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Phase 2
18 Years
Not Enrolling
Dermatomyositis, Polymyositis

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Trial Information

Tumor necrosis factor (TNF), a cytokine that has been implicated in the pathogenesis of many
diseases including inflammatory disorders, has been found to be elevated in the muscles of
patients with dermatomyositis (DM) and polymyositis (PM). A subset of patients with DM and
PM do not respond readily to conventional therapy. Therefore, a controlled trial using
infliximab, a chimeric IgG(1) kappa monoclonal antibody against TNF, may provide a
therapeutic option and advance understanding in the pathogenesis of these diseases. This
study is designed to determine the safety and efficacy of infliximab in patients with DM and
PM. We plan to enroll a maximum of 28 patients randomized at 1:1 ratio into 2 groups,
placebo vs. infliximab at 5 mg/kg body weight. In the first phase of the study the placebo
and infliximab infusions will be given at week 0, 2, 6 and 14. Primary outcome assessment
will be done at week 16. Those who respond according to the criteria set for improvement in
MMT will be given the option to remain on the same infusion (i.e. placebo or infliximab at 5
mg/kg body weight) at weeks 22, 30 and 38. Placebo non-responders will be given infliximab
at 5 mg/kg body weight in an open label fashion at weeks 16, 18, 22, 30 and 38. Patients
who were initially on 5 mg/kg body weight of infliximab who failed to respond based on the
criteria set will be placed on infliximab at 7.5 mg/kg body weight in an open label fashion
on weeks 22, 30 and 38. Pharmacokinetic modeling will be done in both phases of the study.
A muscle biopsy will be done before treatment and again at 16 weeks of treatment.
Microarray gene expression profiling of the muscle biopsy specimens will be done before
treatment and again at 16 weeks. Clinical, functional and serological evaluations will be
performed in every visit to assess other responses to treatment. Patients will be followed
for 30 weeks after study termination to evaluate the long-term effects of the drug.

Inclusion Criteria


Must be at least 18 years of age.

Diagnosis of probable or definite polymyositis or dermatomyositis as defined by Bohan and

i. Symmetrical proximal muscle weakness;

ii. Muscle biopsy abnormalities at some time during their disease:

1. Muscle fiber destruction;

2. Muscle fiber regeneration;

3. Perivascular and interstitial inflammatory infiltrates with muscle fiber destruction.

iii. Elevation of serum creatine phosphokinase (CPK), Transaminases, lactic
dehydrogenase (LDH) or aldolase activity;

iv. Electromyography changes:

1. Fibrillation potentials (on needle insertion at rest);

2. Complex repetitive discharges (on needle insertion at rest);

3. Positive sharp waves (on needle insertion at rest);

4. Short duration, low amplitude complex (polyphasic) potentials on contraction.

v. Typical skin rash. The classic skin manifestations include a purplish discoloration
of the eyelids (heliotrope rash) or papular, erythematous, scaly lesions over the knuckles
(Gottron's papules);

DEFINITE: any 4 of the criteria

PROBABLE: any 3 of the criteria

- Patients must have a baseline total muscle strength score of less than or equal to
120 but not less than 80 on manual muscle testing (MMT) or at least 25% decrease in
manual muscle strength.

- Ability to provide informed consent to all aspects of the study after full
information is provided.

- Evidence of active disease as measured by weakness, and an elevated CK, aldolase,
SGOT, SGPT, LDH or an active MRI. MR imaging may demonstrate signal abnormalities in
affected muscles secondary to inflammation and edema on STIR images.

- Patients must be on a stable dose of prednisone equal to or less than 0.5 mg/kg/day
for 1 month prior to the study.

- Patients must be on at least 7.5 mg of methotrexate weekly or at least 75 mg of
azathioprine daily for at least 4 weeks prior to the study.

- Patients must not be on any other cytotoxic agents for at least 1 month prior to the

- Women of childbearing potential and men whose partners are of childbearing potential
must practice an acceptable form of contraception.

