Interleukin-2 on Active Dermatomyositis

Official title

Therapeutic Effect of Interleukin-2 on Active Dermatomyositis: A Multicenter, Randomised, Double-blind, Placebo-controlled Trial

Overview

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.

Interventions

• Drug Interleukin-2
  low dose interleukin-2 injected subcutaneously, at a dose of 1 x 10\~6 IU once every other day, for 6 months.

Primary outcome measures

• Proportion of subjects achieving minimal improvement (TIS≥20). [Time frame: week 12]

Secondary outcome measures (12)

• MMT-8 (Manual Muscle Testing), (potential score 0 - 80); [Time frame: week12 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); [Time frame: week12 and 24]
• Physician's Global Disease Activity VAS, (potential score 0 - 10); [Time frame: week12 and 24]
• Patient's Global Disease Activity VAS, (potential score 0 - 80); [Time frame: week 12 and 24]
• Health assessment question, (potential score 0 - 3); [Time frame: week 12 and 24]
• Myositis disease activity assessment tool (MDAAT) - 2005, VERSION 2 [Time frame: week 12 and 24]
• CD4 T cells [Time frame: week 12 and 24]
• Serum cytokines [Time frame: week 12 and 24]
• glucocorticoid dosage [Time frame: week 12 and 24]
• Rate of Participants with adverse effects associated with experimental drugs [Time frame: up to 24 weeks]
• Proportion of subjects meeting the definition of improvement (DOI) [Time frame: week12 and 24]
• Number of subjects achieving minimal improvement (TIS≥20). [Time frame: week 24]

Eligibility criteria

Inclusion criteria

• 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 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.
• 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).

Exclusion criteria

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 < 60.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Peking university people's hospital — Beijing

Identifiers

NCT: NCT05495321 · IIMIL2

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