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Trial record 2 of 85 for:    Polymyositis AND Myopathy

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

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ClinicalTrials.gov Identifier: NCT00106184
Recruitment Status : Completed
First Posted : March 22, 2005
Results First Posted : March 4, 2015
Last Update Posted : March 4, 2015
Sponsor:
Collaborators:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Genentech, Inc.
Biogen
Information provided by (Responsible Party):
Chester Oddis, University of Pittsburgh

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Myositis
Dermatomyositis
Polymyositis
Juvenile Dermatomyositis
Interventions Drug: Rituximab
Drug: Placebo
Enrollment 200
Recruitment Details Subject were screened and enrolled at 26 US and 4 international sites.
Pre-assignment Details 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.
Arm/Group Title Treatment Group A (Rituximab Wks 0 and 1) Treatment Group B (Rituximab Wks 8 and 9)
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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

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

Period Title: Overall Study
Started 96 104
Treated 93 [1] 102 [2]
Completed 93 102
Not Completed 3 2
Reason Not Completed
Withdrawal by Subject             3             2
[1]
96 subjects were randomized.
[2]
104 subjects were randomized.
Arm/Group Title Group A Group B Total
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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

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 of all reporting groups
Overall Number of Baseline Participants 96 104 200
Hide Baseline Analysis Population Description
3 subjects in Group A and 2 subjects in Group B were excluded from analysis due to withdrawing from the study. These subjects either did not receive a full dose of study drug at week 0 or no study drug at all.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 96 participants 104 participants 200 participants
<=18 years
17
  17.7%
19
  18.3%
36
  18.0%
Between 18 and 65 years
70
  72.9%
80
  76.9%
150
  75.0%
>=65 years
9
   9.4%
5
   4.8%
14
   7.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 96 participants 104 participants 200 participants
43.1  (18.23) 40.7  (18.4) 41.8  (18.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 96 participants 104 participants 200 participants
Female
68
  70.8%
78
  75.0%
146
  73.0%
Male
28
  29.2%
26
  25.0%
54
  27.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 96 participants 104 participants 200 participants
United States 87 98 185
Czech Republic 4 3 7
Canada 2 3 5
Sweden 3 0 3
1.Primary Outcome
Title Comparison Between the Time to Improvement Between the Two Groups of IIM (Idiopathic Inflammatory Myopathy) Patients
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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)
Time Frame Week 44 of treatment phase
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Hide Analysis Population Description
Intention to Treat (ITT)
Arm/Group Title Group A (Rituximab Wks 0 and 1) Group B (Rituximab Wks 8 and 9)
Hide Arm/Group Description:

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 - 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 Number of Participants Analyzed 96 104
Median (Full Range)
Unit of Measure: Weeks
20.2
(8 to 44)
20.0
(8 to 44)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group A (Rituximab Wks 0 and 1), Group B (Rituximab Wks 8 and 9)
Comments Proportional hazards model
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.74
Comments [Not Specified]
Method Log Rank
Comments No confidence intervals as no parameters were estimated.
2.Secondary Outcome
Title Response Rates (Proportion of Improved Patients) Between Groups A (Rituximab Wks 0 and 1) and B (Rituximab Wks 8 and 9) at Week 8
Hide Description

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)
Time Frame Week 8 of the treatment phase
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat (ITT)
Arm/Group Title Treatment Group A (Rituximab Wks 0 and 1) Treatment Group B (Rituximab Wks 8 and 9)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 96 104
Measure Type: Number
Unit of Measure: participants
14 21
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Group A (Rituximab Wks 0 and 1), Treatment Group B (Rituximab Wks 8 and 9)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.90
Comments [Not Specified]
Method Chi-squared
Comments Difference in baseline muscle enzymes therefore tested the difference in the proportions adjusting for the baseline values.
3.Secondary Outcome
Title 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])
Hide Description Number of participants with a 20% improvement in MMT over baseline on two consecutive time points.
Time Frame Week 44 of treatment phase
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat (ITT)
Arm/Group Title Treatment Group A (Rituximab Wks 0 and 1) Treatment Group B (Rituximab Wks 8 and 9)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 96 104
Measure Type: Number
Unit of Measure: Participants
14 21
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Group A (Rituximab Wks 0 and 1), Treatment Group B (Rituximab Wks 8 and 9)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.90
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Time Frame Reported Adverse Events (AEs) include events starting on or after Week 0 and on or before Week 44 of the study.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment Group A Treatment Group B
Hide Arm/Group Description

