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A Pilot Study of Etanercept in Dermatomyositis

Phase 1
18 Years
65 Years
Not Enrolling

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Trial Information

A Pilot Study of Etanercept in Dermatomyositis

Dermatomyositis (DM) is one of the major subtypes of idiopathic inflammatory myopathy.
Prednisone is the initial treatment of choice in most patients with DM. However, because of
the high rate of patients with disabling weakness despite treatment with prednisone, the
long-term side effects of prednisone, and the many side effects associated with other
second-line immunosuppressive agents (e.g., methotrexate, azathioprine), better treatment
options are needed. There is evidence that tumor necrosis factor-a (TNF-a) plays a role in
the pathogenesis of DM. Thus, etanercept, which blocks TNF-a, is a logical drug to assess
in DM. Etanercept has been associated with a number of side effects including an increased
risk of infection, inducing other autoimmune diseases, and perhaps cancer. These risks may
be further enhanced in DM in which the frequency of other autoimmune disorders (e.g.,
connective tissue disease) and malignancy are already increased.

The goal of this pilot study will be to assess the safety and tolerability of etanercept in
DM.We will perform a double-blind, placebo-controlled pilot study of etanercept in 40
patients with DM randomized in a 3:1 ratio to receive etanercept or placebo. All newly
diagnosed and untreated patients will be started on a standard dose of prednisone and
tapering schedule. Refractory patients who have been or are currently being treated with
prednisone, IVIG, or methotrexate can also participate. Subjects will be followed for 1
year and we will assess various outcome variables recommended by the The International
Myositis Assessment Clinical Study Group (IMACS). The primary aim of the study is to
preliminarily assess the safety and tolerability of etanercept in patients with DM. We
hypothesize that etanercept will be safe and well tolerated in this population. The second
aim is to assess the safety and tolerability of prednisone in the dosing schedule we propose
to use. We hypothesize that most patients will be able to tolerate the reduction of the
prednisone dosage but most will not be able to be completely weaned off the medication. We
believe we will find a relationship between prednisone dosage and its related side effects.
The third aim of the study is to assess the variability, reliability, and responsiveness of
the outcome measures recommended by IMACS using this pilot study of etanercept as the
vehicle. The information gained from this study is necessary in order to design larger
therapeutic trials of etanercept and other drugs in dermatomyositis.

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

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

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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Occurrence of at Least One Adverse Event

Outcome Description:

Adverse events (AEs) were assessed using the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE). The grade of "mild", "moderate" or "severe" matches with the descriptions from the CTCAE dictionary. In general, a "Mild" AE is asymptomatic; clinical or diagnostic observations only; intervention not indicated. A "Moderate" AE is minimal, local or noninvasive intervention indicated; limiting activities of daily living. A "Severe" AE is medically significant but not immediately life-threatening; hospitalization or prolonged hospitalization indicated; disabling;

Outcome Time Frame:

at each visit during the 12 month study

Safety Issue:


Principal Investigator

Anthony A Amato, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Brigham and Women's Hospital


United States: Food and Drug Administration

Study ID:

1 R01 NS049639-01A2



Start Date:

March 2006

Completion Date:

June 2010

Related Keywords:

  • Dermatomyositis
  • dermatomyositis
  • etanercept
  • tumor necrosis factor alpha
  • Dermatomyositis



Brigham and Women's Hospital Boston, Massachusetts  02115