β-SPECIFIC 4 Patients: Study of Pediatric EffiCacy and Safety wIth FIrst-line Use of Canakinumab An Open-label Canakinumab (ACZ885) Dose Reduction or Dose Interval Prolongation Efficacy and Safety Study in Patients With Systemic Juvenile Idiopathic Arthritis (SJIA)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 182
- 试验地点
- 1
- 主要终点
- Number of Participants in Clinical Remission on Canakinumab Who Are Able to Remain at an Initial Reduced Canakinumab Dose or Prolonged Canakinumab Dose Interval.
研究概览
简要总结
The purpose of this study was to evaluate the efficacy observed with canakinumab dose reduction in a subgroup of patients in the extension study CACZ885G2301E1.
详细描述
This two-part open-label study was to assess 2 different canakinumab taper regimens in patients with clinical remission (inactive disease for at least 24 continuous weeks) on canakinumab treatment without concomitant corticosteroids (CS) or methotrexate (MTX). The study was also to collect long term safety and tolerability data on SJIA patients treated with canakinumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
No blinding was required in this open-label study
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
- •Patients who are receiving canakinumab treatment (4 mg/kg every 4 weeks) for Systemic Juvenile Idiopathic Arthritis (SJIA) and have inactive disease at the last visit in Study CACZ885G2301E1
- •Confirmed diagnosis of SJIA as per International League Against Rheumatism (ILAR) definition that must have occurred at least 2 months prior to enrollment with an onset of disease < 16 years of age.
- •Active SJIA defined as having 2 or more of the following:
- •Documented spiking, intermittent fever (body temperature > 38°C) for at least 1 day within 1 week before first canakinumab dose;
- •At least 2 joints with active arthritis
- •C-reactive protein (CRP) > 30 mg/L (normal range < 10 mg/L)
- •Rash due to SJIA
- •Serositis
- •Lymphadenopathy
- •Hepatosplenomegaly
- •Negative TB screen (QuantiFERON or, if required by local guidelines, Purified Protein Derivative).
排除标准
- •With active or recurrent bacterial, fungal or viral infection at the time of enrollment, including patients with evidence of Human Immunodeficiency Virus (HIV) infection, Hepatitis B and Hepatitis C infection.
- •With underlying metabolic, renal, hepatic, infectious or gastrointestinal conditions which in the opinion of the investigator immunocompromises the patient and /or places the patient at unacceptable risk for participation.
- •With neutropenia (absolute neutrophil count < 1500/mm3) at screening.
研究组 & 干预措施
Canakinumab Dose Reduction
All patients received canakinumab 4mg/kg (300 mg max) every 4 weeks in Part I of the study. Patients eligible for Part II of the study were randomized to one of two treatment arms. This is Treatment Arm 1 in Part II of the study: Canakinumab was administered at a reduced dose (2 mg/kg every 4 weeks). If the patient continued to maintain inactive disease for 24 additional weeks, canakinumab was administered at 1mg/kg every 4 weeks. If the patient continued to maintain inactive disease for another 24 additional weeks, canakinumab treatment was discontinued.
干预措施: ACZ885 150 mg (Canakinumab) (Drug)
Canakinumab Dose Interval Prolongation
All participants received canakinumab 4mg/kg (300 mg max) every 4 weeks in Part I of the study. Patients eligible for Part II of the study were randomized to one of two treatment arms. This is Treatment Arm 2 in Part II of the study: Canakinumab dose interval was prolonged to a regimen of 4mg/kg every 8 weeks. If the patient continued to be stable with inactive disease for 24 additional weeks, canakinumab dose interval was prolonged to a regimen of 4mg/kg every 12 weeks. If the patient was clinically stable with inactive disease for another 24 additional weeks, canakinumab treatment was discontinued.
干预措施: ACZ885 150 mg (Canakinumab) (Drug)
结局指标
主要结局
Number of Participants in Clinical Remission on Canakinumab Who Are Able to Remain at an Initial Reduced Canakinumab Dose or Prolonged Canakinumab Dose Interval.
时间窗: baseline to 24 weeks
The primary efficacy variable for Part II was the proportion of patients in clinical remission on canakinumab 4 mg/kg (+/- concomitant NSAID only) who were able to remain on a reduced dose or on prolonged dose interval for at least 24 consecutive weeks. As the primary objective was to show statistically significance in at least one of canakinumab treatment arms (reduced dose and prolonged dose interval arms) in Part II then the Type I error rate 5% was controlled and split to 2.5%. Clinical remission per protocol is defined as the maintenance of inactive disease for at least 6 months (24consecutive weeks) while on therapy. The primary analysis considered both inactive disease status and the patient dose step duration. In the event the inactive disease status was missing, yet the patient remained at the same dose level through the next visit with the same disease status, it was concluded that inactive disease was maintained during this time period and was carried forward.
次要结局
- Number and Percentage of Patients With Adverse Events as a Measure of Long-term Safety and Tolerability of Canakinumab - PART 1(During study parts I and II. The estimated study duration is not more than 216 weeks (with an average expected duration of 108 weeks).)
- Number and Percentage of Patients With Adverse Events as a Measure of Long-term Safety and Tolerability of Canakinumab - PART 2(During study parts I and II, estimated study duration was not more than 216 weeks (with an average duration of 108 weeks).)