Baricitinib in the Treatment of New-onset Juvenile Dermatomyositis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 26
- 主要终点
- PRINTO 20 (Paediatric Rheumatology INternational Trials Organisation scale)
研究概览
简要总结
The MYOCIT study aims to evaluate the efficacy and safety of baricitinib in association with corticosteroids in new-onset patients with juvenile dermatomyositis (JDM) in a phase II trial with the objective to obtain a better efficacy than the conventional combination methotrexate (MTX) and corticosteroids over the 24 week study period. Thus, the investigators hypothesize that baricitinib could be used as a first line treatment in all forms of DMJ, including the most severe one, with a good safety profile.
详细描述
Juvenile dermatomyositis (JDM) is a rare and severe paediatric-onset idiopathic inflammatory myopathy, associated with significant morbidity and mortality. The combination of corticosteroids and methotrexate (MTX) is recommended in new-onset JDM according to one randomized trial. However, in this trial, treatment failures were reported in 13/46 (28%) patients and severe JDM, (cutaneous or gastrointestinal ulceration, interstitial pulmonary disease, cardiomyopathy) were not taken into account. These data emphasize the need for a more efficient first-line treatment. Considering: 1) the strong implication of type IFN-I in the pathophysiology of JDM 2) the report of the efficacy and safety of JAK inhibitors (JAKis) (baricitinb, tofacitinib) in about 50 refractory DM patients, and 9 JDM, a trial which evaluates the efficacy and safety of baricitinib in combination with corticosteroids in new-onset JDM is warranted.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 < 74 and/or CMAS < 45)
- •Seropositivity or vaccination for chickenpox
- •For patients of childbearing age (following menarche) : Negative βHCG and effective method of contraception (sexual abstinence, hormonal contraception, intrauterine device or hormone-releasing system, cap, diaphragm or sponge with spermicide, condom) until the 7 days after administration of the last dose of Baricitinib
- •Informed consent form signed by the patient or child' s parents Patient affiliated to a social security regime
排除标准
- •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 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 according to investigator appreciation, but necessarily, 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
- •History of thrombosis or considered at high risk of venous thrombosis by the investigator
- •Presence of severe JDM-related involvements: cardiovascular (requiring vasopressive drug and/or intensive care unit), respiratory (requiring oxygen and/or intensive care unit), gastrointestinal (requiring abdominal surgery).
- •History of severe non-related JDM involvement: 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.
- •Actual or in project of pregrancy and breast-feeding until the 7 days after administration of the last dose of Baricitinib
- •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
研究组 & 干预措施
Baricitinib
干预措施: Baricitinib (Drug)
Baricitinib
干预措施: pharmacokinetics study (Biological)
Baricitinib
干预措施: dosage of cytokines (Biological)
Baricitinib
干预措施: Parent version of the Child Health Questionnaire (CHQ) (Behavioral)
Baricitinib
干预措施: Childhood Health Assessment Questionnaire (Behavioral)
Baricitinib
干预措施: Pregnancy test (Biological)
Baricitinib
干预措施: transcriptomic analysis (Biological)
结局指标
主要结局
PRINTO 20 (Paediatric Rheumatology INternational Trials Organisation scale)
时间窗: At week 24
Achievement of the validated juvenile dermatomyositis PRINTO 20 level of improvement. 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) : 1. muscle strength, assessed with the Childhood Myositis Assessment Scale (CMAS), 2. physician's global assessment of the patient's disease activity (Physician's VAS) 3. global disease activity assessment through the Disease Activity Score (DAS) 4. functional ability through the Childhood Health Assessment Questionnaire (C-HAQ) 5. parent's global assessment of the child's overall wellbeing (Parent's VAS) 6. health-related quality of life, through the parent version of the Child Health Questionnaire (CHQ-Phs) A higher score is 100% and means a better outcome, a lower score is 0% and means a worse result.
次要结局
- Pharmacokinetics (PK) study with through concentration(At weeks 4, 8, 12, and 24)
- PRINTO 20 Paediatric Rheumatology INternational Trials Organisation scale - level 20(At week 4, 8, 12 and 16)
- Pharmacokinetics study(At weeks 4, 8, 12, and 24)
- dosage of cytokines(At inclusion, weeks 4 and 24)
- transcriptomic analysis(At inclusion, weeks 4 and 24)
- Biopsy(At inclusion, weeks 4 and 24)
- PRINTO 50 Paediatric Rheumatology INternational Trials Organisation scale - level 50(At week 4, 8, 12 and 16)
- PRINTO 70 Paediatric Rheumatology INternational Trials Organisation scale - level 70(At week 4, 8, 12 and 16)
- PRINTO 90 Paediatric Rheumatology INternational Trials Organisation scale - level 90(At week 4, 8, 12 and 16)
- Total Improvement Score (TIS)(At inclusion, weeks 4, 8, 12, 16 and 24)
- Clinically inactive disease(At weeks 4, 8, 12 and 24)
- Dose of corticosteroid(At week 24)
- Cutaneous Dermatomyositis Disease Area and Severity Index (CDSAI)(At inclusion, weeks 4, 8, 12, 16 and 24)
- Myositis Disease Activity Assessment VAS (MYOACT)(At inclusion, weeks 4, 8, 12, 16 and 24)
- interstitial lung disease(At inclusion and at week 24)
- Pharmacokinetics (PK) study with maximal concentration(At weeks 4, 8, 12, and 24)
- Pharmacokinetics (PK) study with area under the curve(At weeks 4, 8, 12, and 24)