Juvenile dermatomyositis (JDM) Musculoskeletal Diseases
Conditions
Interventions
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.
Sponsors
University College London
Eligibility
Sex/Gender
All
Age
2 Years to 17 Years
Inclusion criteria
Inclusion criteria: 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.
Exclusion criteria
Exclusion criteria: 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) 3 g of intravenous methylprednisolone within 4 weeks prior to randomisation. 16. Participants who have received oral prednisolone/prednisone at a dose =2 mg/kg once daily for more than 4 weeks and completing the course in the 4 weeks prior to randomisation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is the proportion of participants achieving clinically inactive disease, as per modified PRINTO criteria, at Week 52 AND off glucocorticoids from Week 40. Clinically inactive disease as per modified PRINTO criteria is achieved if a participant fulfils the following criteria: a.No active skin disease, and b.Physician global assessment (PhyGLOVAS) =0.2/10 on a visual analogue scale, and c.Two of the following three criteria: i.Creatine kinase (CK) =150 U/L. ii.Childhood Myositis Assessment Scale (CMAS) =48/52. iii.Manual Muscle Testing 8 (MMT8) =78/80. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Proportion of participants requiring protocoled baricitinib dose escalation at Week 12 or Week 24. 2. Proportion of participants achieving clinically inactive disease and off glucocorticoids from Week 25. 3. Proportion of participants achieving clinically inactive disease at Week 52 but received prednisolone beyond Week 25. 4. Proportion of participants requiring rescue treatment. 5. Cumulative dose of prednisolone (mg/kg) at trial end. 6. Cumulative dose of methylprednisolone (mg/kg) at trial end. 7. Time to clinically inactive disease (see Appendix 1 of protocol for definition) following the protocoled glucocorticoid tapering schedule. 8. Number of grade 3 to 5 adverse events (AEs), including deaths, and serious adverse events (SAEs) reported. 9. Toxicity of glucocorticoids as assessed by the paediatric glucocorticoid toxicity index. 10. Proportion of patients with disease flares defined as worsening disease after clinically inactive disease as assessed at the time of trial visits within 52 weeks. 11. Cumulative weight adjusted dose of prednisolone or methylprednisolone received. 12. Duration of glucocorticoid treatment from the Baseline and Randomisation visit. 13. JDM Paediatric Rheumatology International Trials Organisation (PRINTO) 20, 50, 70, and 90 levels of improvement (20%, 50%, 70%, and 90% improvement from the Baseline and Randomisation visit in three of six core set variables at a given visit with one or no variable worsening by more than 30% (muscle strength excluded)) at Weeks 12, 24, 39 and 52, with adherence to glucocorticoid schedule. 14. Minimal clinical response according to the International Myositis Assessment and Clinical Studies (IMACS) Group criteria at Weeks 12, 24, 39 and 52, with adherence to glucocorticoid schedule (Web calculator for 2016 ACR/EULAR Criteria for Minimal, Moderate, and Major Clinical Response in Juvenile Dermatomyositis (nih.gov)). 15. Total improvement score at Week 12, 24, 39 and 52, with adherence to glucocorticoid | — |
Countries
England, Scotland, United Kingdom
Contacts
Public ContactRachel McComish
Outcome results
None listed