Trial Outcomes & Findings for Rituximab for the Treatment of Refractory Adult and Juvenile Dermatomyositis (DM) and Adult Polymyositis (PM) (NCT NCT00106184)

Last Updated: 2015-03-04

Results Overview

The Definition of Improvement for both adult and pediatric patients will be: 3 of any of the 6 core set measures improved by ≥ 20%, with no more than 2 of the core set measures worsening by ≥25% (worsening measure cannot include the MMT) at two consecutive visits. Of note, the MMT could not be one of the worsening measures. Core Set Measures Included: 1. Manual Muscle Testing (MMT)- Muscle Strength 2. Physician Global Disease Activity VAS Score 3. Health Assessment Questionnaire Index Score - Physical Function 4. Patient Global Assessment of Disease Activity VAS score 5. Extramuscular Activity - Myositis Disease Activity Assessment Tool 6. 2 or more elevated muscle enzymes (Aldolase, CK, AST, ALT, and LDH)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

200 participants

Primary outcome timeframe

Week 44 of treatment phase

Results posted on

2015-03-04

Participant Flow

Subject were screened and enrolled at 26 US and 4 international sites.

In an effort to exclude IBM (Inclusion Body Myositis) and other myositis mimics, the medical records and muscle biopsy results (if available) of adults with PM were reviewed by a 3-member Adjudication Committee before enrollment.

Participant milestones

Participant milestones
Measure	Treatment Group A (Rituximab Wks 0 and 1) Subjects received rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A) Rituximab : Treatment Group A - intravenous rituximab 750mg/m2 BSA (Body Surface Area) up to a maximum dose of 1 gram at Weeks 0 and 1 Placebo : Treatment Group A: placebo infusion at Weeks 8 and 9	Treatment Group B (Rituximab Wks 8 and 9) Subjects received placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B) Group B - intravenous rituximab 750mg/m2 BSA up to a maximum does of 1 gram at Weeks 8 and 9 Treatment Group B: placebo infusion at Weeks 0 and 1
Overall Study STARTED	96	104
Overall Study Treated	93	102
Overall Study COMPLETED	93	102
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Group A (Rituximab Wks 0 and 1) Subjects received rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A) Rituximab : Treatment Group A - intravenous rituximab 750mg/m2 BSA (Body Surface Area) up to a maximum dose of 1 gram at Weeks 0 and 1 Placebo : Treatment Group A: placebo infusion at Weeks 8 and 9	Treatment Group B (Rituximab Wks 8 and 9) Subjects received placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B) Group B - intravenous rituximab 750mg/m2 BSA up to a maximum does of 1 gram at Weeks 8 and 9 Treatment Group B: placebo infusion at Weeks 0 and 1
Overall Study Withdrawal by Subject	3	2

Baseline Characteristics

Rituximab for the Treatment of Refractory Adult and Juvenile Dermatomyositis (DM) and Adult Polymyositis (PM)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A n=96 Participants Subjects received rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A) Rituximab : Treatment Group A - intravenous rituximab 750mg/m2 BSA up to a maximum dose of 1 gram at Weeks 0 and 1 Placebo : Treatment Group A: placebo infusion at Weeks 8 and 9	Group B n=104 Participants Subjects received placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B) Group B - intravenous rituximab 750mg/m2 BSA up to a maximum does of 1 gram at Weeks 8 and 9 Treatment Group B: placebo infusion at Weeks 0 and 1	Total n=200 Participants Total of all reporting groups
Age, Categorical <=18 years	17 Participants n=5 Participants	19 Participants n=7 Participants	36 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	70 Participants n=5 Participants	80 Participants n=7 Participants	150 Participants n=5 Participants
Age, Categorical >=65 years	9 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants
Age, Continuous	43.1 years STANDARD_DEVIATION 18.23 • n=5 Participants	40.7 years STANDARD_DEVIATION 18.4 • n=7 Participants	41.8 years STANDARD_DEVIATION 18.3 • n=5 Participants
Sex: Female, Male Female	68 Participants n=5 Participants	78 Participants n=7 Participants	146 Participants n=5 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	26 Participants n=7 Participants	54 Participants n=5 Participants
Region of Enrollment United States	87 participants n=5 Participants	98 participants n=7 Participants	185 participants n=5 Participants
Region of Enrollment Czech Republic	4 participants n=5 Participants	3 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment Canada	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Sweden	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 44 of treatment phase

