.59 ng/mL
Standard Deviation 140.63
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline up to Week 96Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
Serum C-Reactive Protein (CRP) levels predose at baseline and at subsequent time points after initiation of study drug.
Outcome measures
| Measure |
Double-Blind Placebo
n=106 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 Participants
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
n=83 Participants
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
n=90 Participants
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96
Baseline
|
7.42 mg/L
Standard Deviation 12.62
|
8.99 mg/L
Standard Deviation 14.76
|
—
|
—
|
|
Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96
Week 4
|
10.05 mg/L
Standard Deviation 20.82
|
0.85 mg/L
Standard Deviation 2.50
|
—
|
—
|
|
Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96
Week 24
|
9.89 mg/L
Standard Deviation 13.99
|
0.56 mg/L
Standard Deviation 1.19
|
—
|
—
|
|
Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96
Week 48
|
7.40 mg/L
Standard Deviation 12.62
|
1.75 mg/L
Standard Deviation 6.43
|
—
|
—
|
|
Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96
Week 72
|
—
|
—
|
0.57 mg/L
Standard Deviation 0.80
|
0.92 mg/L
Standard Deviation 3.61
|
|
Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96
Week 96
|
—
|
—
|
0.90 mg/L
Standard Deviation 2.73
|
0.97 mg/L
Standard Deviation 5.08
|
SECONDARY outcome
Timeframe: Up to Week 96Population: The PK population included all participants who received at least one TCZ injection and had at least one PK sample with detectable results. Only samples from the Double Blind TCZ, then Open Label TCZ were measured by the lab after week 48. Data for the Double Blind Period were reported at the time of Primary Results disclosure up to Week 48.
Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter
Outcome measures
| Measure |
Double-Blind Placebo
n=101 Participants
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Serum Tocilizumab Concentration, Mean, Up to Week 96
Baseline
|
0.00 ug/mL
Standard Deviation 0.03
|
—
|
—
|
—
|
|
Serum Tocilizumab Concentration, Mean, Up to Week 96
Week 4
|
30.76 ug/mL
Standard Deviation 15.23
|
—
|
—
|
—
|
|
Serum Tocilizumab Concentration, Mean, Up to Week 96
Week 8
|
41.82 ug/mL
Standard Deviation 17.66
|
—
|
—
|
—
|
|
Serum Tocilizumab Concentration, Mean, Up to Week 96
Week 16
|
50.98 ug/mL
Standard Deviation 23.33
|
—
|
—
|
—
|
|
Serum Tocilizumab Concentration, Mean, Up to Week 96
Week 24
|
54.34 ug/mL
Standard Deviation 26.24
|
—
|
—
|
—
|
|
Serum Tocilizumab Concentration, Mean, Up to Week 96
Week 36
|
53.55 ug/mL
Standard Deviation 29.25
|
—
|
—
|
—
|
|
Serum Tocilizumab Concentration, Mean, Up to Week 96
Week 48
|
54.87 ug/mL
Standard Deviation 29.69
|
—
|
—
|
—
|
|
Serum Tocilizumab Concentration, Mean, Up to Week 96
Week 96
|
49.99 ug/mL
Standard Deviation 26.19
|
—
|
—
|
—
|
Adverse Events
Double-Blind Placebo
Serious events: 18 serious events
Other events: 59 other events
Deaths: 3 deaths
Double-Blind Tocilizumab
Serious events: 13 serious events
Other events: 60 other events
Deaths: 1 deaths
Placebo, Then Tocilizumab Open Label
Serious events: 7 serious events
Other events: 46 other events
Deaths: 1 deaths
Tocilizumab, Then Tocilizumab Open Label
Serious events: 10 serious events
Other events: 28 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Double-Blind Placebo
n=106 participants at risk
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 participants at risk
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
n=89 participants at risk
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
n=92 participants at risk
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
ANAEMIA MEGALOBLASTIC
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Blood and lymphatic system disorders
LYMPHADENOPATHY MEDIASTINAL
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Cardiac disorders
ANGINA PECTORIS
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.96%
1/104 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Cardiac disorders
ARRHYTHMIA
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/89 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
0.94%
1/106 • Number of events 2 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Cardiac disorders
CARDIAC FAILURE
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.96%
1/104 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Cardiac disorders
CARDIAC FAILURE CHRONIC
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Cardiac disorders
CARDIAC TAMPONADE
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/89 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Cardiac disorders
CARDIO-RESPIRATORY ARREST
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/89 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Cardiac disorders
CONGESTIVE CARDIOMYOPATHY
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/92 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Cardiac disorders
MICROVASCULAR CORONARY ARTERY DISEASE
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Cardiac disorders
MYOCARDIAL INFARCTION
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Cardiac disorders
MYOCARDITIS
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Eye disorders
RETINAL VEIN THROMBOSIS
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/92 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Gastrointestinal disorders
GASTRITIS EROSIVE
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/92 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Gastrointestinal disorders
ILEUS PARALYTIC
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Gastrointestinal disorders
RECTAL PROLAPSE
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/89 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
General disorders
DEATH
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.96%
1/104 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
General disorders
PAIN
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Infections and infestations
INFECTED SKIN ULCER
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Infections and infestations
INFECTIVE TENOSYNOVITIS
