Ignite Creation Date:
2024-05-05 @ 11:25 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00033891
Status:
COMPLETED
Last Update Posted:
2019-12-03
First Post:
2002-04-11
Brief Title:
Infliximab Remicade to Treat Dermatomyositis and Polymyositis
Sponsor:
National Institute of Arthritis and Musculoskeletal and Skin Diseases NIAMS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Randomized Double-Blind Placebo-Controlled Trial of Infliximab in Patients With Dermatomyositis and Polymyositis
Status:
COMPLETED
Status Verified Date:
2019-02-25
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will examine whether infliximab Remicade 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 mgkg 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 mgkg body weight or 10mgkg 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 mgkg or 10 mgkg body weight of infliximab on week 16 while those patients who were previously on 3 mgkg 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
Blood tests every week to look for antibodies seen with muscle inflammation Some of the blood samples will be stored for later testing including genetic studies to find genetic differences related to inflammation
Skin test for tuberculosis
Chest x-rays at the beginning of the study if a recent one is not available and again at weeks 16 and 40 to look for active infection detect signs of past exposure or infection with diseases such as tuberculosis and assess the presence of lung disease that might be related to the myositis
MRI usually of the legs at the beginning of the study and again at weeks 16 and 40 to measure disease activity and extent of muscle involvement This will also give an idea of the response to treatment This test uses a magnetic field and radio waves to produce images of body tissues During the procedure the patient lies on a bed surrounded by a metal cylinder the scanner
Muscle biopsy at the beginning of the study to diagnose muscle inflammation and again at week 16 to evaluate the response to treatment
Electromyography if the patient has not had an EMG previously For this test small needles are inserted into the muscle to assess the electrical activity of the muscle
HIV test
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
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 mgkg 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 mgkg body weight or 10mgkg 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 mgkg or 10 mgkg body weight of infliximab on week 16 while those patients who were previously on 3 mgkg 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
Blood tests every week to look for antibodies seen with muscle inflammation Some of the blood samples will be stored for later testing including genetic studies to find genetic differences related to inflammation
Skin test for tuberculosis
Chest x-rays at the beginning of the study if a recent one is not available and again at weeks 16 and 40 to look for active infection detect signs of past exposure or infection with diseases such as tuberculosis and assess the presence of lung disease that might be related to the myositis
MRI usually of the legs at the beginning of the study and again at weeks 16 and 40 to measure disease activity and extent of muscle involvement This will also give an idea of the response to treatment This test uses a magnetic field and radio waves to produce images of body tissues During the procedure the patient lies on a bed surrounded by a metal cylinder the scanner
Muscle biopsy at the beginning of the study to diagnose muscle inflammation and again at week 16 to evaluate the response to treatment
Electromyography if the patient has not had an EMG previously For this test small needles are inserted into the muscle to assess the electrical activity of the muscle
HIV test
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
Detailed Description:
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 IgG1 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 11 ratio into 2 groups placebo vs infliximab at 5 mgkg 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 ie placebo or infliximab at 5 mgkg body weight at weeks 22 30 and 38 Placebo non-responders will be given infliximab at 5 mgkg body weight in an open label fashion at weeks 16 18 22 30 and 38 Patients who were initially on 5 mgkg body weight of infliximab who failed to respond based on the criteria set will be placed on infliximab at 75 mgkg 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 02-AR-0156 | None | None | None |