Low-dose Interleukin-2 Treatment on Idiopathic Inflammatory Myopathy

This study aims to explore the clinical and immunological efficacy of low-dose Interleukin-2 (IL-2) on idiopathic inflammatory myopathy (IIM).

Study Overview

• Status: Unknown
• Conditions: Inflammatory Myopathy
• Intervention / Treatment: Drug: Interleukin-2

Detailed Description

The investigators designed a single center, open-label, prospective 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. 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.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Miao MIAO; Phone Number: +86 18810024336; Email: miao18734897489@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female >18 years of age at screening visits
2. Diagnostics meet the 1975 Bohan recommendations

3. Applying of glucocorticoids (≤0.5 mg/kg/d prednisone or equivalent doses of other hormones), DMARDs (eg methotrexate, hydroxychloroquine, azathioprine, morphine, Ester, leflunomide, cyclosporine, etc.) must be stable for 4 weeks and do not increase hormone doses or other immunosuppressive agents throughout the study. If the enrolled doctor plans to stop using the current immunosuppressant or glucocorticoid, the elution period needs to be followed before enrollment. Each drug needs to meet the following elution period

   • Glucocorticoid-2 weeks
   • Immunosuppressants (including methotrexate, azathioprine, cyclosporine, tacrolimus, leflunomide, mycophenolate mofetil) - 4 weeks
   • intravenous immunogloblin (IVIg) or cyclophosphamide - 2 months
   • Rituximab - 6 months
   • Other biological agents (infliximab, adalimumab, etanercept, anakinra, etc.) -12 weeks
4. 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.

5. 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:

1. Use rituximab or other monoclonal antibodies within 6 months.
2. Received high doses of glucocorticoid (>0.5 mg/kg/d) within 1 month.
3. 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)
4. Other serious, progressive or uncontrollable hematology, gastrointestinal, endocrine, pulmonary, cardiac, neurological or brain disorders (including demyelinating diseases such as multiple sclerosis).
5. Known allergies, hyperreactivity or intolerance of IL-2 or its excipients.
6. 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.
7. 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.
8. 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.
9. 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).
10. 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.
11. 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.
12. Pregnant, lactating women (WCBP) are reluctant to use medically approved contraceptives during treatment and 12 months after treatment.
13. Men whose partners have fertility potential but are reluctant to use appropriate medically-accepted contraceptives during treatment and 12 months after the study.
14. Adolescents with DM or PM, myositis overlaps with another connective tissue disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: interleukin-2; low dose interleukin-2 injected subcutaneously, at a dose of 1 x 10~6 IU/m2 once every other day, for 3 months.	Drug: Interleukin-2; low dose interleukin-2 injected subcutaneously, at a dose of 1 x 10~6 IU/m2 once every other day, for 3 months.; Other Names: Recombinant Human Interleukin-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Foxp3+Treg cells: change in percentage of total lymphocytes	Treg refers to regulatory T cells	week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
MMT-8	MMT-8; a set of 8 designated muscles tested bilaterally [potential score 0 - 150]	week12 and 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 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 24
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 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 24

Collaborators and Investigators

• Sponsor: Peking University People's Hospital

Publications and helpful links

General Publications

• Bohan A, Peter JB, Bowman RL, Pearson CM. Computer-assisted analysis of 153 patients with polymyositis and dermatomyositis. Medicine (Baltimore). 1977 Jul;56(4):255-86. doi: 10.1097/00005792-197707000-00001. No abstract available.
• Miao M, Li Y, Huang B, Chen J, Jin Y, Shao M, Zhang X, Sun X, He J, Li Z. Treatment of Active Idiopathic Inflammatory Myopathies by Low-Dose Interleukin-2: A Prospective Cohort Pilot Study. Rheumatol Ther. 2021 Jun;8(2):835-847. doi: 10.1007/s40744-021-00301-3. Epub 2021 Apr 14.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): August 30, 2019
• Primary Completion (ANTICIPATED): March 31, 2021
• Study Completion (ANTICIPATED): June 30, 2021

Study Registration Dates

• First Submitted: August 18, 2019
• First Submitted That Met QC Criteria: August 18, 2019
• First Posted (ACTUAL): August 20, 2019

Study Record Updates

• Last Update Posted (ACTUAL): August 28, 2019
• Last Update Submitted That Met QC Criteria: August 26, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Muscular Diseases; Myositis; Physiological Effects of Drugs; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antineoplastic Agents; Aldesleukin; Interleukin-2
• Other Study ID Numbers: 2019-PHB089-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No