Baricitinib in Juvenile Dermatomyositis (BAR-JDM): A multi-centre, open label, randomised, controlled, superiority, Bayesian, phase 3a trial comparing baricitinib and glucocorticoids to methotrexate and glucocorticoids over 52 weeks
Juvenile dermatomyositis (JDM)
a. Trial arms: i. Experimental arm: Baricitinib and glucocorticoids i. Control arm: Methotrexate and glucocorticoids (standard of care) b. Baricitinib: i. Dose range: Minimum 2mg to maximum 10mg. All participants on the baricitinib arm will start on a “lower” dose (2mg or 4mg) which is dependent upon their weight at the Baseline and Randomisation visit. At Week 12 and Week 24, if participants are clinically worsening or showing inadequate improvement, the baricitinib dose will be increased to a “higher” dose (6mg, 8mg, or 10 mg), dependent upon their estimated glomerular filtration rate and weight at that visit. ii. Dose frequency: Tablets to be taken once a day for first 12 weeks, then either twice a day or four times a day dependent upon dose for remainder of duration of treatment. iii. Route of administration: Oral (if children cannot swallow whole tablets, soluble form in water is acceptable). iv. Duration of treatment: 52 weeks (+/- 2 week protocol window). c. Methotrexate: i. Dose range: 15 mg/m2. Body weight, height, and body surface area will be assessed at every visit and used to determine methotrexate dosing and dispensing. ii. Dose frequency: Injection to be taken once weekly for duration of treatment. iii. Route of administration: Subcutaneous injection. iv. Duration of treatment: 52 weeks (+/- 2 week protocol window). d. Glucocorticoids (prednisolone): i. Dose range: All participants will receive the same protocolised oral prednisolone dosing regimen (and recommended non-mandatory supportive measures) starting from 2 mg/kg/day at the Baseline and Randomisation visit reducing to 0 mg/kg/day from Week 25. The Baseline and Randomisation body weight will be used to determine the glucocorticoid doses (prednisolone and methylprednisolone) for the duration of the trial. Maximum daily dose of oral prednisolone is 60 mg. ii. Dose frequency: Tablets to be taken once a day. iii. Route of administration: Oral (if children cannot swallow whole tablets, so
1. Patients with newly diagnosed (treatment naïve) juvenile dermatomyositis (JDM) who meet European League Against Rheumatism (EULAR)/ American College of Rheumatology (ACR) classification criteria for possible, probable or definite JDM; or modified (i.e. incorporating MRI muscle findings in place of EMG) Peter and Bohan criteria for possible, probable or definite JDM. 2. Active disease for JDM using the following pre-specified definition: a. Active inflammatory disease based on persisting or worsening muscle weakness (for example, Manual Muscle Testing 8 (MMT8) <78/80 or CMAS <49/52), and b. At least one other sign of active disease: i. Elevated serum levels of at least one muscle enzyme (creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT)) above upper limit of normal and being explained by muscle involvement and no other cause such as liver disease, or ii. Inflammation in recent (<12 weeks) muscle biopsy or MRI scan, or iii. Active extra muscular disease: dermatomyositis-specific skin rash, arthritis, or interstitial lung disease (ILD) as suggested by chest x-ray or high-resolution computerised tomography (HRCT) or pulmonary function test. 3. Participants aged ≥2 years to <17 years at the Baseline and Randomisation visit. 4. Written informed consent from: a. Participants who have reached the age of consent (16 years), or b. Parent/legal representative of participants who have not reached the age of consent (16 years); and assent, where possible, from the participant.
1. Participants with other types of inflammatory myopathies. 2. Participants where the use of baricitinib, methotrexate or glucocorticoids would be contraindicated, including known hypersensitivity or history of severe allergic reaction to any of the study medications or their excipients. 3. Participants who are pregnant or breastfeeding at the screening visit. 4. Participants of childbearing potential that are unwilling to have pregnancy testing done according to the protocol schedule for the duration on the trial. 5. Participants of childbearing potential or fertile men that are either considering becoming pregnant/having children or are unable/unwilling to use an acceptable method of contraception to avoid pregnancy for the duration on the trial and for 6 months after the last dose of trial medication. 6. Participants who have an active varicella zoster infection (chickenpox) or have had exposure to a case of varicella (chickenpox or shingles) within 21 days of the screening visit. 7. Participants who have active herpes zoster that resolved within 8 weeks of the screening visit. 8. Participants who have a serious systemic or local infection or who have had a serious systemic or local infection within 12 weeks of the screening visit. 9. Participants who have received live/attenuated vaccines in the 4 weeks prior to screening or who plan to receive live/attenuated vaccines for the duration on the trial. 10. Participants with a history of active hepatitis B, hepatitis C or human immunodeficiency virus. 11. Participants with evidence of active or latent tuberculosis. 12. Participants with any of the following laboratory values at screening: a. Haemoglobin (Hb) <80 g/L (alternative units <8 g/dL), or b. Absolute lymphocyte count (ALC) <0.5x109/L (alternative units <500 cells/mm³), or c. Absolute neutrophil count (ANC) <1x109/L (alternative units 1000 cells/mm³), or d. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m². 13. Any other clinical feature or labo