A Pilot Study of Etanercept in Dermatomyositis

• Status: Completed
• Trial end date: 2010-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of the study is to obtain preliminary data regarding the safety and tolerability of etanercept in DM. In addition, we will use the study to assess the variability, reliability, and responsiveness of the core set of outcome measures recommended by IMACS. The study will be performed under the aegis of the Muscle Study Group (MSG), consisting of experienced investigators with an avid interest in myopathies. The ultimate goal of this pilot study will be to obtain necessary, prerequisite information important in designing future therapeutic trials of etanercept and other agents in patients with DM. The specific aims of the study are:

Aim 1: To preliminarily assess the safety and tolerability of etanercept in patients with DM.

Aim 2: To assess the safety and tolerability of prednisone in the dosing schedule we propose to use.

Aim 3: To evaluate outcome measures recommended by IMACS and assess their variability, reliability, and responsiveness in order to facilitate the design of future therapeutic trials in the inflammatory myopathies.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Brigham and Women's Hospital
• Collaborator: Amgen
• Treatments: Etanercept

Criteria

Inclusion Criteria:

Study subjects must meet the following criteria:

1. Meet the diagnostic criteria for DM (a-c; a,b,d; or a,c,d)

1. Subjects must have symmetric proximal greater than distal weakness

2. Characteristic DM rash consisting of any or all of the following: heliotrope, shawl sign, V-sign, Gottron's sign, Gottron's papules, periungual telangiectasias

3. Laboratory evidence of myopathy with at least one of the following: an elevated serum CK or aldolase level, myositis-specific antibody, electromyography (EMG) demonstrating myopathic features (e.g., muscle membrane instability, myopathic units, or early recruitment), or an abnormal skeletal muscle MRI showing diffuse or patchy edema within the muscles.

4. A muscle biopsy will be optional if the patient fulfills criteria a-c. The subject must demonstrate symmetric proximal weakness (criteria a) for entry into the study. If the subject does not have a definite rash (criteria b) or laboratory evidence of a myopathy (criteria c), a muscle biopsy will be required. The muscle biopsy must demonstrate one of the following: perifascicular atrophy, expression of MHC 1 on perifascicular muscle fibers, MAC deposition on small blood vessels, tubuloreticular inclusions in endothelial cells on EM, or MXA expression on muscle fibers of blood vessels

2. Newly diagnosed subjects should be able to walk independently 30 feet (cane, walkers, orthoses allowed). However, subjects with refractory dermatomyositis may be non-ambulatory.

3. Age > 18 years

4. Patients must not use topical skin ointments for treatment of the dermatological manifestations as it will interfere with skin assessment.

5. Men and women of childbearing age must be willing to use a method of birth control.

6. Able to give informed consent

7. Subject or designee must have the ability to self-inject investigational product or have a care giver at home who can administer subcutaneous injections

Exclusion Criteria

The presence of any of the following excludes subject participation in the study:

1. Presence of any one of the following medical conditions: active infection, uncontrolled diabetes mellitus, MI, CVA or TIA within 3 months of screening visit, symptomatic cardiomyopathy (congestive heart failure), symptomatic coronary artery disease, uncontrolled hypertension (sitting systolic BP <80 mm Hg or > 160 or diastolic BP > 100 mm Hg), oxygen-dependent severe pulmonary disease, systemic lupus erythematosus (SLE), cancer (other than basal cell skin cancer) less than 5 years previously, HIV or other immunosuppressing disease, positive PPD test or any history of mycobacterial disease, chronic hepatitis B or hepatitis C, history of multiple sclerosis, transverse myelitis, optic neuritis, chronic inflammatory demyelinating neuropathy, epilepsy, or other chronic serious medical illnesses

2. Presence of any of the following on routine blood screening: WBC<3000, Platelets < 100,000, hematocrit < 30%, BUN > 30 mg %, symptomatic liver disease with serum albumin < 3 G/DL, PT or PTT > upper range of control values

3. Forced Vital Capacity < 50% of predicted

4. History of non-compliance with other therapies

5. Any prior or concurrent cyclophosphamide, or current use of any immunosuppressive agent besides methotrexate (e.g., azathioprine, mycophenolate, or cyclosporine)

6. Coexistence of other neuromuscular disease that may complicate interpretation of the results of the study

7. Drug or alcohol abuse within last 3 months

8. Pregnancy or breast feeding

9. Juvenile DM

10. Subjects who have known hypersensitivity to Enbrel or any of its components or who is known to have antibodies to etanercept

11. Use of a live vaccine 90 days prior to, or during this study.

12. Subject is currently enrolled in another investigational device or drug trial(s), or subject has received other investigational agent(s) within 28 days of baseline visit.

13. Concurrent sulfasalazine therapy