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Sponsored by: |
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) |
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Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00033891 |
This study will examine whether infliximab (Remicade® (Registered Trademark)) is safe and effective for the treatment of dermatomyositis and polymyositis. Infliximab blocks the effect of a protein called tumor necrosis factor (TNF), which is associated with harmful inflammation in many diseases.
Patients 18 years of age and older with active dermatomyositis or polymyositis that does not respond adequately to treatment with methotrexate and corticosteroids may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood and urine tests, chest x-ray, pulmonary function test, skin test for tuberculosis, HIV test, electromyography (described below), manual muscle testing, and functional assessments. Magnetic resonance imaging (described below) will be done to assess the degree and location of inflammation in the involved limbs. An electrocardiogram and echocardiogram will be done if recent ones are not available. Patients who qualify for the study will be asked to undergo two muscle biopsies (surgical removal and analysis of small pieces of muscle tissue), one before initiation of treatment and another on the 16th week .
Participants will be randomly assigned to receive either 3 mg/kg body weight of infliximab or a placebo (inactive substance) by infusion through a vein over 2 hours. The infusions will be given at the beginning of the treatment period (week 0) and at weeks 2, 6 and 14. At week 16, strength will be assessed by manual muscle testing. Patients who improved with treatment will continue with the same infusion dose on weeks 18, 22, 30, and 38. Those who do not improve will be assigned by random allocation to receive either 5 mg/kg body weight or 10/mg/kg body weight of infliximab on weeks 18, 22, 30 and 38. Those who did not improve who were previously on the placebo infusion will receive an extra dose of either 5 mg/kg or 10 mg/kg body weight of infliximab on week 16, while those patients who were previously on 3 mg/kg body weight of infliximab who failed to meet the improvement criteria will receive an infusion containing no medication on week 16. Patients will be admitted to the hospital for infusions at weeks 0, 14 and 38; the rest will be given on an outpatient basis. After the 38th week, all infusions will be stopped and patients will be assessed on the 40th week.
Participants will undergo some or all of the following tests and evaluations during treatment:
Patients whose disease worsen with treatment or who develop serious drug-related side effects will be taken off the study and referred back to their primary care physician for further therapy. Patients who improve will be referred back to their primary physician at the end of the study for possible continued treatment. Participants will be asked to return for follow-up visits every 6 weeks for a total of 30 weeks to monitor long-term effects of the drug
Condition | Intervention | Phase |
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Dermatomyositis Polymyositis |
Drug: Infliximab |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Crossover Assignment, Efficacy Study |
Official Title: | A Randomized, Double-Blind, Placebo-Controlled Trial of Infliximab In Patients With Dermatomyositis and Polymyositis |
Estimated Enrollment: | 28 |
Study Start Date: | April 2002 |
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 week 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 are 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.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Must be at least 18 years of age.
Diagnosis of probable or definite polymyositis or dermatomyositis as defined by Bohan and Peter:
i. Symmetrical proximal muscle weakness;
ii. Muscle biopsy abnormalities at some time during their disease:
iii. Elevation of serum creatine phosphokinase (CPK), Transaminases, lactic dehydrogenase (LDH) or aldolase activity;
iv. Electromyography changes:
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
EXCLUSION CRITERIA:
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 control.
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.
Responsible Party: | National Institutes of Health ( Paul H. Plotz, M.D./National Institute of Arthritis and Musculoskeletal and Skin Diseases ) |
Study ID Numbers: | 020156, 02-AR-0156 |
Study First Received: | April 11, 2002 |
Last Updated: | November 21, 2008 |
ClinicalTrials.gov Identifier: | NCT00033891 |
Health Authority: | United States: Federal Government |
Muscle Weakness Muscle Biopsy Gene Expression Profiling MRI |
Inflammation Polymyositis Dermatomyositis |
Skin Diseases Asthenia Infliximab Muscle Weakness Inflammation Myositis Dermatomyositis |
Muscular Diseases Musculoskeletal Diseases Neuromuscular Diseases Polymyositis Connective Tissue Diseases Idiopathic myopathy |
Anti-Inflammatory Agents Therapeutic Uses Nervous System Diseases Gastrointestinal Agents |
Antirheumatic Agents Dermatologic Agents Pharmacologic Actions |