Low-dose Interleukin-2 in Combination With Standard Therapy on Idiopathic Inflammatory Myopathy

Study Overview
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Brief Summary
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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)

Detailed Description
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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.

Official Title
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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

Conditions
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Inflammatory Myopathy

Intervention / Treatment
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* Drug: Interleukin-2
* Drug: ciclosporin and corticosteroid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 5. 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). Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interleukin-2 and ciclosporin and corticosteroid<br>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. | Drug: Interleukin-2<br>* Interleukin-2 was produced by Beijing Shuanglu Pharmaceutical Co., Ltd<br>* Other names: Recombinant Human Interleukin-2;Drug: ciclosporin and corticosteroid<br>* ciclosporin and corticosteroid<br>|
| Active Comparator: ciclosporin and corticosteroid<br>Ciclosporin and corticosteroid will be administered according to the doctor's decision. All patients were followed up for 6 months. | Drug: ciclosporin and corticosteroid<br>* ciclosporin and corticosteroid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects meeting the definition of improvement (DOI) | 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). | week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MMT-8 | MMT-8; a set of 8 designated muscles tested bilaterally [potential score 0 - 150] | week12 and week 24 | 
| CDASI activity score | The CDASI is a clinician-scored single page instrument that separately measures activity and damage in the skin of DM patients for use in clinical practice or clinical/therapeutic studies. Disease involvement in 15 different anatomical locations is rated using three activity (erythema, scale, erosion/ulceration) and two damage (poikiloderma, calcinosis) measures. The presence and severity of Gottron's papules, periungual changes and alopecia are also captured. Disease activity is scored from 0 to 100; higher scores indicate greater disease severity. | week12 and week 24 | 
| Physician's Global Disease Activity VAS | Physician's Global Disease Activity (10 cm VAS assessing global disease activity from No evidence of disease activity to Extremely active or severe disease activity; Disease Activity being defined as potentially reversible pathology or physiology resulting from the myositis). | week 12 and week 24 | 
| Safety and tolerability of interleukin-2 as assessed by incidence of adverse events reported and observed | we will report frequency of adverse events | up tp 24 weeks | 
| Patient's Global Disease Activity VAS | Patient's Global Disease Activity (10 cm VAS assessing global disease activity from No evidence of disease activity to Extremely active or severe disease activity; Disease Activity being defined as potentially reversible pathology or physiology resulting from the myositis). | week 12 and week 24 | 
| Proportion of subjects meeting the definition of improvement (DOI) | The primary outcome will be to compare the proportion of subjects meeting the definition of improvement (DOI) at visits 3 after the 3-month treatment period. The DOI for this trial is a composite utilizing the six core set measures (CSM): 3 of 6 CSM improved by ≥ 20%, with no more than 2 CSM worsening by ≥25% (a worsening measure cannot be the MMT). | week12 and week 24 | 
| Foxp3+Treg cells: change in percentage of total lymphocytes | Treg refers to regulatory T cells | week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Interleukin-2, Cyclosporin A