A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Ustekinumab in the Treatment of Subjects With Active Nonradiographic Axial Spondyloarthritis
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 356
- 试验地点
- 93
- 主要终点
- Percentage of Participants Who Achieved Assessment of SpondyloArthritis International Society (ASAS) 20 Response at Week 24
研究概览
简要总结
The purpose of this study is to assess the efficacy and safety of ustekinumab in adult participants with active nonradiographic axial spondyloarthritis (nr-AxSpA) measured by the reduction in signs and symptoms of nonradiographic axial spondyloarthritis (nr-AxSpA).
详细描述
This is a phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of ustekinumab in the treatment of participants with active non-radiographic axial spondylo arthritis. Participants will receive either placebo or ustekinumab 45 or 90 milligram (mg). Participants will primarily be assessed for Assessment of Spondylo Arthritis (ASAS) International Society criteria 20 at Week 24. Safety will be monitored throughout the study.
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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must be classified as having nonradiographic axial spondyloarthritis (nr-AxSpA) based on 2009 Assessment of SpondyloArthritis International Society (ASAS) criteria
- •Must have an age at nr-AxSpA onset of <= 45 years
- •Must have at screening or active inflammation on magnetic resonance imaging (MRI) as evidenced by the central readers and no radiographic sacroiliitis that fulfills the 1984 modified New York Criteria
- •Must have symptoms of active disease at screening and at baseline, as evidenced by both a BASDAI score of >= 4 and a visual analogue scale (VAS) score for total back pain of more than or equal to (>=) 4, each on a scale of 0 to 10
排除标准
- •Have radiographic sacroiliitis fulfilling the 1984 modified New York Criteria
- •Have other inflammatory diseases that might confound the evaluations of benefit from the ustekinumab therapy
- •Have received any systemic immunosuppressives or disease-modifying anti-rheumatic drug (DMARDs) other than methotrexate (MTX), sulfasalazine (SSZ), or hydroxychloroquine (HCQ) within 4 weeks prior to first administration of study agent
- •Have received epidural, intra-articular, intramuscular (IM), or intravenous (IV) corticosteroids, including adrenocorticotropic hormone during the 4 weeks prior to first administration of study agent
- •Have received prior biologic therapy other than anti-TNFα
- •Have received more than 1 prior anti-TNFα agent
研究组 & 干预措施
Group 1: Placebo
Participants will receive placebo subcutaneously (SC) at Weeks 0, 4, 16, and 20. At Week 24, all participants (except those who early escaped) will crossover to receive ustekinumab 45 or 90 milligram (mg) SC at Weeks 24 and 28 followed by every 12 weeks up to Week 52. At Week 16, participants in placebo group with < 10% improvement from baseline in both total back pain and morning stiffness measures at Week 12 and 16 will enter early escape to receive ustekinumab 45 mg or 90 mg at Weeks 16, 20, and 28 followed by every 12 weeks up to Week 52. At Week 52, participants who achieved inactive disease by ASDAS (ESR) <1.3 at both Week 40 and 52 will be re-randomized to receive placebo or ustekinumab every 12 weeks up to Week 88. At Week 52, participants who did not achieve inactive disease by ASDAS (ESR) <1.3 at Week 40 or 52 will continue with ustekinumab every 12 weeks up to Week 88. NOTE: Intervention Description should have no more than 800 characters.
干预措施: Group 1: Placebo (Drug)
Group 2: Ustekinumab 45 milligram (mg)
Participants will receive ustekinumab 45 mg subcutaneously at Weeks 0 and 4, followed by every 12 weeks through Week 52. At Weeks 20 and 24, participants will receive placebo subcutaneously to maintain the blind. At Week 52, participants who achieved inactive disease by ASDAS (ESR) <1.3 at both Week 40 and Week 52 will be re-randomized to receive either placebo or ustekinumab 45 mg every 12 weeks in a blinded fashion. At Week 52, participants who did not achieve inactive disease by ASDAS (ESR) <1.3 at Week 40 or Week 52 will continue receiving ustekinumab 45 mg every 12 weeks through Week 88.
干预措施: Group 2: Ustekinumab 45 mg (Drug)
Group 3: Ustekinumab 90 mg
Participants will receive ustekinumab 90 mg subcutaneously at Weeks 0 and 4, followed by every four weeks through Week 52. At Weeks 20 and 24, participants will receive placebo subcutaneously to maintain the blind. At Week 52, participants who achieved inactive disease by ASDAS (ESR) <1.3 at both Week 40 and Week 52 will receive either placebo or ustekinumab 90 mg every 12 weeks in a blinded fashion. At Week 52, participants who did not achieve inactive disease by ASDAS (ESR) <1.3 at Week 40 or Week 52 will continue receiving ustekinumab 90 mg every 12 weeks through Week 88.
干预措施: Group 3: Ustekinumab 90 mg (Drug)
结局指标
主要结局
Percentage of Participants Who Achieved Assessment of SpondyloArthritis International Society (ASAS) 20 Response at Week 24
时间窗: Week 24
ASAS 20 defined as improvement of greater than or equal to (\>=) 20 % from baseline and absolute improvement from baseline of 1 on a 0 to 10 centimeter(cm) scale in at least 3 of following 4 domains: Patient's global assessment of disease activity (0 to 10 cm; 0=very well,10=very poor), total back pain (0 to 10 cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 to participant's ability to cope with everyday life), Inflammation (0 to 10 cm;0=none,10=very severe); absence of deterioration (\>= 20% and worsening of at least 1 on a 0 to 10 cm scale) from baseline in remaining domain. ASAS20 response based on imputed data using treatment failure (consider non-responders at and after treatment failure),early escape rules (consider non-responder at Week 20 and 24),non-responder\[NRI\] (missing responses at post baseline visit imputed as non-responder).
次要结局
- Percentage of Participants Who Achieved an ASAS 40 Response at Week 24(Week 24)
- Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24(Week 24)
- Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24(Baseline, Week 24)
- Percentage of Participants Who Achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) C-reactive Protein (CRP) Inactive Disease (<1.3) at Week 24(Week 24)
- Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24(Baseline, Week 4, 8, 12, 16, 20 and 24)
- Percentage of Participants With ASAS 20 Components at Week 24(Week 24)
- Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20(Week 4, 8, 12, 16 and 20)
- Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20(Week 4, 8, 12, 16 and 20)
- Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20(Week 4, 8, 12, 16, and 20)
- Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 4, 8, 12, 16 and 20(Baseline, Week 4, 8, 12, 16 and 20)
- Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16, and 20(Week 4, 8, 12, 16, and 20)