A 52-Week Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ixekizumab (LY2439821) in bDMARD Naive Patients With Nonradiographic Axial Spondyloarthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 303
- 试验地点
- 38
- 主要终点
- Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) Response
研究概览
简要总结
The main purpose of this study is to evaluate the safety and efficacy of the study drug known as ixekizumab in biologic disease modifying antirheumatic drug (bDMARD) naïve participants with nonradiographic axial spondyloarthritis (nonrad-axSpA).
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
- Double (Participant, Investigator)
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
- •Are ambulatory.
- •Diagnosis of nonradiographic axial spondyloarthritis (nr-axSpA) and fulfilling the 2009 Assessment of Spondyloarthritis International Society (ASAS) classification criteria.
- •Have a history of back pain ≥3 months with age at onset <45 years.
- •Have active nr-axSpA defined as BASDAI ≥4 and total back pain ≥4 on a numeric rating scale (NRS) at screening and baseline.
- •Have objective signs of inflammation by presence of sacroiliitis on MRI and/or presence of elevated C-reactive protein (CRP).
- •In the past had an inadequate response to at least 2 non-steroidal anti-inflammatory drugs (NSAIDS) for duration of 4 weeks or cannot tolerate NSAIDS.
- •If taking NSAIDS be on stable dose for at least 2 weeks prior to randomization.
- •Have a history of prior therapy for axSpA for at least 12 weeks prior to screening.
排除标准
- •Have radiographic sacroiliitis fulfilling the 1984 modified New York criteria.
- •Have received any prior, or are currently receiving treatment with biologics, tumor necrosis factor inhibitors or other immunomodulatory agents.
- •Have received a live vaccine within 12 weeks or have had a vaccination with Bacillus Calmette-Guerin (BCG) within the past year.
- •Have an ongoing or serious infection within the last 12 weeks or evidence of active tuberculosis.
- •Have a compromised immune system.
- •Have any other serious and/or uncontrolled diseases.
- •Have either a current diagnosis or a recent history of malignant disease.
- •Have had major surgery within 8 weeks of baseline, or will require surgery during the study.
- •Are pregnant or breastfeeding.
- •Have evidence of active anterior uveitis (an acute episode) within the last 42 days prior to baseline randomization.
研究组 & 干预措施
Q2W Ixekizumab
Participants received a starting dose of 80 or 160 milligram (mg) of ixekizumab given subcutaneously (SC) at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52 during the double-blind period.
Inadequate responders (IR) as determined by investigators could switch to ixekizumab 80 mg Q2W open label between week 16 and 44.
干预措施: Ixekizumab (Drug)
Q4W Ixekizumab
Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52 during the double-blind period.
Inadequate responders as determined by investigators could switch to ixekizumab 80 mg Q2W open label week 16 and 44.
干预措施: Ixekizumab (Drug)
Placebo
Participants received placebo as 2 SC injections Q2W to week 52 during double-blind period.
Inadequate responders as determined by investigators could switch to ixekizumab 80 mg Q2W open label between week 16 and 44.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) Response
时间窗: Week 16
ASAS40 is defined as a greater than or equal to (≥)40% improvement and an absolute improvement from baseline of ≥2 units (ranges 0 to 10) in at least 3 of the 4 domains (Patient Global, Spinal Pain, Function, and Inflammation), without any worsening in the remaining domain. 1) Patient Global: How active was your spondylitis during the last week? score ranges 0 (not active) to 10 (very active). 2) Spinal Pain: How much spinal pain due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). 3) Bath Ankylosing Spondylitis Functional Index: Participant is asked to rate the difficulty associated with 10 individual basic functional activities. Responses were captured using numeric rating scale (NRS) (ranges 0 to 10) with a higher score of worse function. 4) Inflammation based on mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) question 5 and 6 (mean of intensity, duration of stiffness). Score ranges (0 (non) to 10 (very severe).
Percentage of Participants Achieving an ASAS40 Response
时间窗: Week 52
ASAS40 is defined as a greater than or equal to (≥)40% improvement and an absolute improvement from baseline of ≥2 units (ranges 0 to 10) in at least 3 of the 4 domains (Patient Global, Spinal Pain, Function, and Inflammation), without any worsening in the remaining domain. 1) Patient Global: How active was your spondylitis during the last week? score ranges 0 (not active) to 10 (very active). 2) Spinal Pain: How much spinal pain due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). 3) Bath Ankylosing Spondylitis Functional Index: Participant is asked to rate the difficulty associated with 10 individual basic functional activities. Responses were captured using numeric rating scale (NRS) (ranges 0 to 10) with a higher score of worse function. 4) Inflammation based on mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) question 5 and 6 (mean of intensity, duration of stiffness). Score ranges (0 (non) to 10 (very severe).
次要结局
- Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS)(Baseline, Week 52)
- Number of Participants Without Clinically Meaningful Changes in Background Therapy(Baseline through Week 52)
- Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score(Baseline, Week 52)
- Percentage of Participants Achieving ASDAS Low Disease Activity(Week 52)
- Change From Baseline in Magnetic Resonance Imaging (MRI) of the Sacroiliac Joint (SIJ) Spondyloarthritis Research Consortium of Canada (SPARCC) Score(Baseline, Week 16)
- Change From Baseline in SPARCC Enthesitis Score(Baseline, Week 52)
- Change From Baseline in the Measure of High Sensitivity C-Reactive Protein (CRP)(Baseline, Week 52)
- Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)(Baseline, Week 52)
- Change From Baseline in Chest Expansion(Baseline, Week 52)
- Change From Baseline in Occiput to Wall Distance(Baseline, Week 52)
- Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)(Baseline, Week 52)
- Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)(Baseline, Week 52)
- Percentage of Participants Achieving ASDAS Inactive Disease(Week 52)
- Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)(Baseline, Week 52)
- Change From Baseline in Severity of Peripheral Arthritis by Tender (TJC) and Swollen Joint Count (SJC) Scores of 44 Joints(Baseline, Week 52)
- Number of Participants With Anterior Uveitis(Baseline through Week 52)
- Change From Baseline in the Fatigue Numeric Rating Scale (NRS) Score(Baseline, Week 52)
- Change From Baseline in ASAS Health Index (ASAS HI)(Baseline, Week 52)
- Change From Baseline in the Jenkins Sleep Evaluation Questionnaire (JSEQ)(Baseline, Week 52)
- Change From Baseline in the Work Productivity Activity Impairment Spondyloarthritis (WPAI-SpA) Scores(Baseline, Week 52)
- Change From Baseline in ASAS-Nonsteroidal Anti-Inflammatory Drug (NSAID) Score(Baseline, Week 52)
- Number of Participants With Treatment Emergent (TE) Anti-Ixekizumab Antibodies(Week 52)
- Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough ss)(Week 52)