Rituximab Therapy in Refractory Adult and Juvenile Idiopathic Inflammatory Myopathy (IIM)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 200
- 试验地点
- 31
- 主要终点
- Comparison Between the Time to Improvement Between the Two Groups of IIM (Idiopathic Inflammatory Myopathy) Patients
研究概览
简要总结
Rituximab is a man-made antibody used to treat certain types of cancer. This study will determine whether rituximab is an effective treatment for adult and pediatric patients with dermatomyositis or polymyositis.
Study hypotheses: 1) The time to improvement in Group A patients (receiving rituximab first) will occur significantly earlier than in Group B patients (receiving rituximab later). 2) The proportion of patients improved at Week 8 of the treatment phase will be significantly greater in Group A than in Group B.
详细描述
Rituximab is a chimeric, murine-human, genetically engineered monoclonal antibody directed against the CD20 (cluster of differentiation antigen 20) antigen found on the surface of B-lymphocytes and is known to deplete B cells when administered intravenously. It is approved to treat non-Hodgkin's lymphoma. Rituximab has been used for autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and immune-mediated hematologic disorders. It has also been studied and used in small numbers of patients with myositis. This study will evaluate the efficacy of rituximab in treating refractory adult and pediatric patients with dermatomyositis and adult polymyositis.
A patient's participation in this study will last approximately 45 weeks. At screening, participants will have a physical exam, muscle strength assessment, an electrocardiogram, and blood and urine collection; they will also be asked to complete several questionnaires. All participants will receive 2 infusions of rituximab and 2 infusions of placebo. Participants will be randomly assigned to one of two groups. Group A will receive rituximab at Weeks 0 and 1 and placebo at Weeks 8 and 9. Group B will receive placebo at Weeks 0 and 1 and rituximab at Weeks 8 and 9. Each infusion will be given on an outpatient basis over a minimum of approximately 5 hours' time.
There will be a total of 14 study visits. All participants will visit the outpatient clinic at selected time points for muscle strength testing, a physical exam, disease activity measurements, and blood collection. During the study, participants will be monitored closely for improvement or worsening of their disease and for serious drug related side effects. Some participants will be asked if they are willing to undergo 2 muscle biopsy procedures, 1 prior to receiving study medication and 1 after receiving study medication, to determine the effects of rituximab on muscle tissue.
If a participant is unable to locate a near-by clinical center, the adult and pediatric centers at the National Institute of Health located in Bethesda, Maryland have funds available to assist with travel costs.
NIH SUB-STUDY: "Rituximab to Treat Dermatomyositis and Polymyositis"
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 5 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults with definite or probable dermatomyositis or polymyositis and pediatric patients five years of age and over with definite or probable juvenile dermatomyositis (JDM) by Bohan and Peter criteria. Diagnosis of JDM based on an age of onset (i.e., first symptom of myositis or dermatomyositis rash) is less 18 years of age
- •Refractory myositis, defined by intolerance to or inadequate response to corticosteroids plus an adequate regime of at least one other immunosuppressive agent. Intolerance is defined as side effects that require discontinuation of the medication or an underlying condition that precludes further use of the medication.
- •Baseline manual muscle testing which is based on a maximum MMT-8 (Manual Muscle Test) score of 150:Adult subjects with dermatomyositis (DM) or polymyositis (PM) must have a score that is no greater than 125/150 in conjunction with 2 other abnormal core set measures.
- •Subjects with a diagnosis of Juvenile Dermatomyositis (JDM) must meet either of the following criteria:
- •An MMT-8 (Manual Muscle Test) score that is no greater than 125/150 in conjunction with 2 other abnormal core set measures.
- •If MMT (Manual Muscle Test) score is greater than 125/150 the patient MUST meet at least 3 abnormal core set measures.
- •Background therapy with at least 1 non-corticosteroid immunosuppressive agent at a stable dose for at least 6 weeks prior to screening
- •Able and willing to complete self-report questionnaires. Parents of pediatric participants will be required to complete the questionnaires on behalf of their children.
- •Willing to use acceptable forms of contraception for the duration of the study for patients of reproductive potential.
- •Parent willing to provide informed consent, if applicable
- •Willing to forgo immunization with a live vaccine for the duration of the study
排除标准
- •Drug-induced myositis. Patients who have myositis or myopathic syndromes caused by taking medications known to induce myositis-like syndromes, including but not limited to statin agents, fibric acid derivatives, colchicine, and hydroxychloroquine.
