RCT of Tocilizumab for Anti-MDA5+DM

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-65
SponsorPeking Union Medical College Hospital

About this trial

The goal of this clinical trial is to learn if tocilizumab works to treat anti-MDA5+ dermatomyositis (anti-MDA5+DM) in adults. It will also learn about the safety of tocilizumab. The main questions it aims to answer are:

Does tocilizumab improve patients' clinical symptoms? Does tocilizumab improve patients' respiratory failure? What medical problems do participants have when taking tocilizumab? Researchers will compare tocilizumab to a placebo (a look-alike substance that contains no drug) to see if tocilizumab works to treat patients with anti-MDA5+ DM.

Participants will:

Take tocilizumab or a placebo every two weeks for 2 months Visit the clinic once every 2 weeks for checkups and tests

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥ 18 years and < 65 years; no gender restriction; total body weight ≥ 45 kg;

Diagnostic Criteria for Anti-MDA5-DM: Refer to the "2023 Chinese Expert Consensus on Diagnosis and Treatment of Anti-Melanoma Differentiation-Related Gene 5 Antibody-Positive Dermatomyositis in China." Dermatomyositis patients exhibiting one of the following manifestations-Gottron's papules, Gottron's rash, or erythema ab igne-along with positive serum anti-MDA5 antibodies, may be diagnosed with anti-MDA5-DM;

If patients have concomitant ILD, the following conditions must be met: i) Pulse oxygen saturation (SpO₂) ≥ 90% or PaO₂ ≥ 60 mmHg; ii) Pulmonary function tests showing forced vital capacity percentage of predicted (FVC%) ≥ 60% and carbon monoxide diffusion capacity percentage of predicted (DLco%) ≥ 40%; iii) High-resolution chest CT demonstrating pulmonary interstitial lesions involving < 50% of lung fields;

Patients must have received oral prednisone (< 1 mg/kg/day, or equivalent dose of other glucocorticoids) for ≥ 4 weeks prior to randomization;

Disqualifiers

1. Polymyositis, anti-synthetase syndrome, immune-mediated necrotizing myositis, or overlap myositis with other connective tissue diseases; 2. Patients with life-threatening complications, including but not limited to acute coronary syndrome (e.g., myocardial infarction, unstable angina) within 24 weeks prior to screening or any history of significant cerebrovascular disease; 3. Any of the following laboratory abnormalities at screening: white blood cell count <3.0×10⁹/L, neutrophil count <1.0×10⁹/L, lymphocyte count <0.5×10⁹/L, hemoglobin <90 g/L, platelet count <50×10⁹/L; severe hepatic impairment (ALT or AST ≥3 times ULN, total bilirubin ≥1.5 times ULN, excluding serum ALT or AST elevation due to dermatomyositis); severe renal impairment (creatinine clearance ≤45 mL/min); 4. Patients hospitalized for severe infection within 60 days prior to screening, or who received intravenous antibiotics (patients who used intravenous antibiotics must complete a five-half-life washout period and confirm absence of active infection before enrollment), but may receive empirical oral antibiotics or topical antibiotics; 5. Active tuberculosis infection that is untreated or inadequately treated; Latent tuberculosis infection (LTBI) requires at least 2 weeks of preventive antituberculosis therapy (including at least 2 antituberculosis drugs) prior to randomization, continuing through study completion. LTBI is defined as: Positive IGRA result (acceptable IGRA assays include: QFT-GIT, QFT-G, and T-spot® TB test); 6. Active viral hepatitis at screening: HBsAg-positive, HBeAg-positive, or HBV-DNA >10³ copies/L (HBV-DNA testing required if HBcAb-positive); HCVAb-positive; 7. Documented HIV infection, evidenced by positive serological test results or positive HIV serological test results at screening; 8. If the patient develops ILD-related clinical manifestations or progressive radiographic worsening within 4 weeks, RP-ILD should be considered. RP-ILD is defined as the presence of any one of the following four conditions within 1 month after the onset of respiratory symptoms: ① Acute and progressive worsening of dyspnea requiring hospitalization or supplemental oxygen; ② Decline in pulmonary function, manifested as a decrease in FVC% >10% with or without a decrease in DLco% >15%; ③ Increased interstitial abnormalities on chest HRCT scan >20%; ④ Decrease in arterial blood gas or partial pressure of oxygen >10 mmHg, indicating respiratory failure; and PaO₂/FiO₂≥200 mmHg.

Rituximab within 6 months prior to screening;

JAK inhibitors within 2 weeks prior to screening;

Use of other biologics (including but not limited to anakinra, adalimumab, infliximab) or other immunosuppressive agents (including but not limited to methotrexate, azathioprine, mycophenolate mofetil) within 4 weeks prior to screening; 15. Patients with prior use of the study drug, other IL-6 inhibitors, or analogues; 16. Pregnant or lactating women, or women planning to become pregnant or initiate lactation; 17. History of malignant tumors within the past 5 years (excluding adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cervical carcinoma in situ with no evidence of recurrence within the preceding 5 years); 18. Other conditions deemed ineligible for study inclusion by the investigator.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Tocilizumab

    Biological/Vaccine

    Tocilizumab is a humanized monoclonal antibody targeting the IL-6 receptor, exerting therapeutic effects by specifically blocking the IL-6 signaling pathway.

  • Standard medical treatment

    Drug

    Standard medical treatment for patients with anti-MDA5+ dermatomyositis

Treatment groups

110 Participants
are divided into 2 treatment groups
Group A: TCZExperimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

TIS improvement

Proportion of patients achieving minimal improvement in Total Improvement Score (TIS≥20)

Time frame
at Week 16 of treatment
2

ILD improvement

Change in PaO2/FiO2 ratio from baseline (patients with concomitant ILD)

Time frame
at Week 16

Secondary outcomes

Other outcomes

Sponsors and contacts

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