Trial Information

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

Rituximab is a chimeric, murine-human, genetically engineered monoclonal antibody directed
against the CD20 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 and 1 after receiving study medication, to determine the
effects of rituximab on muscle tissue.

If a participant is unable to locate a near-by clinical center, the adult and pediatric
centers at the National Institute of Health located in Bethesda, Maryland have funds
available to assist with travel costs.

NIH SUB-STUDY: "Rituximab to Treat Dermatomyositis and Polymyositis"

- This study is currently recruiting patients.

- Sponsored by: National Institute of Environmental Health Sciences (NIEHS)

- Information provided by: National Institutes of Health Clinical Center (CC)

- Expected Total Enrollment: 30

- Study start: October 2006

- Location and Contact Information: Patient Recruitment and Public Liaison Office;(800)
411-1222; prpl@mail.cc.nih.gov; TTY: 1-866-411-1010

The NIH sub-study will take advantage of the multi-center core RIM trial to identify changes
in gene expression patterns in muscle, skin, and peripheral blood and the imaging features
and immunopathology of muscle, skin, and peripheral cells before (week 0) and after (week
16) therapy. These changes will also be correlated with the large number of clinical,
laboratory, and research variables already planned to be collected in the core RIM Study.
Furthermore, knowing specifically which gene expression patterns are altered in resistant
patients before rituximab, and which are changed after rituximab therapy - in conjunction
with flow cytometry of peripheral cells and immunopathology of the tissues - will help in
understanding more about the pathogenesis of myositis and the possible contribution of B
lymphocytes and their subsets.

Patients with dermatomyositis and polymyositis who meet the inclusion/exclusion criteria for
the core RIM trial may be eligible for this sub-study. The following procedures will be
conducted in addition to the core RIM trial procedures during the 13 clinic visits over a
period of 44 weeks:

- Weeks 0, 16: Muscle and skin biopsy (adult only). Small samples of muscle and skin
tissue will be surgically removed for examination under a microscope.

- Weeks 0, 8, 16, 44: Skin evaluation and photography. The effect of the disease on the
skin will be thoroughly evaluated and photographs of any rashes and of the skin around
the nails will be taken.

- Weeks 0, 8, 16, 44: Magnetic resonance imaging (MRI). All participants will have MRI
scans of the skin and of the muscle in the legs. Adults will also have an MRI to
examine blood flow in the muscle.