- •Juvenile polymyositis
- •Inclusion body myositis
- •Cancer-associated myositis, defined as the diagnosis of myositis within 2 years of the diagnosis of cancer. Patients with basal or squamous cell skin cancer or carcinoma in situ of the cervix are not excluded, if it has been at least 5 years since excision.
- •Myositis in overlap with another connective tissue disease that may preclude the accurate assessment of a treatment response
- •Live viral vaccine within 4 weeks prior to study entry
- •Any joint disease or other musculoskeletal condition that may interfere with muscle strength testing
- •Known hypersensitivity to mouse proteins
- •Any concomitant or life-threatening non-myositis illness that, in the opinion of the investigator, may interfere with the study
- •Known or suspected history of drug or alcohol abuse within the last 6 months prior to study entry, as determined by medical record or patient interview
- •Anticipated poor compliance with study requirements
- •Participation in another clinical trial within 30 days prior to screening
- •Any history or evidence of any severe illness or other condition that, in the opinion of the investigator, may interfere with the study
- •Previously received rituximab
- •Evidence of prior infection with hepatitis B or hepatitis C virus
- •Initiation of an exercise program within 4 weeks of screening OR initiation of an exercise program during the study
- •Consumed any creatine-containing, over-the-counter products in the form of dietary supplements 30 days prior to screening visit and for the duration of the study
研究组 & 干预措施
Adult Study Group 1
Refractory adult polymyositis patients who will receive rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A)
干预措施: Rituximab (Drug)
Adult Study Group 1
Refractory adult polymyositis patients who will receive rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A)
干预措施: Placebo (Drug)
Adult Study Group 2
Refractory adult polymyositis patients who will receive placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B)
干预措施: Rituximab (Drug)
Adult Study Group 2
Refractory adult polymyositis patients who will receive placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B)
干预措施: Placebo (Drug)
Adult Study Group 3
Adult dermatomyositis patients who will receive rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A)
干预措施: Rituximab (Drug)
Adult Study Group 3
Adult dermatomyositis patients who will receive rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A)
干预措施: Placebo (Drug)
Adult Study Group 4
Adult dermatomyositis patients who will receive placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B)
干预措施: Rituximab (Drug)
Adult Study Group 4
Adult dermatomyositis patients who will receive placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B)
干预措施: Placebo (Drug)
JDM Study Group 1
Refractory juvenile dermatomyositis patients who will receive rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A)
干预措施: Rituximab (Drug)
JDM Study Group 1
Refractory juvenile dermatomyositis patients who will receive rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A)
干预措施: Placebo (Drug)
JDM Study Group 2
Refractory juvenile dermatomyositis patients who will receive placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B)
干预措施: Rituximab (Drug)
JDM Study Group 2
Refractory juvenile dermatomyositis patients who will receive placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B)
干预措施: Placebo (Drug)
结局指标
主要结局
Comparison Between the Time to Improvement Between the Two Groups of IIM (Idiopathic Inflammatory Myopathy) Patients
时间窗: Week 44 of treatment phase
The Definition of Improvement for both adult and pediatric patients will be: 3 of any of the 6 core set measures improved by ≥ 20%, with no more than 2 of the core set measures worsening by ≥25% (worsening measure cannot include the MMT) at two consecutive visits. Of note, the MMT could not be one of the worsening measures. Core Set Measures Included: 1. Manual Muscle Testing (MMT)- Muscle Strength 2. Physician Global Disease Activity VAS Score 3. Health Assessment Questionnaire Index Score - Physical Function 4. Patient Global Assessment of Disease Activity VAS score 5. Extramuscular Activity - Myositis Disease Activity Assessment Tool 6. 2 or more elevated muscle enzymes (Aldolase, CK, AST, ALT, and LDH)
次要结局
- Response Rates (Proportion of Improved Patients) Between Groups A (Rituximab Wks 0 and 1) and B (Rituximab Wks 8 and 9) at Week 8(Week 8 of the treatment phase)
- 20% Improvement in Manual Muscle Testing (MMT) Over Baseline on Two Consecutive Time Points (Muscle is the Primary Organ of Involvement, and MMT is the One Objective Measurement of the Definition of Improvement [DOI])(Week 44 of treatment phase)
研究者
Chester Oddis
MD, Professor of Medicine, University of Pittsburgh, Division of Rheumatology and Clinical Immunology
University of Pittsburgh