A Randomized Controlled Trial to Evaluate the Efficacy and Safety of Low-dose Interleukin-2 in Combination With Standard Therapy Compared to Standard Therapy Alone in Adults With Active Idiopathic Inflammatory Myopathy
试验速览
- 阶段
- 2 期
- 入组人数
- 20
- 主要终点
- Proportion of subjects meeting the definition of improvement (DOI)
研究概览
简要总结
This study aims to explore the clinical and immunological efficacy of low-dose Interleukin-2 (IL-2) and cyclosporin a (CSA) on idiopathic inflammatory myopathy (IIM)
详细描述
The investigators designed a radomized control study. Adults with active IIM will be enrolled. IIM is defined as Dermatomyositis (DM) or Polymyositis (PM), meeting the Bohan & Peter (1975) diagnostic criteria for definite or probable DM or PM. Patients will be randomly divided into 2 groups arranged by registration order. One million units of Recombinant Human Interleukin-2 (rhIL-2) was administered subcutaneously every other day for 3 months. All patients were followed up for 3 months after withdraw of IL-2.
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female >18 years of age at screening visits
- •Diagnostics meet the 1975 Bohan recommendations
- •Failed at least 3 months treatment with hydroxychloroquine;
- •New onset patients or recurrent patients after reduction of medication
- •The patient must be informed in writing of the consent to participate in the trial and the patient is expected to be able to comply with the requirements of the study follow-up plan and other protocols.
- •Active Disease means active skin disease or active muscle myositis. Active skin disease as defined by a CDASI score of at least
- •The active muscle myositis defined by the baseline hand muscle strength test (MMT-8) does not exceed 142/150, wtih at least 2 additional CSMs meet the criteria specified below:
- •Patients Globle Assessment, the minimum value of 10 cm visual analog scale (VAS) is 2.0 cm
- •Physicians Globle Assessment, the minimum value on the 10 cm VAS scale is 2.0 cm
- •Health Assessment Questionnaire (HAQ) Disability Index, with a minimum value of 0.25
- •At least one muscle enzyme [including creatine kinase (CK), aldolase, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] High, the lowest level is 1.3 x upper limit normal
- •Global Extra-muscle Disease Activity Score, with a minimum of 1.0 cm on the 10 cm VAS scale [This measure is a comprehensive assessment by the physician based on an assessment of the physique, skin, bone, gastrointestinal, lung and heart scale activity scores Myositis Disease Activity Assessment Tool (MDAAT).
排除标准
- •Any subject meeting any of the following criteria should be excluded:
- •Use rituximab or other monoclonal antibodies within 6 months.
- •Received high doses of glucocorticoid (>0.5 mg/kg/d) within 1 month.
- •Serious complications: including heart failure (≥ New York Heart Association (NYHA) class III), renal insufficiency (creatinine clearance ≤ 30 ml/min), liver dysfunction (serum ALT or AST greater than three times the upper limit of normal, or total bilirubin greater than Normal upper limit)
- •Other serious, progressive or uncontrollable hematology, gastrointestinal, endocrine, pulmonary, cardiac, neurological or brain disorders (including demyelinating diseases such as multiple sclerosis).
- •Known allergies, hyperreactivity or intolerance of IL-2 or its excipients.
- •Have a serious infection needing hospitalization (including but not limited to hepatitis, pneumonia, bacteremia, pyelonephritis, EB virus, tuberculosis infection), or use intravenous antibiotics to treat infection in 2 months before the enrollment.
- •Chest imaging showed abnormalities in malignant tumors or current active infections (including tuberculosis) within 3 months prior to the first use of the study drug.
- •Infection with HIV (HIV antibody positive serology) or hepatitis C (Hep C antibody positive serology). If seropositive, it is recommended to consult a doctor who has expertise in treating HIV or hepatitis C virus infection.
- •Any known history of malignancy in the past 5 years (except for non-melanoma skin cancer, non-melanoma skin cancer or cervical tumor without recurrence within 3 months after surgical cure prior to the first study preparation).
- •Uncontrolled mental or emotional disorders, including a history of drug and alcohol abuse over the past 3 years, may hinder the successful completion of the study.
- •Accept or expect to receive any live virus or bacterial vaccination within 3 months prior to the first injection of the study agent, during the study period, or within 4 months after the last injection of the study agent. Bacillus Calmette - Guerin (BCG) vaccine was inoculated within 12 months after screening.
- •Pregnant, lactating women (WCBP) are reluctant to use medically approved contraceptives during treatment and 12 months after treatment.
- •Men whose partners have fertility potential but are reluctant to use appropriate medically-accepted contraceptives during treatment and 12 months after the study.
- •Adolescents with DM or PM, myositis overlaps with another connective tissue disease.
研究组 & 干预措施
Interleukin-2 and ciclosporin and corticosteroid
One million units of Recombinant Human Interleukin-2 (IL-2) will be administered subcutaneously every other day for 3 months. Ciclosporin and corticosteroid will be administered according to the doctor's decision. All patients were followed up for 3 months after withdraw of IL-2.
干预措施: Interleukin-2 (Drug)
Interleukin-2 and ciclosporin and corticosteroid
One million units of Recombinant Human Interleukin-2 (IL-2) will be administered subcutaneously every other day for 3 months. Ciclosporin and corticosteroid will be administered according to the doctor's decision. All patients were followed up for 3 months after withdraw of IL-2.
干预措施: ciclosporin and corticosteroid (Drug)
ciclosporin and corticosteroid
Ciclosporin and corticosteroid will be administered according to the doctor's decision. All patients were followed up for 6 months.
干预措施: ciclosporin and corticosteroid (Drug)
结局指标
主要结局
Proportion of subjects meeting the definition of improvement (DOI)
时间窗: week 12
The primary outcome will be to compare the proportion of subjects meeting the definition of improvement (DOI) at visits 2 through 7 during the 6-month treatment period between the treatment and placebo arms. The DOI for this trial is a composite utilizing the six CSM: 3 of 6 CSM improved by ≥ 20%, with no more than 2 CSM worsening by ≥25% (a worsening measure cannot be the MMT).
次要结局
- MMT-8(week12 and week 24)
- CDASI activity score(week12 and week 24)
- Foxp3+Treg cells: change in percentage of total lymphocytes(week 12)
- Physician's Global Disease Activity VAS(week 12 and week 24)
- Safety and tolerability of interleukin-2 as assessed by incidence of adverse events reported and observed(up tp 24 weeks)
- Patient's Global Disease Activity VAS(week 12 and week 24)
- Proportion of subjects meeting the definition of improvement (DOI)(week12 and week 24)