Clinical Trial: Safety and Effectiveness of h5G1.1-mAb for Dermatomyositis

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

Official Title: A Randomized, Third-Party-Blind, Placebo-Controlled Pilot Study of the Effect of h5G1.1-mAb on Dermatomyositis Patients

Brief Summary:

This study will evaluate the safety and effectiveness of the experimental drug h5G1.1-mAb in treating patients with dermatomyositis. This disease, which causes skin rash, muscle weakness, and sometimes various other symptoms, may be due to an immune system abnormality. Drugs currently used to treat dermatomyositis, such as prednisone and various anticancer drugs, often have serious side effects and may not work in all patients. h5G1.1-mAb is a genetically engineered antibody that blocks the activity of certain proteins involved in the immune reaction that produces inflammation.

Patients age 18 years and older who have had dermatomyositis for at least 6 months and who have not improved with prednisone or other therapies, or who cannot tolerate prednisone or other therapies, may be eligible for this 12-week study. Candidates will have a history and physical examination, including blood and urine tests, throat culture, and muscle strength testing. Participants will be randomly assigned to receive either h5G1.1-mAb or placebo (an inactive substance). The drug or placebo will be given intravenously (through a thin tube inserted into a vein) once a week for five doses and then every other week for two more doses.

Participants will undergo the following additional tests at various intervals during the study as follows:

  1. Complete physical examination ( visit 9)
  2. Blood and urine tests (various intervals)
  3. Muscle strength testing, assessment of ability to perform daily tasks, and completion of questionnaire regarding functional abilities (visits 2, 6 and 9)
  4. Ultrasound imaging of muscle (during certain muscle exercises) (visits 2, 6 and 9)

  5. Detailed Summary:

    This is a randomized, third-party, placebo-controlled pilot study of h5G1.1-mAb, an antibody directed at the complement component C5, administered to patients with dermatomyositis with persistent disease. We are one of the four groups taking part in a multicenter trial under the sponsorship of Alexion Pharmaceuticals, Inc.

    In dermatomytosis, humorally-mediated damage to muscle and skin microvasculature appears very important. The deposition of the membrane attack complex (C5-9) on the capillaries has been shown to precede the destruction of muscle fibers and to be a specific finding in the skin lesion. These observations, along with the recent discovery of the effectiveness of intravenous gammaglobulin (IVIG) in dermatomyositis, support the role of complement activation in the pathogenesis of dermatomyositis. Among the activated components of the complement system, the products that are generated after cleavage of C5, namely, C5a and C5b-9, are potent inflammatory mediators with pleiotropic activities. Inhibition of complement activation at C5 would prevent the formation of these pro-inflammatory molecules while allowing the generation of C3b, which is critical for opsonization and immune complex clearance. C5 inhibition therefore represents a potentially effective therapeutic modality for dermatomyositis.

    Anti-C5 monoclonal antibodies are designed to prevent the cleavage of C5. A murine monoclonal antibody to human C5, m5G1.1-mAb, was humanized (h5G1.1-mAb) by grafting the antibody's antigen-binding CDR regions onto human antibody-derived framework and constant domains. This antibody is being made available by Alexion Pharmaceuticals, and will be used under their IND.

    There will be 15 patients entered (with the goal of 12 evaluable patients) distributed among two treatment
    Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

    Current Primary Outcome:

    Original Primary Outcome:

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    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: April 25, 2000
    Date Started: April 2000
    Date Completion: December 2001
    Last Updated: March 3, 2008
    Last Verified: December 2001