A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Filgotinib in Subjects With Active Ankylosing Spondylitis Who Have an Inadequate Response to Biologic Disease-Modifying Antirheumatic Drug Therapy
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 主要终点
- Proportion of Participants Who Achieve an Assessment of SpondyloArthritis international Society 40% Improvement (ASAS40) Response at Week 16
研究概览
简要总结
The primary objective of this study is to evaluate the effect of filgotinib versus placebo on signs and symptoms of active ankylosing spondylitis (AS), evaluated by Assessment of SpondyloArthritis international Society 40% improvement (ASAS40) response at Week 16 in participants with active AS who have an inadequate response to biologic disease-modifying antirheumatic drug therapy.
详细描述
The study consists of 2 parts: Main Study (screening through Week 16) and Long-Term Extension (LTE) (up to 1.5 years after Week 16). Participants who permanently discontinue treatment in the Main Study will not be eligible for the Long-Term extension.
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
- •Ambulatory male or female individuals who are ≥ 18 years of age (≥ 20 years of age in Japan) on the day of signing informed consent
- •Have had inadequate response or intolerance to at least 1 and not more than 3 biologic disease-modifying antirheumatic drugs (bioDMARDs) administered for the treatment of ankylosing spondylitis (AS) or inflammatory arthritis
- •Have an established diagnosis of radiographic axial spondyloarthritis (SpA)/ AS by a rheumatologist (or other specialist with expertise in diagnosing AS)
- •Meet Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA with radiographic sacroiliitis on imaging at screening as follows:
- •History of back pain ≥ 3 months and age at onset of back pain < 45 years, AND
- •Radiographic sacroiliitis Grade ≥ 2 bilaterally or Grade 3-4 unilaterally, AND
- •≥ 1 SpA feature (refer to protocol; inflammatory back pain, arthritis, heel enthesitis, uveitis anterior, dactylitis, psoriasis, inflammatory bowel disease (IBD), good response to nonsteroidal anti-inflammatory drugs (NSAIDs), family history of SpA, historically positive human leukocyte antigen B27 (HLA-B27), elevated C-reactive protein (CRP))
- •Have active AS at screening and Day 1 as defined by:
- •Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4, AND
- •Spinal pain ≥ 4 (based on BASDAI question 2)
- •Have a history of inadequate response or intolerance to NSAIDs for the treatment of AS
- •If using allowed conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), NSAID, or corticosteroid therapy, must have been on stable doses (as outlined in protocol) prior to Day 1
排除标准
- •Prior exposure to a Janus kinase (JAK) inhibitor > 2 doses
- •Total ankylosis of the spine
- •Any active/recent infection, as specified in the protocol
- •Diagnosis of fibromyalgia
- •Any musculoskeletal disorder other than AS that would interfere with assessment of study parameters, as per judgement of investigator
- •Note: Prior history of reactive or other types of inflammatory arthritis is permitted if there is documentation of change in diagnosis to AS or additional diagnosis of AS
- •Any history of an inflammatory arthritis with onset age before 16 years old
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Filgotinib 200 mg (Main Study - Blinded)
Participants will receive filgotinib 200 mg + placebo to match (PTM) filgotinib 100 mg for up to 16 weeks.
干预措施: Filgotinib (Drug)
Filgotinib 200 mg (Main Study - Blinded)
Participants will receive filgotinib 200 mg + placebo to match (PTM) filgotinib 100 mg for up to 16 weeks.
干预措施: Placebo to Match Filgotinib (Drug)
Filgotinib 100 mg (Main Study - Blinded)
Participants will receive filgotinib 100 mg + PTM filgotinib 200 mg for up to 16 weeks.
干预措施: Filgotinib (Drug)
Filgotinib 100 mg (Main Study - Blinded)
Participants will receive filgotinib 100 mg + PTM filgotinib 200 mg for up to 16 weeks.