- No prior history of treatment with monoclonal antibodies, i.e. no prior history of
infliximab therapy.

- Patients with active disease despite previous treatment with at least one other
immunosuppressive agent and/or intolerable side effects: e.g. high-dose prednisone
(1 mg/kg/day), methotrexate 12.5 to 20 mg/wk, azathioprine 100-150 mg/day,
cyclosporineA 2-2.5 mg/kg/day and cyclophosphamide 1-2 mg/kg/day.


Patients with inclusion body myositis or cancer-related or drug-induced myopathy.

History of hepatitis or abnormal liver function tests which do not reflect muscle disease.

History of recurrent infections, any active acute or chronic infections requiring
antimicrobial therapy, or serious viral (e.g. Hepatitis B positivity, herpes zoster,
herpes simplex, HIV positivity, hepatitis C or A, CMV) or fungal infections such as
histoplasmosis, aspergillosis, coccidiodomycosis. Patients with positive PPD who have
cavitary lesions suspicious for active tuberculosis will be excluded. In addition,
patients with a positive PPD who decline INH prophylaxis will be excluded. Any patients
with suspected pneumonia, cellulitis, pneumocystis carini, and infection at central venous
catheter site will also be excluded.

Patients with suspicious lesions on chest radiography suggestive of an infectious or
neoplastic condition will be excluded.

Pregnant females, nursing mothers, or patients of childbearing age not practicing birth

Preexisting or coexisting malignancy other than basal cell carcinoma and localized
squamous cell carcinoma of the skin.

Patients who have not had any recent age-appropriate malignancy screen within the past 3
months who refuse to have said age-appropriate malignancy screening procedures prior to
the start of the study.

History of cerebrovascular accidents, seizure disorder, aseptic meningitis, transverse
myelitis, central nervous system demyelinating disease such as multiple sclerosis.

Confounding medical illness that in the judgment of the investigators pose added risk for
study participants (e.g. chronic lung or hematological disease).

Anemia requiring maintenance blood transfusions; leukopenia with WBC less than 3,000/ul or
absolute neutrophil count less than 2,000/ul; platelet count less than 100,000/ul on at
least two different occasions.

History of (or current) autoimmune hemolytic anemia.

Current anticoagulant therapy.

History of lupus erythematosus -(+)ANA: dsDNA, anti-Smith, anti-Ro/La and clinical
presentation consistent with lupus erythematosus.

Clotting/bleeding disorders - history of arterial or venous thrombosis, stroke,
miscarriages and presence of antiphospholipid antibodies, protein C or protein S
deficiency along with a compatible history of a thrombotic event.

History of psychiatric illness that in the opinion of psychiatric consultants would pose
an added risk for study participants.

History of uncontrolled diabetes mellitus.

Prior use of infliximab.

Current use of a TNF-blocking agent (patient has to be off for 4 weeks). Prior use of
etanercept is accepted so long as patient has been off of it for 4 weeks.

Allergy to murine-derived products.

Poor venous access.

History of live vaccinations within the past 3 months.

History of drug abuse within the past 5 years.

History of congestive heart failure.

Echocardiographic evidence of dilated or hypertrophic cardiomyopathy.

Echocardiographic evidence of valvular stenosis or regurgitation that in the judgment of
the physician poses a risk for congestive heart failure.

History of significant arrhythmia requiring pacing or cardioversion.

EKG or echocardiographic evidence of ventricular hypertrophy and clinical signs of
congestive heart failure.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Muscle strength

Outcome Time Frame:

16 weeks

Safety Issue:


Principal Investigator

Adam I Schiffenbauer, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Institute of Environmental Health Sciences (NIEHS)


United States: Federal Government

Study ID:




Start Date:

April 2002

Completion Date:

May 2010

Related Keywords:

  • Dermatomyositis
  • Polymyositis
  • Muscle Weakness
  • Muscle Biopsy
  • Gene Expression Profiling
  • MRI
  • Inflammation
  • Polymyositis
  • Dermatomyositis
  • Dermatomyositis
  • Polymyositis



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