Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of Certolizumab Pegol in Subjects With Active Axial Spondyloarthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 325
- 试验地点
- 104
- 主要终点
- Assessment in Axial Spondyloarthritis International Society 20 % (ASAS20) Response Criteria at Week 12
研究概览
简要总结
The study is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of two dose regimens of Certolizumab Pegol (CZP) in subjects with active axial Spondyloarthritis (axial SpA).
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
- •Documented diagnosis of adult-onset axial Spondyloarthritis (SpA) of at least 3 months' duration as defined by the specified Assessment of Spondyloarthritis International Society (ASAS) criteria
- •Active disease as defined by:
- •Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4
- •Back pain ≥ 4 on a 0 to 10 Neurobehavioral Rating Scale (NRS) (from BASDAI item 2)
- •C-Reactive Protein (CRP) > ULN (Upper Limit of Normal) and/or current evidence (ie, within the last 3 months from Screening) for Sacroiliitis on Magnetic Resonance Imaging (MRI) as defined by Assessment of Spondyloarthritis International Society (ASAS) criteria
- •Intolerance to or inadequate response to at least 1 Nonsteroidal Anti-Inflammatory Drug (NSAID)
排除标准
- •Presence of total Spinal Ankylosis ("bamboo spine")
- •Diagnosis of any other Inflammatory Arthritis
- •Prior treatment with any experimental biological agents for treatment of Axial Spondyloarthritis (SpA)
- •Exposure to more than 1 TNF-antagonist or to more than 2 previous biological agents for Axial Spondyloarthritis (SpA)
- •History of or current chronic or recurrent infections
- •High risk of infection
- •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
研究组 & 干预措施
CZP 200 mg Q2W
Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards.
At every visit, subjects received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind.
干预措施: CZP 200 mg Q2W (Biological)
CZP 200 mg Q2W
Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards.
At every visit, subjects received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind.
干预措施: Placebo (Other)
CZP 400 mg Q4W
Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 8 onwards.
Subjects received 2 injections of Placebo every 4 weeks in between the 2 injections of 200 mg CZP to maintain the study blind.
干预措施: CZP 400 mg Q4W (Biological)
CZP 400 mg Q4W
Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 8 onwards.
Subjects received 2 injections of Placebo every 4 weeks in between the 2 injections of 200 mg CZP to maintain the study blind.
干预措施: Placebo (Other)
Placebo
Matching Placebo to CZP injections from Week 0 to Week 24. Placebo subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group on Week 16.
After 24 weeks, all subjects were randomized to active treatment with CZP 200 mg Q2W or CZP 400 mg Q4W.
干预措施: Placebo (Other)
Placebo to CZP 200 mg escape on Week 16
Matching Placebo to CZP injections from Week 0 to Week 16. Subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group on Week 16 and were treated with three loading doses of CZP 400 mg sc on Weeks 16, 18 and 20, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 22 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind.
干预措施: CZP 200 mg Q2W (Biological)
Placebo to CZP 200 mg escape on Week 16
Matching Placebo to CZP injections from Week 0 to Week 16. Subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group on Week 16 and were treated with three loading doses of CZP 400 mg sc on Weeks 16, 18 and 20, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 22 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind.
干预措施: Placebo (Other)
Placebo to CZP 400 mg escape on Week 16
Matching Placebo to CZP injections from Week 0 to Week 16. Subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group on Week 16 and were treated with three loading doses of CZP 400 mg sc on Weeks 16, 18 and 20, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 24 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind.
干预措施: CZP 400 mg Q4W (Biological)
Placebo to CZP 400 mg escape on Week 16
Matching Placebo to CZP injections from Week 0 to Week 16. Subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group on Week 16 and were treated with three loading doses of CZP 400 mg sc on Weeks 16, 18 and 20, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 24 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind.
干预措施: Placebo (Other)
Placebo to CZP 200 mg on Week 24
Matching Placebo to CZP injections from Week 0 to Week 24. Three loading doses of CZP 400 mg sc were given on Weeks 24, 26 and 28, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 30 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind.
干预措施: CZP 200 mg Q2W (Biological)
Placebo to CZP 200 mg on Week 24
Matching Placebo to CZP injections from Week 0 to Week 24. Three loading doses of CZP 400 mg sc were given on Weeks 24, 26 and 28, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 30 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind.
干预措施: Placebo (Other)
Placebo to CZP 400 mg on Week 24
Matching Placebo to CZP injections from Week 0 to Week 24. Three loading doses of CZP 400 mg sc were given on Weeks 24, 26 and 28, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 32 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind.
干预措施: CZP 400 mg Q4W (Biological)
Placebo to CZP 400 mg on Week 24
Matching Placebo to CZP injections from Week 0 to Week 24. Three loading doses of CZP 400 mg sc were given on Weeks 24, 26 and 28, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 32 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind.
干预措施: Placebo (Other)
结局指标
主要结局
Assessment in Axial Spondyloarthritis International Society 20 % (ASAS20) Response Criteria at Week 12
时间窗: Week 12
The ASAS20 is defined as an improvement of at least 20 % and absolute improvement of at least 1 unit on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 following domains: * Patient's Global Assessment of Disease Activity * Pain assessment (total spinal pain) * Function (represented by Bath Ankylosing Spondylitis Functional Index (BASFI)) * Inflammation (the mean of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and absence of deterioration in the potential remaining domain (deterioration is defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit).
次要结局
- Change From Baseline in the Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 12(From Baseline to Week 12)
- Change From Baseline in Sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Week 12(From Baseline to Week 12)
- Assessment in Axial Spondyloarthritis International Society 20 % (ASAS20) Response Criteria at Week 24(Week 24)
- Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24(From Baseline to Week 24)
- Change From Baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24(From Baseline to Week 24)
- Change From Baseline in the Spine Ankylosing Spondylitis Spine Magnetic Resonance Imaging (MRI) Scoring System for Disease Activity (ASspiMRI-a) in the Berlin Modification at Week 12(From Baseline to Week 12)
- Change From Baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 12(From Baseline to Week 12)
- Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 12(From Baseline to Week 12)
- Change From Baseline in the Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 24(From Baseline to Week 24)