ANAkinra in Severe Juvenile Idiopathic Arthritis of Systemic Onset (ANAJIS)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 6
- 主要终点
- Improvement of systemic symptoms between day 1 and month 1 as assessed by the resolution of the fever if present initially, by a 50% decrease or a normalization of the C-reactive protein and of the first hour ES
研究概览
简要总结
- Main objective: To test the efficacy of anakinra treatment in children or young adults with corticosteroid-resistant or -dependent Systemic-Onset Juvenile Idiopathic Arthritis (SO-JIA)
- Design: Double blind, randomized trial testing the efficacy of one month Anakinra treatment versus placebo (2 groups of 12 patients each). All the patients will be treated with anakinra during the following 11 months and the dose of corticosteroids will be gradually tapered (= descriptive part of the trial to assess the tolerance and efficacy over 12 months).
- Hypothesis: 70% significant improvement after 1 month in Anakinra-treated patients versus no more than 10% in the placebo group.
- Main inclusion criteria : diagnosis of SO-JIA (Durban consensus conference criteria), age: 2 to 20 years at inclusion, active, corticosteroid-resistant or -dependent disease, no previous IL-1ra treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 2 Years 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •SO-JIA (Edmonton's revision of Durban's consensus conference criteria)
- •Age: at least 2 years and less than 20 years at treatment initiation
- •Disease duration of at least 6 months
- •Failure of corticosteroid treatment or requirement for corticosteroid treatment at a daily dose equal to or over 0.3 mg/kg (10 mg in patients whose weight is over 34 kg)
- •Active and severe systemic symptoms and/or arthritis as assessed by an experienced pediatric Rheumatologists, with at least 3 of the following criteria when assessing Giannini's core-set items: 1) physician global assessment of disease activity of at least 20/100; 2) parent/patient assessment of disease effect on overall well-being of at least 20/100; 3) functional disability with a Children Health Assessment Questionnaire (CHAQ, Ref [9]) score equal to or higher than 0.375/3; 4) 2 joints or more with active arthritis 5) 2 joints or more with non-irreversible limited range of motion (irreversible limited range of motion will be defined by radiological evidence of irreversible joint damage and ankylosis) 6) erythrocyte sedimentation rate (ESR) equal to or higher than
- •In the absence of disease-related fever, either CRP or first hour ESR or both have to be over the upper limit of normal values so that treatment effect on the systemic part of the disease can be objectively evaluated.
- •Patients with polyarthritis (at least 5 joints with inflammation and/or limitation of motion) will be eligible for this study only if at least 50% of the affected joints do not present radiological evidence of irreversible damage.
- •Informed consent signed by the parents or the person legally responsible for the patient if the patient is less than 18, and by the patient if old enough
- •Teenager girls or young women with childbearing potential must use a contraceptive method (including abstinence
- •tuberculin test performed before Day 1 and must either be negative or positivity must be related to previous immunization and of normal intensity according to the investigator's judgment
排除标准
- •Previous treatment with IL-1Ra
- •intra-articular injection or change in the doses of non-steroidal anti-inflammatory drugs and corticosteroids in the 4 weeks preceding the initiation of anakinra treatment
- •Treatment with another immunosuppressive or disease-modifying drugs that could not be stopped before inclusion (for a duration depending on the drug pharmacokinetic properties)
- •Contra-indication to the use of anakinra including ongoing active infection or allergy to E Coli's derivate or other components of the drug
- •Previous history of malignancy or heart insufficiency
- •Patients with asthma require to be previously assessed by a pneumonologist
- •Obvious need of therapeutic intervention before study completion such as surgery, intra-articular injection, life vaccine administration
- •Any of the following: leucocyte counts < 3.6 x 10e9/L, polymorphonuclear neutrophil counts < 1.5 x 10e9/L, platelets < 150 000/mm3, serum creatinin > 1.5 the upper limit of normal range for age, serum alanine and aspartate transaminases > 2 times the upper limit of the normal range, serum bilirubin > 2 times the upper limit of the normal range
研究组 & 干预措施
Teatment with ANAKINRA (2 mg/kg SC daily, maximum 100 mg)
Anakinra is injected subcutaneously once a day , for a dosage of 2 mg/kg per day with a maximum of 100 mg per day. The dose should be administered at approximately the same time every day. The treatment should be administered with no interruption during the whole study period.
干预措施: Anakinra (Drug)
Placebo treatment
Placebo is injected subcutaneously once a day using the same volume as the anakina treatment (dosage of 2 mg/kg per day of anakinra with a maximum of 100 mg per day). The dose should be administered at approximately the same time every day. The placebo treatment should be administered with no interruption during the whole study period.
干预措施: Pneumo23 (Biological)
Teatment with ANAKINRA (2 mg/kg SC daily, maximum 100 mg)
Anakinra is injected subcutaneously once a day , for a dosage of 2 mg/kg per day with a maximum of 100 mg per day. The dose should be administered at approximately the same time every day. The treatment should be administered with no interruption during the whole study period.
干预措施: Pneumo23 (Biological)
Placebo treatment
Placebo is injected subcutaneously once a day using the same volume as the anakina treatment (dosage of 2 mg/kg per day of anakinra with a maximum of 100 mg per day). The dose should be administered at approximately the same time every day. The placebo treatment should be administered with no interruption during the whole study period.
干预措施: Placebo (Other)
结局指标
主要结局
Improvement of systemic symptoms between day 1 and month 1 as assessed by the resolution of the fever if present initially, by a 50% decrease or a normalization of the C-reactive protein and of the first hour ES
时间窗: Day 1, 1 Month
Number of joints with limitation of motion
时间窗: Day 1, 1 Month
Physician assessment of disease activity
时间窗: Day 1, 1 Month
Parent or patient's assessment of disease activity
时间窗: Day 1, 1 Month
Childhood health assessment questionnaire
时间窗: Day 1, 1 Month
30% improvement of JIA activity after 1 month compared to day 1 according to Giannini's core-set criteria, ie 30% improvement of at least 3 of the 6 items and no more than one item worsened by 30% or more.
时间窗: Day 1, 1 Month
Number of active arthritis
时间窗: Day 1, 1 Month
First hour ESR)
时间窗: First hour
次要结局
- Proportion of patients reaching 50%, 70% and 100% improvement of JIA activity according to Giannini's core-set criteria at each visit (day 15, month 1 to 6, month 9 and month 12)(Day 15, Month 1 to 6, Month 9 and Month 12)
- Number, severity and type of adverse events over 12 months(Over 12 Months)
- Proportion of patients in whom the daily dose of corticosteroids can be reduced to less than 0.3 mg/kg (less than 10 mg in patients over 34 kg) at month 6(Month 6)
- Proportion of patients with a normalization of the glycosylated ferritin / ferritin ratio (if lower than 1/4 initially) after 1, 2 and 6 months(1 Month, Month 2, Month 6)
- Variation of cytokine expression by PBMC between Day 1 and Month 1 and Month 6(Day 1, Month 1, Month 6)
- Antibody response at month 1 and month 6 to Pneumo 23® immunization: immunization on day 1 against Streptococcus pneumoniae(Month 1, Month 6)
- Pharmacokinetic study at month 2 and month 6(Month 2, Month 6)