Population: Intention to Treat (ITT)

Outcome measures

Outcome measures
Measure	Group A (Rituximab Wks 0 and 1) n=96 Participants Subjects received rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A) Rituximab : Treatment Group A - intravenous rituximab 750mg/m2 BSA up to a maximum dose of 1 gram at Weeks 0 and 1 Placebo : Treatment Group A: placebo infusion at Weeks 8 and 9	Group B (Rituximab Wks 8 and 9) n=104 Participants Group B - intravenous rituximab 750mg/m2 BSA up to a maximum does of 1 gram at Weeks 8 and 9 Treatment Group B: placebo infusion at Weeks 0 and 1
Comparison Between the Time to Improvement Between the Two Groups of IIM (Idiopathic Inflammatory Myopathy) Patients	20.2 Weeks Interval 8.0 to 44.0	20.0 Weeks Interval 8.0 to 44.0

SECONDARY outcome

Timeframe: Week 8 of the treatment phase

Population: Intention to Treat (ITT)

Outcome measures

Outcome measures
Measure	Group A (Rituximab Wks 0 and 1) n=96 Participants Subjects received rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A) Rituximab : Treatment Group A - intravenous rituximab 750mg/m2 BSA up to a maximum dose of 1 gram at Weeks 0 and 1 Placebo : Treatment Group A: placebo infusion at Weeks 8 and 9	Group B (Rituximab Wks 8 and 9) n=104 Participants Group B - intravenous rituximab 750mg/m2 BSA up to a maximum does of 1 gram at Weeks 8 and 9 Treatment Group B: placebo infusion at Weeks 0 and 1
Response Rates (Proportion of Improved Patients) Between Groups A (Rituximab Wks 0 and 1) and B (Rituximab Wks 8 and 9) at Week 8	14 participants	21 participants

SECONDARY outcome

Timeframe: Week 44 of treatment phase

Population: Intention to Treat (ITT)

Number of participants with a 20% improvement in MMT over baseline on two consecutive time points.

Outcome measures

Outcome measures
Measure	Group A (Rituximab Wks 0 and 1) n=96 Participants Subjects received rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A) Rituximab : Treatment Group A - intravenous rituximab 750mg/m2 BSA up to a maximum dose of 1 gram at Weeks 0 and 1 Placebo : Treatment Group A: placebo infusion at Weeks 8 and 9	Group B (Rituximab Wks 8 and 9) n=104 Participants Group B - intravenous rituximab 750mg/m2 BSA up to a maximum does of 1 gram at Weeks 8 and 9 Treatment Group B: placebo infusion at Weeks 0 and 1
20% Improvement in Manual Muscle Testing (MMT) Over Baseline on Two Consecutive Time Points (Muscle is the Primary Organ of Involvement, and MMT is the One Objective Measurement of the Definition of Improvement [DOI])	14 Participants	21 Participants

Adverse Events

Treatment Group A

Serious events: 24 serious events

Other events: 45 other events

Deaths: 0 deaths

Treatment Group B

Serious events: 41 serious events

Other events: 55 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Treatment Group A n=96 participants at risk Subjects received rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A) Rituximab : Treatment Group A - intravenous rituximab 750mg/m2 BSA up to a maximum dose of 1 gram at Weeks 0 and 1 Placebo : Treatment Group A: placebo infusion at Weeks 8 and 9	Treatment Group B n=104 participants at risk Subjects received placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B) Group B - intravenous rituximab 750mg/m2 BSA up to a maximum does of 1 gram at Weeks 8 and 9 Treatment Group B: placebo infusion at Weeks 0 and 1
General disorders Headache	13.5% 13/96 • Number of events 13 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	11.5% 12/104 • Number of events 12 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Gastrointestinal disorders Nausea	10.4% 10/96 • Number of events 10 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	9.6% 10/104 • Number of events 10 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Infections and infestations Bronchitis	6.2% 6/96 • Number of events 6 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	3.8% 4/104 • Number of events 4 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Gastrointestinal disorders Diarrhea	6.2% 6/96 • Number of events 6 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	8.7% 9/104 • Number of events 9 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
General disorders Fever	6.2% 6/96 • Number of events 6 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	9.6% 10/104 • Number of events 10 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Respiratory, thoracic and mediastinal disorders Cough	4.2% 4/96 • Number of events 4 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	9.6% 10/104 • Number of events 10 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.

