Baricitinib in patients with relapsing or naïve dermatomyositis.Multicenter trial, double blind randomized controlled trial with 2 parallel groups. This is an add-on trial with intention to treat analysis. MedDRA version: 20.0 Level: LLT Classification code 10001403 Term: Adult dermatomyositis System Organ Class: 100000004858
Conditions
Interventions
Trade Name: OLUMIANT 4mg
Product Name: Baricitinib
Pharmaceutical Form: Tablet
INN or Proposed INN: BARICITINIB
CAS Number: 1187594-09-7
Concentration unit: mg milligram(s)
Concentration type: equal
C
Sponsors
Assistance Publique-Hopitaux de Paris
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Adult subjects (= 18 years old) 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 o in case of corticosteroid exposure patient must receive a stable dose =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Life-threatening complications o Severe swallowing troubles defined as: food swallowed the wrong way and/or time to drink a glass of 200 ml water above 30 seconds o 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) o Symptomatic myocarditis o Loss of walking ability - Deep vein thrombosis/pulmonary embolism in past medical history in absence of anticoagulant - Ongoing or planned pregnancy - 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 - Synchronous malignancy - Active severe infection including active tuberculosis and active hepatitis - 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: eg. 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. -Participants included in other intervention research involving humans - Patient under tutorship or guardianship, and incapable to give informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: evaluate the efficacy of baricitinib (JAK1/2 inhibitor) to obtain prednisone-free DM moderate improvement as compared to placebo, in addition to usual care. ;Secondary Objective: to compare between the two groups (baricitinib + usual care versus placebo+ usual care):the proportion of patients with: minimal improvement (>20 points total improvement ACR/EULAR), moderate improvement (ACR/EULAR40), major improvement at W5, W12 ,W24.The rate of prednisone-free moderate improvement in different subgroups: i) naive vs relapsing DM patients ii) patients with severe vs no or mild muscle involvement .The skin effect using a specific scale developed for DM assessing both skin activity and skin damages (Cutaneous Dermatomyositis Disease Area and Severity Index at W5, W12, W24.The cumulative incidence of relapse and the time to first relapse.The cumulative dose of corticosteroids.The 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/day, of more than 4.0 mg to not more than 7.5 mg/day, and of more than 7.5 mg/day. during weeks 20 through 24.The safety;Primary end point(s): The primary endpoint is a moderate improvement at 24 weeks without prednisone: prednisone-free moderate improvement. The moderate improvement is defined as a total improvement score superior to 40 following ACR/EULAR definition(58). A major improvement (>60 improvement score ACR/EULAR), is observed only in a minority of patients (<20%; personal data from our center, MASC project) and is not a realistic objective. The ACR/EULAR improvement score (0–100) is determined by summing scores of the six score set measures (CSM): -physician global activity (visual analogue scale 0-10 cm) -patient global activity (visual analogue scale 0-10 cm) -muscle enzymes -manual muscle testing 8 score (0-150) -health assessment questionnaire -extra-muscular assessment (Visual Analogues Scales of 6 extra-muscular domains including the skin) The i | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. DM improvement at 5, 12 and 24 weeks in terms of: - minimal improvement (>20 points total improvement ACR/EULAR), - moderate improvement (>40 points total improvement ACR/EULAR) - major improvement (>60 points total improvement ACR/EULAR) 2. Primary endpoint (prednisone-free moderate improvement at W24) in the following subgroups: - DM naive patients at baseline vs others - DM with a severe muscle weakness (MMT8 baseline <125/150) vs others 3. Cutaneous disease activity and damage evaluated using the CDASI - Activity and CDASI damages at 5, 12 and 24 weeks 4. Cumulative incidence of relapse and the time to first relapse 5. Cumulative dose of corticosteroids 6. 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. 7. Safety including the incidence, nature, and severity of adverse events and serious adverse events and laboratory abnormalities. ;Timepoint(s) of evaluation of this end point: 5,12,24 weeks | — |
Countries
France
Contacts
Public Contactfatiha ACED-DJENNAOUI
Assistance Publique-Hopitaux de Paris
Outcome results
None listed