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

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

All-Cause Mortality
Treatment Group A Treatment Group B
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment Group A Treatment Group B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   24/96 (25.00%)      41/104 (39.42%)    
Blood and lymphatic system disorders     
Anemia * 1 [1]  1/96 (1.04%)  1 0/104 (0.00%)  0
Cardiac disorders     
Cardiac Ischemia/myocardial infarction * 1  1/96 (1.04%)  1 2/104 (1.92%)  2
Congestive Heart Failure * 1  1/96 (1.04%)  1 1/104 (0.96%)  1
Myocarditis * 1  0/96 (0.00%)  0 1/104 (0.96%)  1
Ventricular Arrhythmia * 1  1/96 (1.04%)  1 0/104 (0.00%)  0
Gastrointestinal disorders     
Abdominal Pain * 1  1/96 (1.04%)  1 0/104 (0.00%)  0
Constipation * 1  1/96 (1.04%)  1 0/104 (0.00%)  0
Dysphagia * 1  0/96 (0.00%)  0 1/104 (0.96%)  1
Gastritis * 1  1/96 (1.04%)  1 3/104 (2.88%)  3
Hepatobiliary disorders     
Cholecystitis * 1  0/96 (0.00%)  0 2/104 (1.92%)  2
Infections and infestations     
Cellulitis * 1  2/96 (2.08%)  2 2/104 (1.92%)  2
Clostridium Infection * 1  0/96 (0.00%)  0 1/104 (0.96%)  1
Herpes Zoster * 1  0/96 (0.00%)  0 2/104 (1.92%)  2
Histoplasmosis * 1  0/96 (0.00%)  0 1/104 (0.96%)  1
Pneumonia * 1  3/96 (3.13%)  3 4/104 (3.85%)  4
Viral Infection * 1  0/96 (0.00%)  0 1/104 (0.96%)  1
Urinary Tract Infection * 1  0/96 (0.00%)  0 1/104 (0.96%)  1
Joint Infection * 1  1/96 (1.04%)  1 0/104 (0.00%)  0
Urinary Tract Infection * 1  1/96 (1.04%)  1 0/104 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Muscle Weakness - Disease Flare * 1  2/96 (2.08%)  2 1/104 (0.96%)  1
Fracture * 1  0/96 (0.00%)  0 2/104 (1.92%)  2
Pain * 1  1/96 (1.04%)  1 0/104 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignancy * 1  0/96 (0.00%)  0 3/104 (2.88%)  3
Nervous system disorders     
Neurological Disorder - Aseptic Meningitis * 1  0/96 (0.00%)  0 1/104 (0.96%)  1
Syncope * 1  0/96 (0.00%)  0 1/104 (0.96%)  1
Psychiatric disorders     
Anxiety * 1  1/96 (1.04%)  1 0/104 (0.00%)  0
Depression * 1  0/96 (0.00%)  0 1/104 (0.96%)  1
Renal and urinary disorders     
Kidney Stones * 1  1/96 (1.04%)  1 0/104 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pulmonary Embolism * 1  1/96 (1.04%)  1 0/104 (0.00%)  0
Respiratory Failure * 1  1/96 (1.04%)  1 0/104 (0.00%)  0
Skin and subcutaneous tissue disorders     
Rash * 1  0/96 (0.00%)  0 1/104 (0.96%)  1
Surgical and medical procedures     
Surgical Procedure * 1  1/96 (1.04%)  1 7/104 (6.73%)  7
Vascular disorders     
Raynaud Ulcer * 1  1/96 (1.04%)  1 1/104 (0.96%)  1
Thrombosis * 1  0/96 (0.00%)  0 1/104 (0.96%)  1
Death - Cerebral Vascular Accident * 1  1/96 (1.04%)  1 0/104 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 10.0
[1]
Anemia die to esophageal ulcers
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment Group A Treatment Group B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   45/96 (46.88%)      55/104 (52.88%)    
Gastrointestinal disorders     
Nausea * 1  10/96 (10.42%)  10 10/104 (9.62%)  10
Diarrhea * 1  6/96 (6.25%)  6 9/104 (8.65%)  9
General disorders     
Headache * 1  13/96 (13.54%)  13 12/104 (11.54%)  12
Fever * 1  6/96 (6.25%)  6 10/104 (9.62%)  10
Infections and infestations     
Bronchitis * 1  6/96 (6.25%)  6 4/104 (3.85%)  4
Respiratory, thoracic and mediastinal disorders     
Cough * 1  4/96 (4.17%)  4 10/104 (9.62%)  10
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 10.0
There was an overestimate of the rapidity of the rituximab response and an underestimate of DOI in those receiving placebo.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Chester V. Oddis, MD
Organization: University of Pittsburgh
Phone: 412-383-8861
EMail: cvo5@pitt.edu
Responsible Party: Chester Oddis, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00106184     History of Changes
Obsolete Identifiers: NCT00393237
Other Study ID Numbers: N01 AR042273
5R01AR061298-02 ( U.S. NIH Grant/Contract )
HHSN26420042273C
First Submitted: March 21, 2005
First Posted: March 22, 2005
Results First Submitted: October 10, 2013
Results First Posted: March 4, 2015
Last Update Posted: March 4, 2015