Alemtuzumab to Treat Sporadic Inclusion Body Myositis
Condition: Myositis, Inclusion Body
MeSH terms: Myositis; Myositis, Inclusion Body
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Alemtuzumab (Campath)
Intervention type(s): Drug
Intervention MeSH terms: Alemtuzumab
Primary purpose: Treatment
Keywords: Inflammation; Myositis; Humanized Monoclonal Antibody; Cytotoxic T Cells; Endomysial T Cells; Alemtuzumab; Monoclonal Antibodies; IBM; Anti-CD 52; Inclusion Body Myositis