An Open-label, Single-arm, Active-treatment Study to Evaluate Efficacy and Safety of Canakinumab (ACZ885) Administered for at Least 48 Weeks in Japanese Patients With Adult Onset Still's Disease (AOSD)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 9
- 主要终点
- Percentage of Participants Who Achieved Adapted American College of Rheumatology (ACR) 30 Response at Week 8
研究概览
简要总结
This study was designed to evaluate the efficacy and safety of canakinumab administered subcutaneously every 4 weeks for at least 48 weeks in Japanese patients with Adult-Onset Still's Disease (AOSD).
Interim analysis data collected at Weeks 28 and 48 supported the registration submission of canakinumab for the indication of Adult Still's Disease (ASD) in Japan.
详细描述
This was a Phase III, open-label, single-arm active treatment study designed to evaluate the efficacy, safety, tolerability, and pharmacokinetics/pharmacodynamics (PK/PD) of canakinumab at a dose of 4 mg/kg (up to a maximum of 300 mg) administered subcutaneously every 4 weeks for at least 48 weeks in Japanese participants with ASD.
The study consisted of two epochs:
- Screening epoch: Day -28 to Day -1
- Open-label treatment epoch: Day 1 until either regulatory approval and commercial availability of canakinumab for adult Still's disease (ASD) in Japan, or study termination (whichever occurred first).
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
- 16 Years 至 100 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent had to be obtained prior to participation in the study. Parent's or legal guardian's written informed consent and child's assent, if appropriate, were required before any assessment was performed for participants < 20 years of age.
- •Japanese male and female participants aged ≥ 16 years were eligible.
- •Diagnosis of AOSD had to be confirmed as per Yamaguchi criteria, with disease onset at ≥ 16 years of age. The Yamaguchi criteria required at least five criteria, including two major criteria and no
排除标准
- •Participants had to have active disease at baseline, defined as follows:
- •Fever (body temperature > 38°C) due to AOSD for at least 1 day within 1 week before baseline
- •At least 2 active joints (tender or swollen)
- •CRP ≥ 10 mg/L
- •Exclusion Criteria:
- •Pregnant or nursing (lactating) female participants were excluded. Pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL) at the screening visit.
- •Participants with a history of significant hypersensitivity to the study drug or to biologics were excluded.
- •Participants with a history or evidence of active macrophage activation syndrome or disseminated intravascular coagulation within 6 months prior to enrollment were excluded.
- •Participants with underlying metabolic, renal, hepatic, infectious, or gastrointestinal conditions that, in the opinion of the investigator, compromised the participant and/or placed the participant at unacceptable risk for participation in immunomodulatory therapy were excluded.
- •Participants with active or recurrent bacterial, fungal, or viral infections at the time of enrollment, including evidence of HIV infection, Hepatitis B, or Hepatitis C, were excluded.
- •Participants with an absolute neutrophil count < 1500/mm³ at screening were excluded.
研究组 & 干预措施
Canakinumab
All participants received canakinumab as open-label study medication. Canakinumab was administered subcutaneously at a dose of 4 mg/kg every four weeks, with a maximum allowable single dose of 300 mg.
干预措施: Canakinumab (Biological)
结局指标
主要结局
Percentage of Participants Who Achieved Adapted American College of Rheumatology (ACR) 30 Response at Week 8
时间窗: Baseline, Week 8
Adapted ACR30 response was defined as a ≥30% improvement from baseline in at least 3 of the following 5 core response variables, with no more than one of these variables worsening by \>30%: 1. Physicians global assessment of disease activity (PhGA) on a 0-100 mm visual analogue scale (VAS) (0=very good and 100=very poor). 2. Participant's assessment of disease activity (PtGA) on a 0-100 mm VAS (0=very good and 100=very poor). 3. Health Assessment Questionnaire- disability index (HAQ-DI): 20 questions across 8 domains assessing the functional abilities. The total score was calculated as the average of the scores for each domain, ranging from 0 (no disability) to 3 (very severe disability). 4. Number of active joints (68 joints evaluated for pain/tenderness and 66 for swelling) 5. Index of inflammation: C-reactive Protein (CRP) levels Additionally, participants were required to have no intermittent fever during the preceding week.
次要结局
- Canakinumab Concentrations Over Time(Baseline (pre-dose), Day 3, Day 15, and pre-dose at Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192.)
- Number of Participants Who Were Able to Taper Corticosteroids Based on Success Criteria at Week 28.(Baseline, Week 28)
- Number of Participants Who Achieved Adapted ACR 30 Response Criteria(Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks))
- Number of Participants Who Achieved Adapted ACR 50 Response Criteria(Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks))
- Number of Participants Who Achieved Adapted ACR 70 Response Criteria(Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks))
- Number of Participants Who Achieved Adapted ACR 90 Response Criteria(Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks))
- Number of Participants Who Achieved Adapted ACR 100 Response Criteria(Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks))
- Change From Baseline in Systemic Feature Score (SFS)(Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks))
- Change From Baseline in the Component of Adapted ACR: Physician's Global Assessment of Disease Activity(aseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks))
- Change From Baseline in the Component of Adapted ACR: Patient's Global Assessment of Disease Activity(Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks))
- Change From Baseline in the Component of Adapted ACR: Health Assessment Questionnaire- Disability Index (HAQ-DI)(Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks))
- Change From Baseline in the Component of Adapted ACR: Number of Active Joints(Baseline, Day 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, End of Study (up to approx. 208 weeks))
- Change From Baseline in the Component of Adapted ACR: C-Reactive Protein (CRP) Levels(Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks))
- Total IL-1β Levels(Baseline (pre-dose), Day 3, Day 15, and pre-dose at Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192.)
- Number of Participants With Absence of Intermittent Fever in the Preceding Week (Component of the Adapted ACR)(Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks))
- Change From Baseline in Oral Corticosteroid Dose(Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, End of Study visit (assessed up to approx. 208 weeks))
- Number of Participants With or Without Rash (Typical vs. Atypical)(Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks))
- Change From Baseline in Disease Activity Score (DAS)28 - CRP(Baseline, Day 15, Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and End of Study visit (assesed up to approx. 208 weeks))
- Number of Participants With Canakinumab Anti-drug Antibodies (ADA)(Pre-dose at baseline, Weeks 24, 48, 72, 96, 120, 144)