Phase 3, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate Efficacy and Safety of Certolizumab Pegol in Subjects With Active Axial Spondyloarthritis (axSpA) Without X-Ray Evidence of Ankylosing Spondylitis (AS) and Objective Signs of Inflammation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 317
- 试验地点
- 105
- 主要终点
- Certolizumab Pegol Plasma Concentration at Week 12
研究概览
简要总结
Patients with active Axial Spondyloarthritis without x-ray evidence of Ankylosing Spondylitis and with signs of inflammation will be randomly assigned to receive certolizumab pegol (CZP) 200 mg every two weeks or placebo. The primary objective is to demonstrate the efficacy of CZP in these patients.
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
- •At least 18 years old at the start of Screening Visit
- •A documented diagnosis of adult-onset axial SpondyloArthritis (axSpA) and meet the Assessment of SpondyloArthritis International Society (ASAS) criteria for axSpA
- •Subjects must have had back pain for at least 12 months before Screening
- •No sacroiliitis defined by Modified New York (mNY) criteria on sacroiliac (SI) x-rays
- •Active disease at Screening as defined by
- •Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score >= 4
- •Spinal pain >= 4 on a 0 to 10 Numerical Rating Scale (NRS)
- •Inadequate response to, have a contraindication to, or have been intolerant to at least 2 Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
排除标准
- •Diagnosis of AS or any other Inflammatory Arthritis
- •Prior treatment with any experimental biological agents for treatment of Axial SpondyloArthritis (SpA)
- •Exposure to more than 1 tumor necrosis factor (TNF)-antagonist or primary failure to TNF antagonist therapy
- •History of or current chronic or recurrent infections
- •Subjects with known Tuberculosis (TB) infection, at high risk of acquiring TB infection, or latent Tuberculosis (LTB)
- •Recent live vaccination
- •Concurrent malignancy or a history of malignancy
- •Class III or IV congestive heart failure - New York Heart Association (NYHA)
- •Demyelinating disease of the central nervous system
- •Female subjects who are breastfeeding, pregnant or plan to become pregnant during the study or within 3 months following the last dose of the investigational product
- •Subjects with any other condition which, in the investigator's judgment, would make the subject unsuitable for inclusion in the study
结局指标
主要结局
Certolizumab Pegol Plasma Concentration at Week 12
时间窗: Week 12
Certolizumab pegol plasma concentration was measured at Week 12, in µg/mL.
Certolizumab Pegol Plasma Concentration at Baseline
时间窗: Baseline (Week 0)
Certolizumab pegol plasma concentration was measured at Baseline in micrograms per millilitre (µg/mL).
Certolizumab Pegol Plasma Concentration at Week 1
时间窗: Week 1
Certolizumab pegol plasma concentration was measured at Week 1, in µg/mL.
Certolizumab Pegol Plasma Concentration at Week 24
时间窗: Week 24
Certolizumab pegol plasma concentration was measured at Week 24, in µg/mL.
Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 12
时间窗: Week 12
This variable was considered as primary for Canada (and any other country where applicable or where requested by Regulatory Authorities) and as secondary variable in all other countries. The ASAS40 response was defined as relative improvements of at least 40 % and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS), where 0 is "not active" and 10 is "very active" in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain.
Certolizumab Pegol Plasma Concentration at Week 4
时间窗: Week 4
Certolizumab pegol plasma concentration was measured at Week 4, in µg/mL.
Certolizumab Pegol Plasma Concentration at Week 52
时间窗: Week 52
Certolizumab pegol plasma concentration was measured at Week 52, in µg/mL.
Certolizumab Pegol Plasma Concentration at Follow-Up (FU) Visit
时间窗: Follow-up Visit (up to Week 60)
Certolizumab pegol plasma concentration was measured at the Follow-Up Visit, in µg/mL. Follow-Up Visit was defined as 8 weeks after Week 52 or Withdrawal (WD) visit for subjects not participating in the Safety Follow-Up Extension (SFE) Period.
Percentage of Subjects With Ankylosing Spondylitis Disease Activity Score Major Improvement (ASDAS-MI) Response Criteria Response at Week 52
时间窗: Week 52
This variable was considered as primary in all countries except for Canada (and any other country where applicable or where requested by Regulatory Authorities) where it was considered as secondary variable. ASDAS-MI was achieved when there was a reduction (improvement) \>= 2.0 in the ASDAS relative to Baseline, or when the lowest possible ASDAS score (0.6) was reached. The ASDAS was calculated as the sum of the following components: 0.121 × Back pain (BASDAI Q2 result) 0.058 × Duration of morning stiffness (BASDAI Q6 result) 0.110 × Patient's Global Assessment of Disease Activity (PGADA) 0.073 × Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm \[ln\] of the (CRP \[mg/L\] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units, where 0 is "not active" and 10 is "very active").
Certolizumab Pegol Plasma Concentration at Week 2
时间窗: Week 2
Certolizumab pegol plasma concentration was measured at Week 2, in µg/mL.
Certolizumab Pegol Plasma Concentration at Week 36
时间窗: Week 36
Certolizumab pegol plasma concentration was measured at Week 36, in µg/mL.
次要结局
- Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 52(Week 52)
- Change From Baseline in ASQoL at Week 36(From Baseline to Week 36)
- Number of Subjects With Anterior Uveitis (AU) or New AU Flares Through Week 52(Throughout the study conduct (up to Week 52))
- Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Functional Index (BASFI)(From Baseline to Week 52)
- Number of Subjects Without Relevant Changes to Background Medication From Baseline to Week 52(From Baseline to Week 52)
- Change From Baseline in ASQoL at Week 2(From Baseline to Week 2)
- Change From Baseline to Week 12 in Sacroiliac Spondyloarthritis Research Consortium of Canada (SI-SPARCC) Score(From Baseline to Week 12)
- Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 52(From Baseline to Week 52)
- Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Functional Index (BASFI)(From Baseline to Week 12)
- Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)(From Baseline to Week 12)
- Change From Baseline in ASQoL at Week 4(From Baseline to Week 4)
- Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)(From Baseline to Week 52)
- Change From Baseline in ASQoL at Week 1(From Baseline to Week 1)
- Change From Baseline in ASQoL at Week 24(From Baseline to Week 24)
- Change From Baseline in Nocturnal Spinal Pain Numerical Rating Scale (NRS) at Week 52(From Baseline to Week 52)
- Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) During the Study(From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156))
- Change From Baseline in ASQoL at Week 12(From Baseline to Week 12)
- Change From Baseline in ASQoL at Week 48(From Baseline to Week 48)
- Percentage of Subjects With Adverse Events Leading to Withdrawal From Investigational Medicinal Product (IMP) During the Study(From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156))
- Percentage of Subjects With Serious Adverse Events (SAEs) During the Study(From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156))