Additional Information

Chester V. Oddis, MD

University of Pittsburgh

Phone: 412-383-8861

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Treatment Group A n=96 participants at risk Subjects received rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A) Rituximab : Treatment Group A - intravenous rituximab 750mg/m2 BSA up to a maximum dose of 1 gram at Weeks 0 and 1 Placebo : Treatment Group A: placebo infusion at Weeks 8 and 9	Treatment Group B n=104 participants at risk Subjects received placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B) Group B - intravenous rituximab 750mg/m2 BSA up to a maximum does of 1 gram at Weeks 8 and 9 Treatment Group B: placebo infusion at Weeks 0 and 1
Infections and infestations Clostridium Infection	0.00% 0/96 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.96% 1/104 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Blood and lymphatic system disorders Anemia	1.0% 1/96 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.00% 0/104 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Cardiac disorders Cardiac Ischemia/myocardial infarction	1.0% 1/96 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	1.9% 2/104 • Number of events 2 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Cardiac disorders Congestive Heart Failure	1.0% 1/96 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.96% 1/104 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Cardiac disorders Myocarditis	0.00% 0/96 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.96% 1/104 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Gastrointestinal disorders Abdominal Pain	1.0% 1/96 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.00% 0/104 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Cardiac disorders Ventricular Arrhythmia	1.0% 1/96 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.00% 0/104 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Gastrointestinal disorders Constipation	1.0% 1/96 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.00% 0/104 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Gastrointestinal disorders Dysphagia	0.00% 0/96 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.96% 1/104 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Gastrointestinal disorders Gastritis	1.0% 1/96 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	2.9% 3/104 • Number of events 3 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Hepatobiliary disorders Cholecystitis	0.00% 0/96 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	1.9% 2/104 • Number of events 2 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Infections and infestations Cellulitis	2.1% 2/96 • Number of events 2 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	1.9% 2/104 • Number of events 2 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Infections and infestations Herpes Zoster	0.00% 0/96 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	1.9% 2/104 • Number of events 2 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Infections and infestations Histoplasmosis	0.00% 0/96 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.96% 1/104 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Infections and infestations Pneumonia	3.1% 3/96 • Number of events 3 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	3.8% 4/104 • Number of events 4 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Vascular disorders Raynaud Ulcer	1.0% 1/96 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.96% 1/104 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Infections and infestations Viral Infection	0.00% 0/96 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.96% 1/104 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Infections and infestations Urinary Tract Infection	1.0% 1/96 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.00% 0/104 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Musculoskeletal and connective tissue disorders Muscle Weakness - Disease Flare	2.1% 2/96 • Number of events 2 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.96% 1/104 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Musculoskeletal and connective tissue disorders Fracture	0.00% 0/96 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	1.9% 2/104 • Number of events 2 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Musculoskeletal and connective tissue disorders Pain	1.0% 1/96 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.00% 0/104 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Infections and infestations Joint Infection	1.0% 1/96 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.00% 0/104 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignancy	0.00% 0/96 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	2.9% 3/104 • Number of events 3 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Nervous system disorders Neurological Disorder - Aseptic Meningitis	0.00% 0/96 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.96% 1/104 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Nervous system disorders Syncope	0.00% 0/96 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.96% 1/104 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Psychiatric disorders Anxiety	1.0% 1/96 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.00% 0/104 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Psychiatric disorders Depression	0.00% 0/96 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.96% 1/104 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Renal and urinary disorders Kidney Stones	1.0% 1/96 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.00% 0/104 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	1.0% 1/96 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.00% 0/104 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	1.0% 1/96 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.00% 0/104 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Skin and subcutaneous tissue disorders Rash	0.00% 0/96 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.96% 1/104 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Surgical and medical procedures Surgical Procedure	1.0% 1/96 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	6.7% 7/104 • Number of events 7 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Vascular disorders Thrombosis	0.00% 0/96 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.96% 1/104 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Vascular disorders Death - Cerebral Vascular Accident	1.0% 1/96 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.	0.00% 0/104 • Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.