New-onset juvenile dermatomyositis MedDRA version: 20.0 Level: LLT Classification code 10008521 Term: Childhood dermatomyositis System Organ Class: 100000004858
Conditions
Interventions
Trade Name: OLUMIANT® 2 mg comprimés pélliculés
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Baricitinib
Other descriptive name: Baricitinib
Concentration unit: mg milligram(s)
Concentratio
Sponsors
Assistance Publique des Hôpitaux de Paris
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patient aged 3-18 years with new-onset juvenile dermatomyositis, according to the ENMC 2018 dermatomyositis classification criteria - Muscle weakness at MMT and/or CMAS (MMT =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Amyopathic dermatomyositis (without muscle weakness) - Inability to be treated by oral way or to take pills - Previous treatment with JAK inhibitor - Previous treatment of JDM with immunosuppressive drugs or biologics other than corticosteroids. Previous treatment with prednisone was allowed if the daily dose was greater than 1 mg/kg for no more than 1 month. - Previous history of cancer - Live vaccine within the 4 weeks before starting baricitinib therapy - Current, or recent (< 4 weeks prior to baseline) of active infections, including HBV, HCV, HIV, tuberculosis, - Positive blood CMV PCR - Creatinine clearance < 40 ml/min - Lymphocytes < 0,5x109 cell/L and Neutrophils < 1x109 cell/L - Hemoglobin < 8 g/dL - Symptomatic herpes herpes simplex infection within 12 weeks prior to inclusion - Positivity for antiphospholipids antibodies (Lupus anticoagulant and/or anti-beta2 glycoprotein 1 and/or anti-cardiolipin) - History of thrombosis or considered at high risk of venous thrombosis by the investigator - History or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological or neuropsychiatric disorders or any other serious and/or instable illness that, in the opinion of the investigator, could constitute an unacceptable risk, when taking baricitinib. In particular JDM-related-acute severe respiratory distress requiring oxygen is an exclusion criteria - Breast-feeding, pregnancy - Patient on AME (state medical aid) - Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of baricitinib in patients with a new-onset JDM at week 24 according to PRINTO 20 level of improvement ;Secondary Objective: To assess the efficacy of baricitinib : - according to PRINTO 20, 50, 70, and 90 levels of improvement and to the criteria of clinically inactive disease - on global disease activity of various extramuscular organ systems according to the MYOACT - on interstitial lung disease - on JDM-related-skin disease according to the cutaneous DM disease area and severity index To determine the response rate to baricitinib by the TIS using the 2016 ACR/EULAR myositis response criteria To assess the safety of baracitinib, the reduction in oral corticosteroids, a correlation between the muscle biopsy score and the response to baricitinib, and between PK and response to baricitinib To assess the following measures in order to identify biomarkers of JDM activity and predictive of the response to baricitinib at W24: o cytokine circulating levels independently or jointly at V0 o genes expression within 800 genes related to immunity analyzed at V0 To characterize the PK of baricitinib ;Primary end point(s): PRINTO 20 level of improvement is defined as a 20% or greater improvement in three or more of the six variables of the juvenile dermatomyositis core set, with one or no variable worsening by more than 30% (muscle strength can not be the variable worsening) : - muscle strength, assessed with the Childhood Myositis Assessment Scale (CMAS), with 0 the worst score and 52 the best; - physician’s global assessment of the patient’s disease activity on a 0–10 cm visual analogue scale (Physician’s VAS), with 0 the best score and 10 the worst; - global disease activity assessment through the Disease Activity Score (DAS), with 0 the best score and 20 the worst; - functional ability through the Childhood Health Assessment Questionnaire (C-HAQ), with 0 the best score and 3 the worst; - parent’s global assessment of the child’ | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) The achievement of the PRINTO 20 levels of improvement 2) The achievement of the PRINTO 50, 70 and 90 levels of improvement 3) Relative and absolute variations of TIS 4) Clinically inactive disease according to the PRINTO criteria 5) Relative and absolute variations of CDSAI 6) Relative and absolute variations of MYOACT 7) Improvement of interstitial lung disease if present at screening: Improvement of pulmonary function tests (improvement of at least 10% of FCV, PTC, and DLCO) and/or improvement of Lung tomodensitomery scored according to a specific scale 8) Dose of corticosteroids at week 24 9) Non-compartmental analysis of baricitinib PK 10)Correlation between PK of baricitinib and disease activity ‘s scores 11) Measurement of serum IFN - a, IFN-?, IL-1ß, IL-4, Il-5, IL-6, IL-8, IL-10, IL-12p70, IL-22, TNF a 12) Study of genes expression within 800 genes related to immunity 13) Assessment of muscle biopsies according to the internationally validated score system (Dr Gitiaux);Timepoint(s) of evaluation of this end point: 1) at weeks 4, 8, 12, 16 2) at weeks 4, 8, 12, 16, 24 3) between inclusion and weeks 4, 8, 12, 16, 24 4) at weeks 4, 8, 12, 24 5) between inclusion and weeks 4, 8, 12, 16, 24 6) between inclusion and weeks 4, 8, 12, 16, 24 7) at screening 8) at week 24 11)at inclusion, weeks 4 and 24. 12) at inclusion, weeks 4 and 24. | — |
Countries
France
Contacts
Public ContactDRCI, Hôpital St Louis
Assistance Publique des Hôpitaux de Paris
Outcome results
None listed