Baricitinib in Patients With Relapsing or naïve Dermatomyositis

• Status: Not yet recruiting
• Trial end date: 2025-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Dermatomyositis (DM) is a rare and disabling condition with an important impairment of quality of life and possible life-threatening complications.

Treatment is based on high doses of corticosteroids but this exposes patients to adverse events (cardiovascular mortality, glucocorticoids-induced muscle and skin damages). Corticosteroids taper is associated with disease relapses. Although there is no evidence from the literature, clinical practice guidelines recommends the use of DMARDs such as methotrexate. However, response is not complete and these DMARDS take time to act.

The interferon type I (IFN-I) pathway is involved in the pathophysiology of DM. Janus kinase 1 and 2 transduces IFN-I signals. In addition, JAK2 inhibition enhances muscle repair and force generation.

JAK 1/2 inhibitors permitted to dramatically and rapidly improve relapsing DM patients (n=4, case series).

Our hypothesis is that Janus kinase 1 and 2 (JAK1/2) inhibitors (baricitinib) will permit to obtain dermatomyositis (DM) improvement with a steroid sparing effect as compared to usual care.

Our primary objective is to evaluate the efficacy of baricitinib (JAK1/2 inhibitor) to obtain prednisone-free moderate improvement (ACR/EULAR ≥ 40) of DM as compared to placebo in addition to usual care.

BIRD is a multicenter phase III double blind randomized placebo-controlled trial with two parallel arms (1:1). This is an add-on trial to usual care with rapid corticoid taper.

This is a multicenter trial in different medical departments in hospitals across France in different regions.

Out- and in patients will be recruited in hospital departments involved in management and diagnosis of DM: departments of dermatology, rheumatology and internal medicine.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Criteria

Inclusion Criteria:

• Adult subjects (≥ 18 years old) < 75 years old

• Dermatomyositis defined according to the 239th ENMC criteria

• Active disease (ACR/EULAR criteria) defined as :

• Manual Muscle Testing (MMT-8) <145/150 and at least two additional abnormal corset measurements (CSM): >3/10 cm on Visual Analogue Scale (VAS) of patient global, physician global and extra-muscular disease activity, Health Assessment Questionnaire Disability Index >0.25, or elevated muscle enzymes.

• Or cutaneous CDASI > 20 and at least two additional abnormal corset measurements (CSM): >3/10 cm on Visual Analogue Scale (VAS) of patient global, physician global and extra-muscular disease activity, Health Assessment Questionnaire Disability Index >0.25, or elevated muscle enzymes

• for relapsing DM patients :

• in case of corticosteroid exposure patient must receive a stable dose < 30 mg/d prednisone with or without additional immunosuppressive therapy for at least 4 weeks before the baseline visit.

• Stable dose of immunosuppressive therapy for at least 3 months before

• Affiliation to a social security regime

• Written informed consent

Exclusion Criteria:

• Life-threatening complications :

• Severe swallowing troubles defined as: food swallowed the wrong way and/or time to drink a glass of 200 ml water above 30 seconds

• Interstitial lung disease related to the DM with one among the following complications (complications must be related to the ILD): dyspnea NYHA III, hypoxemia with PaO2≤65 mmHg, and/or DLCOc/Alveolar Volume ≤70% (pulmonary function test)

• Symptomatic myocarditis o Loss of walking ability

• Deep vein thrombosis/pulmonary embolism in past medical history in absence of anticoagulant

• Pregnant or lactating, or women planning to become pregnant or initiating breastfeeding

• No effective contraception during the study and one week after for women of childbearing age

• Renal impairment defined as clearance < 60 ml

• Strong Organic Anion Transporter 3 (OAT3) inhibitors

• A new cancer or malignancy except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured by the investigator

• Active severe infection including active hepatitis

• Evidence of latent tuberculosis (as documented by a positive QuantiFERON-TB Gold plus test)

• Absolute Neutrophil Count < 1x109 cells/L

• Haemoglobin (Hb) < 8 g/dL

• Liver insufficiency (Prothrombin time <60%)

• Previous treatment exposure relating to the treatment/procedures : • Rituximab treatment within 6months before inclusion

• IVIg, or cyclophosphamide infusion within the month before inclusion

• both methotrexate (0.3 mg/kg/w) and azathioprine exposure for at least 3 months each and at the 0.3 mg/kg/w and 2-3 mg/kg/d dosages respectively. (but exposure to either of these two drugs alone is not an exclusionary criterion)

• more than 2 weeks treatment duration with corticosteroids at the dose of 1 mg/kg/d before the inclusion.

• Hypersensitivity to the active substance (baricitinib) or to any of the excipients

• Conditions affecting the outcomes (Expected poor compliance)

• Severe disease damages: e.g. muscle weakness mainly related to muscle damage such as fat replacement of muscle) defined as persistent changes in anatomy, physiology, pathology or function which result from previously active disease and from complications of therapy or other events (e.g.; muscle atrophy, fatty replacement; skin skars, poilkilodermy). Severe disease damage is considered when the patient condition has no or minor ability to improve with the treatment.

• Significant uncontrolled cardiovascular, cerebrovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neuropsychiatric disorders, or abnormal laboratory values that developed during a qualifying study that, in the opinion of the investigator, poses an unacceptable risk for the patient's participation

• Chest imaging (CT scan or radiograph) showing abnormalities not related with the DM in the last 12 weeks judged by the investigator as clinically significant.

• Diagnosis of Covid 19 infection (SARSCoV-2 positive PCR)

• Participants included in other intervention research involving humans

• Patient under tutorship or guardianship, and incapable to give informed consent