Clinical trial NCT05495321: Interleukin-2 on Active Dermatomyositis
Official title: Therapeutic Effect of Interleukin-2 on Active Dermatomyositis: A Multicenter, Randomised, Double-blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE3
Conditions: Dermatomyositis
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2022-08-10
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this paper is to explore the effect of low-dose IL-2 on refractory dermatomyositis and immunological indexes.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Age 18-75 years old (including 18 and 75 years old);
2. The diagnosis of dermatomyositis conforms to Bohan/Peter Recommendation in 1975 or EULAR/ACR Classification Standard in 2017.

   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:
   * 1. patients global assessment (PGA), the minimum value of 10 cm visual analog scale (VAS) is 2.0 cm
   * 2. Physicians global assessment (PhGA), the minimum value on the 10 cm VAS scale is 2.0 cm
   * 3. Health Assessment Questionnaire (HAQ), with a minimum value of 0.25
   * 4. 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
   * 5. Global Extra-muscle Disease Activity Score, with a minimum of 1.0 cm on the 10 cm VAS scale \[This measure is a comprehensive assessment by the physician based on an assessment of the physique, skin, bone, gastrointestinal, lung and heart scale activity scores,named Myositis Disease Activity Assessment Tool (MDAAT)\].
   * 6. Manual Muscle Testing (MMT-8) no greater than 125/150.
3. 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.
4. 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.
5. Agree to adopt effective contraceptive measures during the study period (women of childbearing age).

Exclusion Criteria:

Any subject meeting any of the following criteria should be excluded:

1. Received intravenous glucocorticoid (\> 1 mg/kg/d) within 4 weeks;
2. 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 \< 60.
3. Dermatomyositis patients with other connective tissue diseases or tumors;
4. Allergic constitution or allergic to multiple drugs;
5. 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;
6. Those who are positive for hepatitis B surface antigen or hepatitis C antibody;
7. Persons with mental illness or other reasons who cannot cooperate with treatment.

Primary outcomes:
measure: Proportion of subjects achieving minimal improvement (TIS≥20).
timeFrame: week 12
Secondary outcomes:
measure: MMT-8 (Manual Muscle Testing), (potential score 0 - 80);
timeFrame: week12 and 24
measure: 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);
timeFrame: week12 and 24
measure: Physician's Global Disease Activity VAS, (potential score 0 - 10);
timeFrame: week12 and 24
measure: Patient's Global Disease Activity VAS, (potential score 0 - 80);
timeFrame: week 12 and 24
measure: Health assessment question, (potential score 0 - 3);
timeFrame: week 12 and 24
measure: Myositis disease activity assessment tool (MDAAT) - 2005, VERSION 2
timeFrame: week 12 and 24
measure: CD4 T cells
timeFrame: week 12 and 24
measure: Serum cytokines
timeFrame: week 12 and 24
measure: glucocorticoid dosage
timeFrame: week 12 and 24
measure: Rate of Participants with adverse effects associated with experimental drugs
timeFrame: up to 24 weeks
measure: Proportion of subjects meeting the definition of improvement (DOI)
timeFrame: week12 and 24
measure: Number of subjects achieving minimal improvement (TIS≥20).
timeFrame: week 24
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking university people's hospital
state: Beijing
Study officials:
affiliation: Peking University People's Hospital
name: Zhanguo Li
role: STUDY_DIRECTOR
References: