Alemtuzumab to Treat Sporadic Inclusion Body Myositis
This study will examine the safety and effectiveness of alemtuzumab (Campath® (Registered Trademark)) for improving muscle strength in patients with sporadic inclusion body myositis (s-IBM). The most common inflammatory muscle disease in people over the age of 50, s-IBM progresses steadily, leading to severe weakness and wasting of the muscles in the arms and legs. The cause of s-IBM is not known, but it may be an autoimmune disease, in which the body's immune cells (white blood cells) attack and destroy parts of muscle. Alemtuzumab is a laboratory-made antibody currently approved to treat certain leukemias. It has also been used to treat patients with autoimmune conditions such as rheumatoid arthritis, vasculitis, multiple sclerosis, and tissue rejection associated with transplantation. Alemtuzumab destroys white blood cells that have a protein called CD52 on their surface and that might be among the cells attacking muscle.
Patients with s-IBM are eligible for this study. Candidates are screened with physical and neurological examinations, blood tests, and an electrocardiogram. Participants undergo the following tests and procedures:
- Campath administration: Patients are admitted to the NIH Clinical Center for 1 to 1-1/2 weeks for intravenous infusions of Campath, given every other day for a total of 4 infusions.
- Follow-up visits after infusions: Patients are monitored for up to 1 year with periodic blood tests, physical and neurological examinations, medical history, muscle strength measurements, and a review of symptoms, including the ability to perform daily living activities.
- Lymphapheresis: Patients undergo this procedure for collecting large numbers of white blood cells twice - once at the beginning of the study and again after 6 months. Blood is removed through a needle in an arm vein and flows through a machine that separates it into its components by centrifugation (spinning). The white cells and plasma are removed and the red cells and platelets are returned to the patients through the same needle or through another needle in the other arm.
- Muscle biopsy: Muscle biopsies are done in the operating room under local anesthetic. A small incision is made in the thigh or upper arm and a small piece of muscle is removed. Biopsies are done at the beginning of the study and again after 6 months.
|Study Design:||Primary Purpose: Treatment|
|Official Title:||Effects of a T Cell-Depleting Monoclonal Antibody, Alemtuzumab, in Patients With Inclusion Body Myositis: A Pilot Clinicopathological Study|
- Change in the muscle strength at 6 months by 15%.
|Study Start Date:||March 2004|
|Study Completion Date:||March 2007|
|Primary Completion Date:||March 2007 (Final data collection date for primary outcome measure)|
Drug: Alemtuzumab (Campath)
Sporadic Inclusion-Body Myositis (s-IBM) is the most common muscle disease in patients above the age of 50 years. It is an inflammatory myopathy mediated by sensitized, cytotoxic CD8+ T cells that clonally expand in situ and invade MHC-I-expressing muscle fibers. The antigen recognized by the T cells is unknown. The disease is progressive, resists the currently available immunotherapies and leads to wheelchair confinement. Applying therapeutic strategies with agents that deplete T cells clones and investigating the antigenic specificity of the endomysial T cells is expected to enhance our understanding of the cause of s-IBM and lead to clinical improvement. The present study is designed to: a) test in a pilot study the safety, T cell depletion of the endomysial T cells and clinical efficacy of the monoclonal antibody Alemtuzumab in 20 patients with s-IBM followed for 12 months by serial quantitative assessment of muscle strength; b) explore the spectrum of the antigens recognized by the T cells extracted from the muscle biopsy specimens by searching for immune dominant peptides using positional scanning synthetic combinational peptide libraries, before and after therapy; and c) determine the reciprocal relationship between clinical response and endomysial inflammatory mediators before and after treatment. It is anticipated that the study may lead to identification of putative antigens that trigger the disease, clarify the significance of the inflammation and amyloid deposits in muscle fiber injury and provide a novel therapy for s-IBM patients.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|