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

Primary Purpose

Inflammatory Myopathy

Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Interleukin-2
ciclosporin and corticosteroid
Sponsored by
Peking University People's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Inflammatory Myopathy focused on measuring Interleukin-2, Cyclosporin A

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female >18 years of age at screening visits
  2. Diagnostics meet the 1975 Bohan recommendations
  3. Failed at least 3 months treatment with hydroxychloroquine;
  4. New onset patients or recurrent patients after reduction of medication
  5. 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.
  6. 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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Interleukin-2 and ciclosporin and corticosteroid

    ciclosporin and corticosteroid

    Arm Description

    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.

    Ciclosporin and corticosteroid will be administered according to the doctor's decision. All patients were followed up for 6 months.

    Outcomes

    Primary Outcome Measures

    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).

    Secondary Outcome Measures

    MMT-8
    MMT-8; a set of 8 designated muscles tested bilaterally [potential score 0 - 150]
    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.
    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).
    Safety and tolerability of interleukin-2 as assessed by incidence of adverse events reported and observed
    we will report frequency of adverse events
    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).
    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).
    Foxp3+Treg cells: change in percentage of total lymphocytes
    Treg refers to regulatory T cells

    Full Information

    First Posted
    January 19, 2020
    Last Updated
    January 22, 2020
    Sponsor
    Peking University People's Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04237987
    Brief Title
    Low-dose Interleukin-2 in Combination With Standard Therapy on Idiopathic Inflammatory Myopathy
    Official Title
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2020
    Overall Recruitment Status
    Unknown status
    Study Start Date
    January 21, 2020 (Anticipated)
    Primary Completion Date
    January 8, 2021 (Anticipated)
    Study Completion Date
    April 8, 2021 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Peking University People's Hospital

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No

    5. Study Description

    Brief Summary
    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
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Inflammatory Myopathy
    Keywords
    Interleukin-2, Cyclosporin A

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    Participant
    Allocation
    Randomized
    Enrollment
    20 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Interleukin-2 and ciclosporin and corticosteroid
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    ciclosporin and corticosteroid
    Arm Type
    Active Comparator
    Arm Description
    Ciclosporin and corticosteroid will be administered according to the doctor's decision. All patients were followed up for 6 months.
    Intervention Type
    Drug
    Intervention Name(s)
    Interleukin-2
    Other Intervention Name(s)
    Recombinant Human Interleukin-2
    Intervention Description
    Interleukin-2 was produced by Beijing Shuanglu Pharmaceutical Co., Ltd
    Intervention Type
    Drug
    Intervention Name(s)
    ciclosporin and corticosteroid
    Intervention Description
    ciclosporin and corticosteroid
    Primary Outcome Measure Information:
    Title
    Proportion of subjects meeting the definition of improvement (DOI)
    Description
    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).
    Time Frame
    week 12
    Secondary Outcome Measure Information:
    Title
    MMT-8
    Description
    MMT-8; a set of 8 designated muscles tested bilaterally [potential score 0 - 150]
    Time Frame
    week12 and week 24
    Title
    CDASI activity score
    Description
    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.
    Time Frame
    week12 and week 24
    Title
    Physician's Global Disease Activity VAS
    Description
    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).
    Time Frame
    week 12 and week 24
    Title
    Safety and tolerability of interleukin-2 as assessed by incidence of adverse events reported and observed
    Description
    we will report frequency of adverse events
    Time Frame
    up tp 24 weeks
    Title
    Patient's Global Disease Activity VAS
    Description
    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).
    Time Frame
    week 12 and week 24
    Title
    Proportion of subjects meeting the definition of improvement (DOI)
    Description
    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).
    Time Frame
    week12 and week 24
    Title
    Foxp3+Treg cells: change in percentage of total lymphocytes
    Description
    Treg refers to regulatory T cells
    Time Frame
    week 12

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    MIAO MIAO
    Phone
    8618810024336
    Email
    miao18734897489@126.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Jing He
    Phone
    8618611707347
    Email
    hejing1105@126.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Zhanguo Li
    Organizational Affiliation
    Peking University Institute of Rheuamotology and Immunology
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    327194
    Citation
    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.
    Results Reference
    result

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

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