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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Rituximab Therapy in Refractory Adult and Juvenile Idiopathic Inflammatory Myopathy (IIM)

Brief Summary:

Rituximab is a man-made antibody used to treat certain types of cancer. This study will determine whether rituximab is an effective treatment for adult and pediatric patients with dermatomyositis or polymyositis.

Study hypotheses: 1) The time to improvement in Group A patients (receiving rituximab first) will occur significantly earlier than in Group B patients (receiving rituximab later). 2) The proportion of patients improved at Week 8 of the treatment phase will be significantly greater in Group A than in Group B.


Detailed Summary:

Rituximab is a chimeric, murine-human, genetically engineered monoclonal antibody directed against the CD20 (cluster of differentiation antigen 20) antigen found on the surface of B-lymphocytes and is known to deplete B cells when administered intravenously. It is approved to treat non-Hodgkin's lymphoma. Rituximab has been used for autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and immune-mediated hematologic disorders. It has also been studied and used in small numbers of patients with myositis. This study will evaluate the efficacy of rituximab in treating refractory adult and pediatric patients with dermatomyositis and adult polymyositis.

A patient's participation in this study will last approximately 45 weeks. At screening, participants will have a physical exam, muscle strength assessment, an electrocardiogram, and blood and urine collection; they will also be asked to complete several questionnaires. All participants will receive 2 infusions of rituximab and 2 infusions of placebo. Participants will be randomly assigned to one of two groups. Group A will receive rituximab at Weeks 0 and 1 and placebo at Weeks 8 and 9. Group B will receive placebo at Weeks 0 and 1 and rituximab at Weeks 8 and 9. Each infusion will be given on an outpatient basis over a minimum of approximately 5 hours' time.

There will be a total of 14 study visits. All participants will visit the outpatient clinic at selected time points for muscle strength testing, a physical exam, disease activity measurements, and blood collection. During the study, participants will be monitored closely for improvement or worsening of their disease and for serious drug related side effects. Some participants will be asked if they are willing to undergo 2 muscle biopsy procedures, 1 prior to receiving study medication a
Sponsor: University of Pittsburgh

Current Primary Outcome: Comparison Between the Time to Improvement Between the Two Groups of IIM (Idiopathic Inflammatory Myopathy) Patients [ Time Frame: Week 44 of treatment phase ]

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)


Original Primary Outcome: Comparison of time to achieve the definition of improvement between the two groups of rituximab-treated patients

Current Secondary Outcome:

  • Response Rates (Proportion of Improved Patients) Between Groups A (Rituximab Wks 0 and 1) and B (Rituximab Wks 8 and 9) at Week 8 [ Time Frame: Week 8 of the treatment phase ]

    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)
  • 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]) [ Time Frame: Week 44 of treatment phase ]
    Number of participants with a 20% improvement in MMT over baseline on two consecutive time points.


Original Secondary Outcome: Response rates (proportion of improved patients) between Groups A and B at Week 9 of the treatment phase

Information By: University of Pittsburgh

Dates:
Date Received: March 21, 2005
Date Started: March 2006
Date Completion:
Last Updated: March 3, 2015
Last Verified: March 2015