A Randomized, Double-blind, Placebo-controlled Multicenter Study of Secukinumab 150 mg in Patients With Active nr- axSpA to Evaluate the Safety,Tolerability and Efficacy up to 2 Yrs, Followed by an Opt Phase of Either 150 mg or 300 mg Randomized Dose Escalation for up to Another 2 Yrs
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 555
- 试验地点
- 1
- 主要终点
- The Number and Percentage of TNF Naive Participants Who Achieved an Assessment of Spondylo Arthritis International Society (ASAS) 40 Response at Week 16
研究概览
简要总结
The purpose of this study was to demonstrate the clinical efficacy, safety and tolerability of secukinumab compared to placebo in patients with nr-axSpA at Week 16 as well as Week 52 and long term efficacy and safety up to Week 104 (core phase) followed by an optional extension phase consisting of a 16-week randomized dose escalation treatment period and a continuous treatment period for up to Week 208
详细描述
Patients were randomized to one of three treatment groups (1:1:1) in the core phase:
- Secukinumab 150 mg Load: secukinumab 150 mg (1 mL, 150 mg/mL) s.c. pre-filled syringe (PFS) at baseline, Weeks 1, 2, and 3, followed by administration every four weeks starting at Week 4
- Secukinumab 150 mg No Load: secukinumab 150 mg (1 mL, 150 mg/mL) s.c. PFS at baseline, placebo at Weeks 1, 2, and 3, followed by secukinumab 150 mg PFS administration every four weeks starting at Week 4
- Placebo: placebo (1 mL) s.c. PFS at baseline, Weeks 1, 2, 3, followed by administration every four weeks starting at Week 4.
All patients received secukinumab 150 mg as open-label treatment from Week 52 up to Week 100, unless they had discontinued study treatment.
At Week 104, all patients who finished the core phase according to the protocol were asked to continue in an optional, exploratory extension phase. Patients who achieved ASAS20 response at Week 104 (Core Phase Responders) were randomized to the following treatment groups (blinded) in the extension phase:
- Core Phase Responder 150 mg: secukinumab 150 mg (1 mL, 150 mg/mL) s.c. PFS and placebo (1 mL) s.c. PFS every four weeks;
- Core Phase Responder 300 mg: 2 injections with secukinumab 150 mg (1 mL, 150 mg/mL) s.c. PFS every four weeks.
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 —（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 Tumor Necrosis Factor (TNF) α 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
研究组 & 干预措施
Secukinumab, 150 mg Load (Core phase)
Secukinumab 150 mg s.c., pre-filled syringe (PFS) at baseline, Weeks 1, 2, and 3, followed by administration every four weeks starting at Week 4, Load, Core phase
干预措施: Secukinumab (Drug)
Secukinumab, 150 mg No Load (Core phase)
Secukinumab 150 mg s.c. PFS at baseline, placebo at Weeks 1, 2, and 3, followed by secukinumab 150 mg PFS administration every four weeks starting at Week 4, No Load, Core phase
干预措施: Secukinumab (Drug)
Placebo (Core phase)
Placebo s.c., PFS at baseline, Weeks 1, 2, 3, followed by administration every four weeks starting at Week 4, Core phase
干预措施: Placebo (Drug)
Core Phase Responder 150 mg (Extension phase)
Core Phase Responder 150 mg blinded: secukinumab 150 mg s.c. PFS and placebo (1 mL) s.c. PFS every four weeks, in the Extension phase
干预措施: Secukinumab (Drug)
Core Phase Responder 150 mg (Extension phase)
Core Phase Responder 150 mg blinded: secukinumab 150 mg s.c. PFS and placebo (1 mL) s.c. PFS every four weeks, in the Extension phase
干预措施: Placebo (Drug)
Core Phase Responder 300 mg (Extension phase)
Core Phase Responder 300 mg blinded: 2 injections with secukinumab 150 mg s.c. PFS every four weeks, in the Extension phase
干预措施: Secukinumab (Drug)
Core Phase Non-Responder 300 mg (Extension phase)
Core Phase Non-Responder 300 mg: 2 injections with secukinumab 150 mg s.c. PFS every four weeks open-label, in the Extension phase
干预措施: Secukinumab (Drug)
结局指标
主要结局
The Number and Percentage of TNF Naive Participants Who Achieved an Assessment of Spondylo Arthritis International Society (ASAS) 40 Response at Week 16
时间窗: Week 16
Assessment of SpondyloArthritis International Society criteria (ASAS) consist of 6 domains (4 main and 2 additional assessment domains): 1. Patient's global assessment measured on a visual analog scale (VAS); 2. Patient's assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions as measured by VAS; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) as measured by VAS; 5. Spinal mobility represented by the Bath Ankylosing Spondylitis Metrology Index (BASMI) lateral spinal flexion assessment; 6. C-reactive protein (acute phase reactant). ASAS40 response is defined as an improvement of ≥40% and ≥2 units on a scale of 10 in at least three of the four ASAS main domains and no worsening at all in the remaining domain. A higher score on the VAS signifies higher severity.
The Number and Percentage of TNF Naive Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 40 Response at Week 52
时间窗: Week 52
Assessment of SpondyloArthritis International Society criteria (ASAS) consist of 6 domains (4 main and 2 additional assessment domains): 1. Patient's global assessment measured on a visual analog scale (VAS); 2. Patient's assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions as measured by VAS; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) as measured by VAS; 5. Spinal mobility represented by the Bath Ankylosing Spondylitis Metrology Index (BASMI) lateral spinal flexion assessment; 6. C-reactive protein (acute phase reactant). ASAS40 response is defined as an improvement of ≥40% and ≥2 units on a scale of 10 in at least three of the four ASAS main domains and no worsening at all in the remaining domain. A higher score on the VAS signifies higher severity.
次要结局
- The Number and Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 40 Response(Week 16 and week 52)
- The Number and Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 20 Response(Week 16)
- The Number and Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 5/6 Response(Week 16)
- The Number and Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society Partial Remission (ASAS PR)(Week 16)
- Change in Bath Ankylosing Spondylitis Functional Index (BASFI)(Baseline and Week 16)
- The Number and Percentage of Patients to Achieve a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response(Week 16 and 52)
- Change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)(Baseline and Week 16)
- Change in Ankylosing Spondylitis Quality of Life (ASQoL) Scores at Week 16(Baseline and Week 16)
- Change in Ankylosing Spondylitis Quality of Life (ASQoL) Scores at Week 52(Baseline and Week 52)
- The Number and Percentage of Patients Who Achieved an Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-Reactive Protein (CRP) Inactive Disease(Week 52)
- Change in High Sensitivity C-reactive Protein(Baseline and Week 16)
- Change in Short Form-36 Physical Component Summary (SF-36 PCS)(Baseline and Week 16)
- Change in Sacroiliac Joint Edema - Week 16(Baseline and Week 16)
- Change in Sacroiliac Joint Edema - Week 52(Baseline and Week 52)