Trial Outcomes & Findings for Tocilizumab in the Treatment of Refractory Polymyositis and Dermatomyositis (NCT NCT02043548)
NCT ID: NCT02043548
Last Updated: 2020-10-30
Results Overview
The total improvement score was calculated by adding the improvement scores of all six core set measures based on 2016 American College of Rheumatology (ACR)/European League Against Rheumatism(EULAR) myositis response criteria. The minimum and maximum values of the average Total Improvement Scores are 0 and 100; The minimum and maximum values of the average Total Improvement Scores of our included patients are 5.0 and 67.1; The higher scores mean a better outcome.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
36 participants
Primary outcome timeframe
Week 4, 8, 12, 16, 20, and 24
Results posted on
2020-10-30
Participant Flow
Adult refractory dermatomyositis and polymyositis
Participant milestones
| Measure |
Group A: Tocilizumab
Tocilizumab will be given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
tocilizumab: given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
Group B: Placebo
Placebo arm - no active drug
placebo: given by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
|---|---|---|
|
Overall Study
STARTED
|
18
|
18
|
|
Overall Study
COMPLETED
|
17
|
17
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Group A: Tocilizumab
Tocilizumab will be given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
tocilizumab: given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
Group B: Placebo
Placebo arm - no active drug
placebo: given by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
|---|---|---|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
|
Overall Study
Adverse Event
|
0
|
1
|
Baseline Characteristics
Tocilizumab in the Treatment of Refractory Polymyositis and Dermatomyositis
Baseline characteristics by cohort
| Measure |
Group A: Tocilizumab
n=18 Participants
Tocilizumab will be given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
tocilizumab: given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
Group B: Placebo
n=18 Participants
Placebo arm - no active drug
placebo: given by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
Total
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
15 Participants
n=93 Participants
|
16 Participants
n=4 Participants
|
31 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
|
Age, Continuous
|
52.3 years
n=93 Participants
|
50.4 years
n=4 Participants
|
52.3 years
n=27 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=93 Participants
|
13 Participants
n=4 Participants
|
28 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
17 Participants
n=93 Participants
|
16 Participants
n=4 Participants
|
33 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
3 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
White
|
12 Participants
n=93 Participants
|
14 Participants
n=4 Participants
|
26 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Unknown or Not Reported
|
2 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Dermatomyositis vs. polymyositis per treatment group
Dermatomyositis
|
10 Participants
n=93 Participants
|
13 Participants
n=4 Participants
|
23 Participants
n=27 Participants
|
|
Dermatomyositis vs. polymyositis per treatment group
Polymyositis
|
8 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
13 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Week 4, 8, 12, 16, 20, and 24Population: All participants randomized are included in intention to treat analysis
The total improvement score was calculated by adding the improvement scores of all six core set measures based on 2016 American College of Rheumatology (ACR)/European League Against Rheumatism(EULAR) myositis response criteria. The minimum and maximum values of the average Total Improvement Scores are 0 and 100; The minimum and maximum values of the average Total Improvement Scores of our included patients are 5.0 and 67.1; The higher scores mean a better outcome.
Outcome measures
| Measure |
Group A: Tocilizumab
n=18 Participants
Tocilizumab will be given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
tocilizumab: given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
Group B: Placebo
n=18 Participants
Placebo arm - no active drug
placebo: given by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
|---|---|---|
|
Compare the Average Total Improvement Scores at Visits 2 Through 7 During the 6-month Treatment Period Between the Treatment and Placebo Arms
|
26.4 score on a scale
Standard Deviation 16.8
|
29.3 score on a scale
Standard Deviation 16.8
|
SECONDARY outcome
Timeframe: Week 4, 8, 12, 16, 20, and 24Time to achieve the first DOI between the treatment and placebo arms.The total improvement score (TIS) is the sum of all 6 improvement scores associated with the change in each core set measure. A TIS \>= 20 represents minimal improvement, a score of \>=40 represents moderate improvement, and a score of \>=60 represents major improvement.
Outcome measures
| Measure |
Group A: Tocilizumab
n=18 Participants
Tocilizumab will be given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
tocilizumab: given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
Group B: Placebo
n=18 Participants
Placebo arm - no active drug
placebo: given by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
|---|---|---|
|
Comparison of the Time to First Definition of Improvement (DOI) Between the 2 Arms
|
42.4 days
Interval 27.5 to 90.4
|
55.5 days
Interval 29.4 to 114.6
|
SECONDARY outcome
Timeframe: Week 4, 8, 12, 16, 20, and 24We compared the count of the adverse events between the treatment and placebo arms statistically.
Outcome measures
| Measure |
Group A: Tocilizumab
n=18 Participants
Tocilizumab will be given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
tocilizumab: given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
Group B: Placebo
n=18 Participants
Placebo arm - no active drug
placebo: given by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
|---|---|---|
|
Count of the Adverse Events Between the Treatment and Placebo Arms.
|
14 events
|
9 events
|
SECONDARY outcome
Timeframe: Week 4, 8, 12, 16, 20, and 24Population: Only 33 of the total 36 patients were included in analysis due to missing data on three participants.
