A Randomized, Double-blind, Placebo Controlled, Withdrawal Study of Flare Prevention of Canakinumab (ACZ885) in Patients With Systemic Juvenile Idiopathic Arthritis (SJIA) and Active Systemic Manifestations
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 177
- 试验地点
- 14
- 主要终点
- Part I: Percentage of Patients Who Were on Steroids at Entry Into Part I and Who Were Able to Taper Steroid as Per Protocol in at Least 25% of the Patients Who Entered the Study Taking a Steroid
研究概览
简要总结
This two-part study assessed the sustained efficacy of canakinumab in the double-blind Part II and the ability to taper steroids in the open label Part I.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 2 Years 至 19 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of systemic juvenile idiopathic arthritis as per International League Against Rheumatism (ILAR) definition that must have occurred at least 2 months prior to enrollment with onset of disease < 16 years of age.
- •Arthritis in one or more joints with or preceded by fever of at least 2 weeks duration that is documented to be daily for at least 3 days with accompanying symptoms
- •Active disease at the time of enrollment defined as follows:
- •At least 2 joints with active arthritis (using American College of rheumatology) ACR definition of active joint)
- •Documented spiking, intermittent fever (body temperature > 38oC) for at least 1 day during the screening period within 1 week before first study drug dose
- •C-reactive protein > 30 mg/L (normal range < 10 mg/L)
- •No concomitant use of second line agents such as disease-modifying and/ or immunosuppressive drugs will be allowed with the exception of:
- •Stable dose of methotrexate for at least 8 weeks prior to the screening visit, and/or folic/folinic acid per standard medical practice
- •Stable dose of no more than one non-steroidal anti-inflammatory drug for at least 2 weeks prior to the screening visit
- •Stable dose of steroid treatment < or = to 1.0 mg/kg/day in 1-2 doses per day of oral prednisone or equivalent
- •Exclusion criteria:
- •Diagnosis of active macrophage-activation syndrome (MAS) within the last 6 months
- •Risk factors for tuberculosis
- •Patients with active or recurrent bacterial, fungal or viral infection at the time of enrollment, including patients with evidence of HIV infection, Hepatitis B and Hepatitis C infection
- •Other protocol inclusion/exclusion criteria may apply
排除标准
- 未提供
研究组 & 干预措施
Canakinumab
In Part I participants received open label 4 mg/kg canakinumab subcutaneous injection every 4 weeks for up to 32 weeks. For the first 8 weeks Part Ia (4 weeks) and Ib (4 weeks) patients maintained a stable oral steroid dose (prednisone or equivalent) followed by Ic an up to 20 week steroid tapering period and then Id a 4 week stable steroid dose period. Participants were then randomized to receive either 4 mg/kg canakinumab subcutaneous injection or placebo comparator in Part II and remained on the stable oral steroid dose for 24 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤ 0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤ 0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.
干预措施: canakinumab (Drug)
Placebo
Participants in Part II received placebo matching canakinumab subcutaneous injection every 4 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.
干预措施: placebo (Drug)
结局指标
主要结局
Part I: Percentage of Patients Who Were on Steroids at Entry Into Part I and Who Were Able to Taper Steroid as Per Protocol in at Least 25% of the Patients Who Entered the Study Taking a Steroid
时间窗: 32 Weeks
Ability to taper oral steroids: if dose reduced from start of Part I to end of Part Ic from \> 0.8 mg/kg/day to ≤ 0.5 mg/kg/day, or from ≥ 0.5 mg/kg/day and ≤ 0.8 mg/kg/day by at least 0.3 mg/kg, or from any initial dose to ≤ 0.2 mg/kg/day, while maintaining a minimum adapted ACR 30 pediatric criterion. Patients on oral steroids at study entry who did not enter Part 1c are considered steroid tapering failures.
Part II: Survival Estimate of Time to Flare
时间窗: Part II was event driven. The study was stopped when the required number of 37 flares had occurred (88 weeks)
Kaplan Meier estimate of the probability to experience a flare. Flare was defined as at least 1 of the following. * Reappearance of fever (\>38°C, lasting for at least 2 consecutive days) not due to infections * Flare according to the JIA pediatric criteria for flare (all criteria must have been met): * ≥ 30% worsening in at least 3 of the first 6 response variables * ≥ 30% improvement in not more than 1 of the first 6 response variables Patients who discontinued the study while in Part II were counted as flared unless they discontinued because of inactive disease for at least 24 weeks in Part II.
次要结局
- Part I: Percentage of Patients on Steroids at Study Start Who Reached a Steroid Dose ≤0.2 mg/kg at End of Part Ic(28 Weeks)
- Part I: Percentage of Participants on Steroids at the Start of 1c Who Were Able to Taper Steroids by the End of Part 1c(Start of Part Ic (After Week 8) to End of Part Ic (Week 28))
- Part I: Percentage of Participants With Minimum American College of Rheumatology (ACR) 30/50/70/90/100 at the End of Part I(Baseline, 32 Weeks)
- Part I: Time to First Minimum American College of Rheumatology (ACR50) and Normal C-Reactive Protein(Baseline, Week 32)
- Part I: Time to First Minimum American College of Rheumatology (ACR70) and Normal C-Reactive Protein(Baseline, Week 32)
- Part I: Percentage of Participants With Body Temperature ≤ 38 Degrees Celsius at Day 3 in Part 1a(Day 3)
- Part II: Survival Analysis of Time to a Worsening in American College of Rheumatology (ACR) Response(Part II was event driven. The study was stopped when the required number of 37 flares had occurred (88 weeks))
- Part I: Change in Disability Over Time in the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI) From Baseline to End of Part I(Baseline, End of Part I (Week 32))
- Part II: Change in Disability Over Time by the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI)(Start of Part II (Week 32), End of Part II ( total duration-88 weeks))
- Part I: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)(Baseline, End of Part I ( Week 32))
- Part II: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)(Start Part II (Week 32), End Part II (total duration - 88 Weeks))