A Randomized, Double-blind, Placebo Controlled, Multicenter, Phase III Study of Subcutaneous Secukinumab to Compare Efficacy at 16 Weeks With Placebo and to Assess Safety and Tolerability up to 52 Weeks in Chinese Participants With Active Non-radiographic Axial Spondyloarthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 137
- 试验地点
- 29
- 主要终点
- Assessment of SpondyloArthritis International Society 40 (ASAS40) Response Rate in TNF-alpha-inhibitor-naive Participants at Week 16
研究概览
简要总结
The purpose of this study was to evaluate the efficacy, safety, and tolerability of secukinumab in Chinese patients with active non-radiographic axial spondyloarthritis (nr-axSpA).
详细描述
This was a randomized, double-blind, placebo-controlled study. Approximately 134 participants were planned to be randomized in a 1:1 ratio to receive secukinumab 150 mg subcutaneously (s.c.) or placebo.
The double-blind treatment period lasted for 16 weeks. At the end of this period, all participants, including those who initially received placebo, switched to open-label treatment with secukinumab 150 mg s.c.
The first dose of open-label treatment was administered at the Week 16 visit, after completing all necessary assessments for that visit. However, the participants and investigators remained blinded to the original treatment assignment. At Week 24, participants who did not respond to the treatment (defined as not achieving Ankylosing SpondyloArthritis International Society 20 [ASAS20] response) were given a higher dose of secukinumab (300 mg s.c.), while responders continued with the 150 mg s.c. dose. The study treatment continued until Week 48. Four weeks after the last study treatment administration, an end-of-treatment visit was conducted at Week 52.
Additionally, a post-treatment safety follow-up visit was performed 12 weeks after the last study treatment administration for all participants, whether they completed the entire study as planned or exited early.
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
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or non-pregnant, non-nursing female patients at least 18 years of age
- •Diagnosis of axial spondyloarthritis according to Ankylosing SpondyloArthritis International Society (ASAS) axial spondyloarthritis criteria
- •Objective signs of inflammation (magnetic resonance imaging (MRI) or abnormal C-reactive protein)
- •Active axial spondyloarthritis as assessed by total Bath Ankylosing Spondylitis Disease Activity Index >=4 cm
- •Spinal pain as measured by Bath Ankylosing Spondylitis Disease Activity Index question #2 ≥ 4 cm (0-10 cm) at baseline
- •Total back pain as measured by Visual Analogue scale ≥ 40 mm (0-100 mm) at baseline
- •Patients should have been on at least 2 different non-steroidal anti-inflammatory drugs with an inadequate response
- •Patients who have been on a TNFα inhibitor (not more than one) must have experienced an inadequate response
排除标准
- •Patients with radiographic evidence for sacroiliitis, grade ≥ 2 bilaterally or grade ≥ 3 unilaterally
- •Inability or unwillingness to undergo MRI
- •Chest X-ray or MRI with evidence of ongoing infectious or malignant process
- •Patients taking high potency opioid analgesics
- •Previous exposure to secukinumab or any other biologic drug directly targeting interleukin-17 (IL-17) or IL-17 receptor
- •Pregnant or nursing (lactating) women
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Placebo
Participants initially received a placebo in a pre-filled syringe (PFS) in a double-blinded manner until Week 12. At Week 16, they switched to an open-label treatment of secukinumab 150 mg. At Week 24, non-responders (not achieving ASAS20) were escalated to secukinumab 300 mg, while responders continued with secukinumab 150 mg.
干预措施: Placebo (Drug)
Secukinumab
Participants received secukinumab 150 mg in a pre-filled syringe (PFS). Treatment was double-blinded until Week 12. From Week 16, participants continued with an open-label treatment of secukinumab 150 mg. At Week 24, non-responders (not achieving ASAS20) were escalated to secukinumab 300 mg, while responders continued with secukinumab 150 mg.
干预措施: Secukinumab (Drug)
结局指标
主要结局
Assessment of SpondyloArthritis International Society 40 (ASAS40) Response Rate in TNF-alpha-inhibitor-naive Participants at Week 16
时间窗: Baseline, Week 16
ASAS40 response was defined as relative improvement of at least 40% and absolute improvement of at least 2 units on a 0 to 10 scale in at least 3 of the 4 main domains of the ASAS and no worsening at all in the remaining domain. The 4 main domains of the ASAS are: 1.Patient's Global Assessment of Disease Activity (score ranged from 0 \[not active\] to 10 \[very active\]); 2.Back Pain (score ranged from 0 \[no pain\] to 10 \[severe pain\]); 3.Function (Bath Ankylosing Spondylitis Functional Index \[BASFI\]) (score ranged from 0 \[easy\] to 10 \[impossible\]); 4.Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) (score ranged from 0 \[none\] to 10 \[very severe\]). The percentage of TNF-alpha-inhibitor-naïve participants who achieved ASAS40 response at Week 16 was assessed using a logistic regression model. Discontinued participants and those with missing responses were considered non-responders
次要结局
- ASAS40 Response Rate in All Participants at Week 16(Baseline, Week 16)
- ASAS 5/6 Response Rate at Week 16.(Baseline, Week 16)
- Change From Baseline in Total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score at Week 16(Baseline, Week 16)
- BASDAI 50 Rate at Week 16(Baseline, Week 16)
- Change From Baseline of High Sensitivity C-Reactive Protein (hsCRP) at Week 16(Baseline, Week 16)
- Change From Baseline in Total Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 16(Baseline, Week 16)
- Change From Baseline in Sacroiliac Joint (SIJ) Edema Score on Magentic Resonance Imaging (MRI) at Week 16(Baseline, Week 16)
- ASAS20 Response Rate at Week 16(Baseline, Week 16)
- Change From Baseline in Short Form-36 Physical Component Summary (SF-36 PCS) at Week 16(Baseline, Week 16)
- Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Scores at Week 16(Baseline, Week 16)
- ASAS Partial Remission Rate at Week 16(Baseline, Week 16)