Safety and Effectiveness of h5G1.1-mAb for Dermatomyositis

• Status: Completed
• Trial end date: 2001-12-01
• Target enrollment: 0
• Participant gender: All

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. Electrocardiogram (EKG) (visits 2 and 9)

6. Throat swab (culture) (visit 6)

7. Examination and photography of skin lesions (visits 2 and 9)

8. Skin biopsy - removal of small sample of skin tissue under local anesthetic (visits 2 and 9)

9. Magnetic resonance imaging (MRI) scan of muscles (visits 2 and 9)

10. Possible muscle biopsy - removal of small sample of muscle tissue under local anesthetic (visits 2 and 9).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Treatments: Eculizumab

Criteria

Patients age greater than or equal to 18 years.

Patients with a diagnosis of definite or probable dermatomyositis by criteria of Bohan et. al., with either active rash typical of dermatomyositis, history of rash typical of dermatomyositis, or Gottron's papules.

Patients with a manual muscle testing score less than or equal to 136/170.

Patients with a disease duration greater than or equal to 6 months.

Patients with persistent disease (defined as active rash plus CK greater than or equal to 2 times ULN), or rapidly progressive disease, or response to steroids with inability to taper dose, or unacceptable side effects of steroids.

Patients may be on stable (times 28 days prior to Visit 2) dose of MTX or AZA.

No other immunosuppressive agents times 84 days prior to first dose.

Patients on stable oral steroid use for 28 days prior to Visit 2.

Patients with adequate hematologic function, defined as hemoglobin greater than or equal to 8.5 g/dl, WBC greater than or equal to 3,000 mm(3), neutrophils greater than or equal to 1,200 mm(3), platelets greater than or equal to 100,000 mm(3).

Patients must be willing and able to give informed consent.

Women must be post-menopausal, surgically sterile or practicing a medically approved method of contraception.

Patients with liver disease will be excluded.

Patients with history of alcohol or drug abuse within two years of screening, or a history of positive Hepatitis B or Hepatitis C serology, unless vaccinated will be excluded.

Patients with renal insufficiency, defined as creatinine greater than or equal to 2.0 mg/dl will be excluded.

Patients with history of malignancy, except basal cell carcinoma and remote (greater than or equal to 5 years) malignancies in complete remission will be excluded.

Patients with history of poorly controlled diabetes will be excluded.

Patients with presence or suspicion of active infection, recent serious infection, or chronic/recurrent viral or bacterial infection will be excluded.

Patients with throat culture positive for pathogenic Neisseria species (meningitidis or gonorrhoeae) will be exluded. Subjects with a positive culture may be treated with appropriate antibiotic therapy and retested.

Patients with joint disease or replacement that would interfere with patient's ability to perform muscle testing will be excluded.

Patients with any clinically significant medical condition that is likely to interfere with the participation in the study or the evaluation of the study medication's safety profile will be excluded.

No patients with known or suspected hereditary complement deficiency will be excluded.

Patients with history of allergic reaction to murine proteins will be excluded.

Patients participating in any other investigational drug trial, or exposure to other investigational agent or device within thirty days prior to screening will be excluded.

Pregnant or breastfeeding patients will be excluded.

Women intending to conceive during the course of the study, including follow-up period will be excluded.

Patients with history of HIV, Lyme disease, or other environmentally induced myositis will be excluded.