Therapeutic Effect of Interleukin-2 on Active Dermatomyositis: A Multicenter, Randomised, Double-blind, Placebo-controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- Enrolling By Invitation
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- Proportion of subjects achieving minimal improvement (TIS≥20).
研究概览
简要总结
The purpose of this paper is to explore the effect of low-dose IL-2 on refractory dermatomyositis and immunological indexes.
详细描述
A randomized, double-blind, placebo-controlled, multicenter clinical trial was designed. Patients were treated with low-dose IL-2 regularly to explore its efficacy and safety. The improvement of clinical and laboratory indexes was evaluated. Changes of immune cell subsets and cytokines were monitored.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-75 years old (including 18 and 75 years old);
- •The diagnosis of dermatomyositis conforms to Bohan/Peter Recommendation in 1975 or EULAR/ACR Classification Standard in
- •Active myositis was defined by baseline Manual Muscle Testing (MMT-8) no greater than 125/150 and at least two additional abnormal CSMs. To allow the enrolment of patients with active DM with a moderate to severe rash who may not meet the MMT-8 criterion noted above, patients with DM could be enrolled if their cutaneous VAS score on the Myositis Disease Activity Assessment Tool (MDAAT) was ≥3cm on the 10cm VAS scale and at least three of the five CSMs were abnormal (excluding the MMT-8).
- •Abnormal CSMs include:
- •patients global assessment (PGA), the minimum value of 10 cm visual analog scale (VAS) is 2.0 cm
- •Physicians global assessment (PhGA), the minimum value on the 10 cm VAS scale is 2.0 cm
- •Health Assessment Questionnaire (HAQ), 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,named Myositis Disease Activity Assessment Tool (MDAAT)].
- •Manual Muscle Testing (MMT-8) no greater than 125/
- •The dose of glucocorticoid (equivalent to prednisone) was less than 0.5mg/kg/d within 4 weeks before joining the group, and/or there were no new immunosuppressants (cyclophosphamide, mycophenolate mofetil, cyclosporine, tacrolimus, azathioprine, methotrexate, etc.) within 12 weeks, and the dose was stable for 4 weeks.
- •Voluntary signing of informed consent: When participating in the trial, the patient must be given a written notice of consent, and hope that the patient can comply with the requirements of the study follow-up plan and other protocols.
- •Agree to adopt effective contraceptive measures during the study period (women of childbearing age).
排除标准
- •Any subject meeting any of the following criteria should be excluded:
- •Received intravenous glucocorticoid (> 1 mg/kg/d) within 4 weeks;
- •Serious complications: including (1). heart failure (≥ NYHA III); (2). renal insufficiency (creatinine clearance rate ≤30 ml/min); (3). liver insufficiency (excluding serum ALT or AST caused by dermatomyositis, or total bilirubin greater than normal upper limit), (4). hemoglobin < 80g/L, E. platelet count <
- •Dermatomyositis patients with other connective tissue diseases or tumors;
- •Allergic constitution or allergic to multiple drugs;
- •Those who are in the period of acute and chronic infection (including but not limited to hepatitis, pneumonia, bacteremia, pyelonephritis, Epstein-Barr virus, tuberculosis infection), or are hospitalized for infection, or use intravenous antibiotics to treat infection 2 months before the first treatment, or have a history of active tuberculosis in the past;
- •Those who are positive for hepatitis B surface antigen or hepatitis C antibody;
- •Persons with mental illness or other reasons who cannot cooperate with treatment.
研究组 & 干预措施
low-dose IL-2
The first stage (double-blind treatment period): One million IU of IL-2 was injected subcutaneously once every other day for 12 weeks.
The second stage (open treatment period): One million IU of IL-2 was injected subcutaneously once every other day for 12 weeks.
干预措施: Interleukin-2 (Drug)
Placebo
The first stage (double-blind treatment period): Placebo was injected subcutaneously once every other day for 12 weeks.
The second stage (open treatment period): One million IU of IL-2 was injected subcutaneously once every other day for 12 weeks.
干预措施: Interleukin-2 (Drug)
结局指标
主要结局
Proportion of subjects achieving minimal improvement (TIS≥20).
时间窗: week 12
The primary outcome will be to compare the proportion of subjects achieving minimal improvement (TIS≥20). The TIS (total improvement score) is the sum of all 6 improvement scores associated with the change in each core set measure. A total improvement score of ≥20 represents minimal improvement, a score of ≥40 represents moderate improvement, and a score of ≥60 represents major improvement.
次要结局
- CD4 T cells(week 12 and 24)
- Serum cytokines(week 12 and 24)
- MMT-8 (Manual Muscle Testing), (potential score 0 - 80);(week12 and 24)
- Physician's Global Disease Activity VAS, (potential score 0 - 10);(week12 and 24)
- Myositis disease activity assessment tool (MDAAT) - 2005, VERSION 2(week 12 and 24)
- glucocorticoid dosage(week 12 and 24)
- Rate of Participants with adverse effects associated with experimental drugs(up to 24 weeks)
- Proportion of subjects meeting the definition of improvement (DOI)(week12 and 24)
- Number of subjects achieving minimal improvement (TIS≥20).(week 24)
- Patient's Global Disease Activity VAS, (potential score 0 - 80);(week 12 and 24)
- CDASI activity score (cutaneous dermatomyositis disease area and severity index), (potential score 0-100 for cutaneous dermatomyositis disease area and 0-32 for severity index);(week12 and 24)
- Health assessment question, (potential score 0 - 3);(week 12 and 24)
研究者
Zhanguo Li
professor
Peking University People's Hospital