干预措施: Placebo to Match Filgotinib (Drug)
Placebo (Main Study - Blinded)
Participants will receive PTM filgotinib 200 mg + PTM filgotinib 100 mg for up to 16 weeks.
干预措施: Placebo to Match Filgotinib (Drug)
Filgotinib 200 mg (LTE)
Before study-wide unblinding, participants will receive filgotinib 200 mg + PTM filgotinib 100 mg.
After study-wide unblinding, participants will receive filgotinib 200 mg.
干预措施: Filgotinib (Drug)
Filgotinib 200 mg (LTE)
Before study-wide unblinding, participants will receive filgotinib 200 mg + PTM filgotinib 100 mg.
After study-wide unblinding, participants will receive filgotinib 200 mg.
干预措施: Placebo to Match Filgotinib (Drug)
Filgotinib 100 mg (LTE)
Before study-wide unblinding, participants will receive filgotinib 100 mg + PTM filgotinib 200 mg.
After study-wide unblinding, participants will receive filgotinib 100 mg.
干预措施: Filgotinib (Drug)
Filgotinib 100 mg (LTE)
Before study-wide unblinding, participants will receive filgotinib 100 mg + PTM filgotinib 200 mg.
After study-wide unblinding, participants will receive filgotinib 100 mg.
干预措施: Placebo to Match Filgotinib (Drug)
结局指标
主要结局
Proportion of Participants Who Achieve an Assessment of SpondyloArthritis international Society 40% Improvement (ASAS40) Response at Week 16
时间窗: Week 16
The ASAS40 calculation involves the analysis of 4 domains: participant's global assessment of disease activity, spinal pain (derived from the spinal pain questionnaire), function (derived from Bath Ankylosing Spondylitis Functional Index (BASFI) score), and inflammation (derived from morning stiffness questions from Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)). The ASAS40 is achieved if there is an improvement of ≥ 40% and ≥ 2 units in at least 3 domains on a scale of 10 with no worsening in the remaining domain.
次要结局
- Change From Baseline in Assessment of SpondyloArthritis international Society Health Index (ASAS HI)(Baseline and up to Week 16)
- Change From Baseline in Physical Component Summary (PCS) Score of the 36-Item Short-Form Survey (SF-36) Version 2(Baseline and up to Week 16)
- Change From Baseline in Mental Component Summary (MCS) Score of the SF-36 Version 2(Baseline and up to Week 16)
- Change from Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue)(Baseline and up to Week 16)
- Change From Baseline in Work Productivity and Activity Impairment for Ankylosing Spondylitis (WPAI-AS)(Baseline and up to Week 16)
- Change From Baseline in ASDAS(Baseline and up to Week 16)
- Proportion of Participants who achieve Ankylosing Spondylitis Disease Activity Score (ASDAS) Low Disease Activity (LDA) (ie, ASDAS < 2.1) at Week 16(Week 16)
- Proportion of Participants Who Achieve an ASAS40 Response(Up to Week 12)
- Proportion of Participants Who Achieve an Assessment of SpondyloArthritis international Society 20% Improvement (ASAS20) Response(Up to Week 16)
- Proportion of Participants Who Achieve an ASAS 5/6 Response(Up to Week 16)
- Change from Baseline in the Individual Components of the ASAS Core Set(Baseline and up to Week 16)
- Proportion of Participants Who Achieve a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50% Improvement Response(Up to Week 16)
- Change From Baseline in Chest Expansion(Baseline and up to Week 16)
- Change From Baseline in Occiput-to-wall Distance(Baseline and up to Week 16)
- Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL)(Baseline and up to Week 16)
- Change From Baseline in BASDAI(Baseline and up to Week 16)
- Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)(Baseline and up to Week 16)
- Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) (Linear Score)(Baseline and up to Week 16)
- Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), in Participants With Enthesitis at Baseline(Baseline and up to Week 16)
- Change From Baseline in EuroQol 5 Dimensions 5 Levels (EQ-5D-5L)(Baseline and up to Week 16)