A Multicenter, Phase 2B, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study to Evaluate the Efficacy and Safety of Bimekizumab in Subjects With Active Ankylosing Spondylitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 303
- 试验地点
- 74
- 主要终点
- Percentage of Participants With Axial Spondyloarthritis International Society 40% Response Criteria (ASAS40) at Week 12
研究概览
简要总结
This is a study to evaluate the efficacy and safety of different doses of bimekizumab in subjects with active Ankylosing Spondylitis (AS).
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
- •Subject has active ankylosing spondylitis (AS), determined by documented radiologic evidence fulfilling the Modified New York criteria for AS including symptoms for >=3 months and age of onset <45 years
- •Subject has moderate to severe active disease as defined by each of the following:
- •BASDAI score >=4
- •Spinal pain >=4 on a 0 to 10 NRS (Numeric Rating Scale; from BASDAI item 2)
- •Subjects must have at least 1 of the following:
- •inadequate response to nonsteroidal anti-inflammatory drug (NSAID) therapy
- •intolerance to administration of at least 1 NSAID
- •contraindication(s) to NSAID therapy
- •Subjects who are regularly taking NSAIDs/COX-2 inhibitors as part of their AS therapy are required to be on a stable dose for at least 14 days before Baseline
- •Subjects taking corticosteroids must be on an average daily dose of <=10mg/day prednisone or equivalent for at least 14 days before Baseline and should remain on a stable dose up to Week 16
- •Subjects taking methotrexate (MTX) (<=25mg/week) are allowed to continue their medication if started at least 12 weeks prior to Baseline, with a stable dose for at least 8 weeks before randomization
- •Subjects taking sulfasalazine (up to 3grams/day) or hydroxychloroquine (up to 400mg per day total) are allowed to continue their medication if started at least 12 weeks prior to Baseline, with a stable dose for at least 8 weeks before randomization
- •Subjects may be tumor necrosis factor (TNF) inhibitor-naïve or may have received 1 prior TNF inhibitor. Subjects who have been on a TNF inhibitor previously must have:
- •experienced an inadequate response to previous treatment given for at least 12 weeks
- •been intolerant to administration (eg, had a side effect/adverse event that led to discontinuation)
- •lost access to TNF inhibitor for other reasons
排除标准
- •Subjects with a total ankylosis of the spine, or a diagnosis of any other inflammatory arthritis eg, rheumatoid arthritis (RA), sarcoidosis, systemic lupus erythematosus, or reactive arthritis
- •Subjects with any current sign or symptom that may indicate an active infection (except for the common cold)
- •Subjects with a history of chronic or recurrent infections, or a serious or life-threatening infection within the 6 months prior to the Baseline Visit
- •Subjects receiving any live vaccination within the 8 weeks prior to Baseline
- •Subjects with known tuberculosis (TB) infection, at high risk of acquiring TB infection, with latent TB infection or current or history of nontuberculous mycobacteria (NTMB) infection
- •Subjects with concurrent malignancy or a history of malignancy during the past 5 years will be excluded, with following exceptions that may be included:
- •<= 3 excised or ablated basal cell carcinomas of the skin
- •One squamous cell carcinoma of the skin (stage T1 maximum) successfully excised, or ablated only (other treatments, ie, chemotherapy, do not apply), with no signs of recurrence or metastases for more than 2 years prior to Screening
- •Actinic keratosis (-es)
- •Squamous cell carcinoma-in-situ of the skin successfully excised, or ablated, more than 6 months prior to Screening
研究组 & 干预措施
Placebo
Subjects will receive for 12 Weeks Placebo and will then be re-randomized to Bimekizumab Dose 3 or Bimekizumab Dose 4 for 36 Weeks.
干预措施: Placebo (Other)
Bimekizumab Dose 1
Subjects will receive for 12 Weeks Bimekizumab Dose 1 and will then be re-randomized to Bimekizumab Dose 3 or Bimekizumab Dose 4 for 36 Weeks.
干预措施: Bimekizumab (Drug)
Bimekizumab Dose 2
Subjects will receive for 12 Weeks Bimekizumab Dose 2 and will then be re-randomized to Bimekizumab Dose 3 or Bimekizumab Dose 4 for 36 Weeks.
干预措施: Bimekizumab (Drug)
Bimekizumab Dose 3
Subjects will receive for 48 Weeks Bimekizumab Dose 3.
干预措施: Bimekizumab (Drug)
Bimekizumab Dose 4
Subjects will receive for 48 Weeks Bimekizumab Dose 4.
干预措施: Bimekizumab (Drug)
结局指标
主要结局
Percentage of Participants With Axial Spondyloarthritis International Society 40% Response Criteria (ASAS40) at Week 12
时间窗: Week 12
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 score), 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. Note: Participants with missing data or who discontinue study treatment prior to Week 12 were counted as non-responders.
次要结局
- Change From Baseline in Ankylosing Spondylitis Disease Activity Score - C-Reactive Protein (ASDAS [CRP]) at Week 12(From Baseline to Week 12)
- Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Functional Index (BASFI)(From Baseline to Week 12)
- Percentage of Participants With Axial Spondyloarthritis International Society 20% Response Criteria (ASAS20) at Week 12(Week 12)
- Percentage of Participants With Axial Spondyloarthritis International Society (ASAS) 5/6 Response at Week 12(Week 12)
- Percentage of Participants With at Least One Adverse Event (AE) During the Study(From Screening until Safety Follow-Up Visit (up to Week 77))
- Percentage of Participants With at Least One Serious Adverse Event (SAE) During the Study(From Screening until Safety Follow-Up Visit (up to Week 77))
- Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)(From Baseline to Week 12)
- Percentage of Participants Who Withdrew Due to an Adverse Event (AE) During the Study(From Screening until Safety Follow-Up Visit (up to Week 77))