A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Bimekizumab in Subjects With Active Nonradiographic Axial Spondyloarthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 274
- 试验地点
- 83
- 主要终点
- Percentage of Participants With Assessment of SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 16
研究概览
简要总结
The purpose of the study is to demonstrate the efficacy, safety and tolerability of bimekizumab administered subcutaneously (sc) compared to placebo in the treatment of subjects with active nonradiographic axial spondyloarthritis (nr-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
- 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 female patients at least 18 years of age
- •Patient has nonradiographic axial spondyloarthritis (nr-axSpA) with all of the following criteria:
- •Adult-onset axial spondyloarthritis meeting Assessment of SpondyloArthritis International Society (ASAS) classification criteria
- •Inflammatory back pain for at least 3 months
- •Age at symptom onset of less than 45 years
- •NO sacroiliitis (in Anterior-Posterior pelvis or sacroiliac x-ray)
- •Active disease defined by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >=4 AND spinal pain >=4 on a 0 to 10 Numeric Rating Scale
- •Objective inflammation defined by sacroiliitis on magnetic resonance imaging and/or elevated C-reactive protein
- •Subjects had to have either failed to respond to 2 different nonsteroidal anti-inflammatory drugs (NSAIDs) given at the maximum tolerated dose for a total of 4 weeks or have a history of intolerance to or a contraindication to NSAID therapy
- •Patients who have taken a tumor necrosis factor alpha (TNFα) inhibitor must have experienced an inadequate response or intolerance to treatment given at an approved dose for at least 12 weeks
- •Patients currently taking NSAIDs, cyclooxygenase 2 (COX-2) inhibitors, analgesics, corticosteroids, methotrexate (MTX), leflunomide (LEF), sulfasalazine (SSZ), hydroxychloroquine (HCQ) AND/OR apremilast can be allowed if they fulfill specific requirements prior to study entry
排除标准
- •Treatment with more than 1 TNFα inhibitor and/or more than 2 additional non-TNFα biological response modifiers, or any interleukin (IL)-17 biological response modifier
- •Active infection or history of recent serious infections
- •Viral hepatitis B or C or human immunodeficiency virus (HIV) infection
- •Any live (includes attenuated) vaccination within the 8 weeks prior to entering the study or TB (Bacillus Calmette-Guerin) vaccination within 1 year prior entering the study
- •Known tuberculosis (TB) infection, at high risk of acquiring TB infection, or current or history of nontuberculous mycobacterium (NTMB) infection
- •Subject has any active malignancy or history of malignancy within 5 years prior to the Screening Visit EXCEPT treated and considered cured cutaneous squamous or basal cell carcinoma or in situ cervical cancer
- •Diagnosis of inflammatory conditions other than axial spondyloarthritis (axSpA), including but not limited to psoriatic arthritis, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, and reactive arthritis. Patients with a diagnosis of Crohn's disease, ulcerative colitis, or other inflammatory bowel disease (IBD) are allowed as long as they have no active symptomatic disease when entering the study
- •Presence of active suicidal ideation, or moderately severe major depression or severe major depression
- •Female patients who are breastfeeding, pregnant, or planning to become pregnant during the study
- •Subject has a history of chronic alcohol or drug abuse within 6 months prior to Screening
研究组 & 干预措施
Bimekizumab
Subjects randomized to this arm will receive bimekizumab during the Double-Blind Treatment Period and the Maintenance Period.
干预措施: Bimekizumab (Drug)
Placebo
Subjects randomized to this arm will receive placebo during the Double-Blind Treatment Period and receive bimekizumab during the Maintenance Period.
干预措施: Bimekizumab (Drug)
Placebo
Subjects randomized to this arm will receive placebo during the Double-Blind Treatment Period and receive bimekizumab during the Maintenance Period.
干预措施: Placebo (Other)
结局指标
主要结局
Percentage of Participants With Assessment of SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 16
时间窗: Week 16
ASAS40 response is defined as relative improvements of at least 40% and absolute improvement of at least 2 units in at least 3 of the 4 following components:1) Patient's Global Assessment of Disease Activity (PGADA) assessed on a scale ranging from 0 \[not active\] to 10 \[very active\], higher score=higher disease activity, 2) Spinal Pain assessed on a scale ranging from 0 \[no pain\] to 10 \[most severe pain\], higher score= higher pain intensity, 3) Bath Ankylosing Spondylitis Functional Index (BASFI) assessing participant's level of ability on a scale ranging from 0 \[easy\] to 10 \[impossible\] on 10 physical activities,4) morning stiffness, assessed as the mean of Q5 (intensity) and Q6 (duration) from the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), each assessed on a scale ranging from 0 \[none / 0 hour\] to 10 \[very severe / 2 or more hours\], higher score=higher severity; and no worsening at all in the remaining component.
次要结局
- Percentage of Participants With Assessment of SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response in TNFα Inhibitor-naïve Subjects at Week 16(Week 16)
- Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Total Score at Week 16(Baseline, Week 16)
- Percentage of Participants With Assessment of SpondyloArthritis International Society 20% Response Criteria (ASAS20) Response at Week 16(Week 16)
- Percentage of Participants With Assessment of SpondyloArthritis International Society (ASAS) Partial Remission (PR) at Week 16(Week 16)
- Percentage of Participants With Ankylosing Spondylitis Disease Activity Score Major Improvement (ASDAS-MI) at Week 16(Week 16)
- Percentage of Participants With Assessment of SpondyloArthritis International Society (ASAS) 5/6 Response at Week 16(Week 16)
- Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 16(Baseline, Week 16)
- Change From Baseline in Nocturnal Spinal Pain Score Using Numeric Rating Scale (NRS) at Week 16(Baseline, Week 16)
- Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Total Score at Week 16(Baseline, Week 16)
- Change From Baseline in the Short Form 36-Item Health Survey (SF-36) Physical Component Summary (PCS) Score at Week 16(Baseline, Week 16)
- Change From Baseline in Bath Ankylosing Spondylitis Disease Metrology Index (BASMI) at Week 16(Baseline, Week 16)
- Change From Baseline in the Maastricht Ankylosing Spondylitis Enthesitis (MASES) Index in the Subgroup of Participants With Enthesitis at Baseline at Week 16(Baseline, Week 16)
- Percentage of Participants With Enthesitis-free State at Week 16 Based on the Maastricht Ankylosing Spondylitis Enthesitis (MASES) Index in the Subgroup of Participants With Enthesitis at Baseline(Baseline, Week 16)
- Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the Study(From Baseline (Day 1) until Safety-Follow-Up (up to Week 68) (Week 48 last IMP intake + 20 weeks SFU))
- Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the Study(From Baseline (Day 1) until Safety Follow-Up (up to Week 68))
- Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal From Investigational Medicinal Product (IMP) During the Study(From Baseline (Day 1) until Safety-Follow-Up (up to Week 68))