Mean change of steroid dose prednisone equivalent from last visit to baseline visit was compared between the two treatment arms
Outcome measures
| Measure |
Group A: Tocilizumab
n=17 Participants
Tocilizumab will be given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
tocilizumab: given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
Group B: Placebo
n=16 Participants
Placebo arm - no active drug
placebo: given by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
|---|---|---|
|
Comparison of the Steroid-sparing Effect (Calculated Using Prednisone Dose Equivalents) Between the Treatment and Placebo Arms
|
0.0 mg
Interval 0.0 to 0.0
|
0.0 mg
Interval 0.0 to 5.0
|
SECONDARY outcome
Timeframe: Week 4, 8, 12, 16, 20, and 24The core set measure tested was manual muscle testing, and we compared the mean manual muscle test measures in subjects over time. The minimum and maximum values of the manual muscle testing are 0 and 150; The minimum and maximum values of the manual muscle testing of our included patients are 97.0 and 150.0; The higher scores mean a better outcome.
Outcome measures
| Measure |
Group A: Tocilizumab
n=18 Participants
Tocilizumab will be given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
tocilizumab: given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
Group B: Placebo
n=18 Participants
Placebo arm - no active drug
placebo: given by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
|---|---|---|
|
Comparison of Individual Average Core Set Measure in Subjects Over Time Between the 2 Arms (Repeated Measures Analysis)
|
130.7 score on a scale
Standard Deviation 16.94
|
137.3 score on a scale
Standard Deviation 11.83
|
SECONDARY outcome
Timeframe: Week 4, 8, 12, 16, 20, and 24Population: The total improvement score was calculated at each timepoint (weeks 4, 8, 12,16, 20 and 24) for each subject. The greatest improvement score achieved for each subject between week 4 through week 24 was reported (minimal, moderate or major improvement).
Compared the number of subjects meeting total improvement scores \>=20 (minimal) and \>=40 (moderate) and \>=60 (major) based on 2016 ACR EULAR myositis response criteria for treatment group and placebo group. The highest TIS score achieved from week 4 through week 24 was used to determine the effect size between both treatment arms.
Outcome measures
| Measure |
Group A: Tocilizumab
n=18 Participants
Tocilizumab will be given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
tocilizumab: given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
Group B: Placebo
n=18 Participants
Placebo arm - no active drug
placebo: given by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
|---|---|---|
|
Magnitude of the Effect Size Between the Both Treatment Arms
Minimal Improvement
|
3 participants
|
7 participants
|
|
Magnitude of the Effect Size Between the Both Treatment Arms
Moderate Improvement
|
4 participants
|
6 participants
|
|
Magnitude of the Effect Size Between the Both Treatment Arms
Major Improvement
|
3 participants
|
2 participants
|
Adverse Events
Group A: Tocilizumab
Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths
Group B: Placebo
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Group A: Tocilizumab
n=18 participants at risk
Tocilizumab will be given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
tocilizumab: given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
Group B: Placebo
n=18 participants at risk
Placebo arm - no active drug
placebo: given by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
|---|---|---|
|
Cardiac disorders
Bilateral sub-massive pulmonary embolism
|
5.6%
1/18 • Number of events 1 • Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.
|
0.00%
0/18 • Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.
|
Other adverse events
| Measure |
Group A: Tocilizumab
n=18 participants at risk
Tocilizumab will be given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
tocilizumab: given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
Group B: Placebo
n=18 participants at risk
Placebo arm - no active drug
placebo: given by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
|
|---|---|---|
|
Injury, poisoning and procedural complications
General disorders and administration site conditions
|
5.6%
1/18 • Number of events 1 • Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.
|
0.00%
0/18 • Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.
|
|
Infections and infestations
Sinusitis
|
22.2%
4/18 • Number of events 5 • Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.
|
16.7%
3/18 • Number of events 4 • Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.
|
|
Infections and infestations
Upper Respiratory Infection
|
16.7%
3/18 • Number of events 3 • Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.
|
5.6%
1/18 • Number of events 1 • Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.
|
|
Infections and infestations
Herpes Zoster
|
0.00%
0/18 • Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.
|
11.1%
2/18 • Number of events 2 • Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.
|
|
Psychiatric disorders
Depression
|
5.6%
1/18 • Number of events 1 • Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.
|
0.00%
0/18 • Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.
|
|
Skin and subcutaneous tissue disorders
pruritis
|
5.6%
1/18 • Number of events 1 • Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.
|
0.00%
0/18 • Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.
|
|
Vascular disorders
Hypertension
|
5.6%
1/18 • Number of events 1 • Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.
|
0.00%
0/18 • Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.
|
|
Musculoskeletal and connective tissue disorders
Muscle Cramps
|
0.00%
0/18 • Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.
|
5.6%
1/18 • Number of events 1 • Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.
|
|
Nervous system disorders
Headache
|
0.00%
0/18 • Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.
|
5.6%
1/18 • Number of events 1 • Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place