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/89 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Infections and infestations
OSTEOMYELITIS
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.96%
1/104 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Infections and infestations
OTITIS MEDIA
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/92 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Infections and infestations
PELVIC INFLAMMATORY DISEASE
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.96%
1/104 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Infections and infestations
PNEUMONIA
|
2.8%
3/106 • Number of events 3 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/89 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/92 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Infections and infestations
PYELONEPHRITIS CHRONIC
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Infections and infestations
RESPIRATORY TRACT INFECTION
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Infections and infestations
SEPSIS
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/89 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Infections and infestations
SOFT TISSUE INFECTION
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Infections and infestations
WOUND INFECTION
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.96%
1/104 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Injury, poisoning and procedural complications
FEMORAL NECK FRACTURE
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/89 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Injury, poisoning and procedural complications
LIMB TRAUMATIC AMPUTATION
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.96%
1/104 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Injury, poisoning and procedural complications
RADIUS FRACTURE
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/92 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Injury, poisoning and procedural complications
SPINAL CORD INJURY
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/92 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Investigations
WEIGHT DECREASED
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.96%
1/104 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Metabolism and nutrition disorders
DIABETIC KETOACIDOSIS
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Metabolism and nutrition disorders
HYPERGLYCAEMIA
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Musculoskeletal and connective tissue disorders
INTERVERTEBRAL DISC PROTRUSION
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/92 • Number of events 2 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Musculoskeletal and connective tissue disorders
JOINT STIFFNESS
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.96%
1/104 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Musculoskeletal and connective tissue disorders
SCLERODERMA
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Musculoskeletal and connective tissue disorders
TENDONITIS
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/89 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Musculoskeletal and connective tissue disorders
TENOSYNOVITIS
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/92 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Musculoskeletal and connective tissue disorders
TRIGGER FINGER
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/92 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-CELL LYMPHOMA
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.96%
1/104 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BENIGN BONE NEOPLASM
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BREAST CANCER
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.96%
1/104 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LUNG ADENOCARCINOMA
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/92 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Nervous system disorders
BRAIN INJURY
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/89 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Nervous system disorders
SYNCOPE
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/89 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Psychiatric disorders
ADJUSTMENT DISORDER
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Psychiatric disorders
DEPRESSION
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/89 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Renal and urinary disorders
ACUTE KIDNEY INJURY
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Renal and urinary disorders
NEPHROLITHIASIS
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.96%
1/104 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Renal and urinary disorders
SCLERODERMA RENAL CRISIS
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.96%
1/104 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMONIA ASPIRATION
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/89 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMOTHORAX
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/92 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY HYPERTENSION
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/92 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Skin and subcutaneous tissue disorders
DIGITAL PITTING SCAR
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Skin and subcutaneous tissue disorders
ECCHYMOSIS
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Skin and subcutaneous tissue disorders
RASH MACULO-PAPULAR
|
0.00%
0/106 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.96%
1/104 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Skin and subcutaneous tissue disorders
SKIN ULCER
|
0.94%
1/106 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/104 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
Other adverse events
| Measure |
Double-Blind Placebo
n=106 participants at risk
Participants received double-blind matching placebo from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Double-Blind Tocilizumab
n=104 participants at risk
Participants received double-blind tocilizumab from Baseline to Week 48. Participants may then receive open-label tocilizumab from Weeks 48 to 96.
