Baricitinib for Dermatomyositis

Inclusion criteria

• {"criterion_text":"- Adult subjects (≥ 18 years old) < 65 years old"}
• {"criterion_text":"- Dermatomyositis (DM) defined according to the 239th ENMC criteria: either naïve or non-naïve DM"}
• {"criterion_text":"- Active disease (ACR/EULAR criteria) defined as: •\tManual 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. •\tOr 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"}
• {"criterion_text":"-\tfor relapsing/non naïve DM patients o\tin 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. o\tStable dose of immunosuppressive therapy for at least 3 months before"}
• {"criterion_text":"- Affiliation to a social security regime"}
• {"criterion_text":"- Written informed consent"}

Exclusion criteria

• {"criterion_text":"- Life-threatening complications o\tSevere swallowing troubles defined as: food swallowed the wrong way and/or time to drink a glass of 200 ml water above 30 seconds related to DM o\tInterstitial 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) o\tSymptomatic myocarditis o\tLoss of walking ability"}
• {"criterion_text":"- Contraindication to Methotrexate and/or Azathioprine including hypersensitivity to the active substances or to any of the excipients"}
• {"criterion_text":"- Conditions affecting the outcomes (Expected poor compliance)"}
• {"criterion_text":"- Patient with deep vein thrombosis/pulmonary embolism or antecedent"}
• {"criterion_text":"- 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 scars, poikiloderma). Severe disease damage is considered when the patient condition has no or minor ability to improve with the treatment."}
• {"criterion_text":"-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"}
• {"criterion_text":"- 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.-Participants included in other intervention research involving humans"}
• {"criterion_text":"- Patient under tutorship or guardianship, and incapable to give informed consent"}
• {"criterion_text":"- Patient with antecedent of cardiovascular event (myocardial infarction or ischemic stroke)"}
• {"criterion_text":"- Patient who is current or past long-time smoker"}
• {"criterion_text":"- Pregnant or lactating, or women planning to become pregnant or initiating breastfeeding"}
• {"criterion_text":"-Active severe infection including active hepatitis"}
• {"criterion_text":"- No effective contraception during the study and one week after for women of childbearing age"}
• {"criterion_text":"- Renal impairment defined as clearance < 60 ml"}
• {"criterion_text":"- Strong Organic Anion Transporter 3 (OAT3) inhibitors"}
• {"criterion_text":"- Active cancer or history of malignancy"}
• {"criterion_text":"-Participants included in other intervention research involving humans"}
• {"criterion_text":"- Evidence of latent tuberculosis (as documented by a positive QuantiFERON-TB Gold plus test)"}
• {"criterion_text":"- Absolute Neutrophil Count < 1x109 cells/L"}
• {"criterion_text":"- Haemoglobin (Hb) < 8 g/dL"}
• {"criterion_text":"- Severe hepatic impairment attested by FV (coagulation factor)<30%"}
• {"criterion_text":"- Liver insufficiency (Prothrombin time <60%)"}
• {"criterion_text":"- Previous treatment exposure defined as follows: •\tRituximab treatment within 6 months before inclusion •\tIVIg, or cyclophosphamide infusion within the month before inclusion •\t•\tboth 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 with failure of both (but exposure and/or failure to either of these two drugs alone is not an exclusion criterion) •\tfor naïve DM patients only more than 2 weeks treatment duration with corticosteroids at the dose of 1 mg/kg/d before the inclusion."}
• {"criterion_text":"- Hypersensitivity to the active substance (baricitinib) or to any of the excipients"}

Primary endpoints

• {"endpoint_text":"-Primary endpoint: moderate improvement (defined as a total improvement score superior or equal to 40 following ACR/EULAR definition) without corticosteroids at week 24 (prednisone-free moderate improvement).","definition_or_measurement_approach":"Moderate improvement defined as total improvement score ≥ 40 following ACR/EULAR definition; assessed at week 24 as prednisone-free moderate improvement (no corticosteroids at week 24)."}

Secondary endpoints

• {"endpoint_text":"-DM improvement at 5, 12 and 24 weeks in terms of: •\tminimal improvement (≥20 points total improvement ACR/EULAR), •\tmoderate improvement (≥40 points total improvement ACR/EULAR) •\tmajor improvement (≥60 points total improvement ACR/EULAR)","definition_or_measurement_approach":"Proportion of patients achieving minimal (≥20), moderate (≥40) and major (≥60) total improvement ACR/EULAR at weeks 5, 12 and 24."}
• {"endpoint_text":"-Primary endpoint (prednisone-free moderate improvement at W24) in the following subgroups: •\tDM naive patients at baseline vs others •\tDM with a severe muscle weakness (MMT8 baseline <125/150) vs others","definition_or_measurement_approach":"Subgroup analyses of the primary endpoint (prednisone-free moderate improvement at week 24) comparing DM-naïve vs non-naïve and MMT8 <125/150 vs others."}
• {"endpoint_text":"-Cutaneous disease activity and damage evaluated using the CDASI - Activity and CDASI damages at 5, 12 and 24 weeks","definition_or_measurement_approach":"Cutaneous disease activity and damage measured by CDASI Activity and CDASI Damage scores at weeks 5, 12 and 24."}
• {"endpoint_text":"-Cumulative incidence of relapse and the time to first relapse","definition_or_measurement_approach":"Cumulative incidence of relapse and time-to-first-relapse analysis over study follow-up (assessed per protocol)."}
• {"endpoint_text":"-Cumulative dose of corticosteroids","definition_or_measurement_approach":"Total cumulative corticosteroid dose received by participants during the study period."}
• {"endpoint_text":"-Proportions of participants with an average prednisone dose of 0 mg per day, of more than 0 mg to not more than 4.0 mg per day, of more than 4.0 mg to not more than 7.5 mg per day, and of more than 7.5 mg per day during weeks 20 through 24.","definition_or_measurement_approach":"Proportion of participants in predefined average prednisone dose categories (0, >0–4.0 mg/d, >4.0–7.5 mg/d, >7.5 mg/d) during weeks 20–24."}
• {"endpoint_text":"-Safety including the incidence, nature, and severity of adverse events and serious adverse events and laboratory abnormalities.","definition_or_measurement_approach":"Safety assessed by incidence, nature and severity of AEs and SAEs and laboratory abnormalities throughout the study."}

Methods

• Recruitment of out-patients and in-patients through participating hospital departments managing dermatomyositis (dermatology, rheumatology, internal medicine) across France (sites listed in protocol). No digital, remote or registry-based recruitment methods are specified in the public summary.

France

Earliest CTIS Part Ii Submission Date

20-08-2024

Latest Decision Or Authorization Date

19-09-2025

Processing Time Days

395

Number Of Sites

21

Number Of Participants

62

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France