|
Placebo, Then Tocilizumab Open Label
n=89 participants at risk
Participants who received placebo during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
Tocilizumab, Then Tocilizumab Open Label
n=92 participants at risk
Participants who received tocilizumab during the double blind period from Baseline to Week 48, received tocilizumab from Week 48 to Week 96.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
ANAEMIA
|
5.7%
6/106 • Number of events 6 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.9%
2/104 • Number of events 2 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/89 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/92 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Gastrointestinal disorders
DIARRHOEA
|
6.6%
7/106 • Number of events 7 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
5.8%
6/104 • Number of events 7 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
6.7%
6/89 • Number of events 7 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
5.4%
5/92 • Number of events 5 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Gastrointestinal disorders
GASTROOESOPHAGEAL REFLUX DISEASE
|
5.7%
6/106 • Number of events 6 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
3.8%
4/104 • Number of events 4 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
9.0%
8/89 • Number of events 8 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
2.2%
2/92 • Number of events 2 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Gastrointestinal disorders
NAUSEA
|
5.7%
6/106 • Number of events 6 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
2.9%
3/104 • Number of events 3 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
2.2%
2/89 • Number of events 2 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/92 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
General disorders
FATIGUE
|
6.6%
7/106 • Number of events 8 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
7.7%
8/104 • Number of events 9 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Infections and infestations
GASTROENTERITIS
|
1.9%
2/106 • Number of events 2 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
6.7%
7/104 • Number of events 7 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/89 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
3.3%
3/92 • Number of events 3 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Infections and infestations
NASOPHARYNGITIS
|
7.5%
8/106 • Number of events 9 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
12.5%
13/104 • Number of events 14 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
10.1%
9/89 • Number of events 10 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
4.3%
4/92 • Number of events 4 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
10.4%
11/106 • Number of events 15 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
11.5%
12/104 • Number of events 13 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
11.2%
10/89 • Number of events 16 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
4.3%
4/92 • Number of events 5 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Infections and infestations
URINARY TRACT INFECTION
|
9.4%
10/106 • Number of events 14 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
4.8%
5/104 • Number of events 5 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
7.9%
7/89 • Number of events 8 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/92 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Investigations
WEIGHT DECREASED
|
5.7%
6/106 • Number of events 6 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.9%
2/104 • Number of events 2 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/89 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
0.00%
0/92 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
13.2%
14/106 • Number of events 15 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
11.5%
12/104 • Number of events 14 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
3.4%
3/89 • Number of events 3 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
5.4%
5/92 • Number of events 5 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Nervous system disorders
HEADACHE
|
5.7%
6/106 • Number of events 6 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
2.9%
3/104 • Number of events 3 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/89 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/92 • Number of events 2 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
INTERSTITIAL LUNG DISEASE
|
7.5%
8/106 • Number of events 8 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.9%
2/104 • Number of events 2 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/89 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/92 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
3.8%
4/106 • Number of events 5 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
5.8%
6/104 • Number of events 6 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
2.2%
2/89 • Number of events 3 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.1%
1/92 • Number of events 1 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Skin and subcutaneous tissue disorders
RASH
|
6.6%
7/106 • Number of events 8 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
1.9%
2/104 • Number of events 2 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
3.4%
3/89 • Number of events 3 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
2.2%
2/92 • Number of events 2 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
|
Skin and subcutaneous tissue disorders
SKIN ULCER
|
11.3%
12/106 • Number of events 22 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
14.4%
15/104 • Number of events 28 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
18.0%
16/89 • Number of events 28 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
12.0%
11/92 • Number of events 22 • Up to Week 96
The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER