A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of AK111 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
- 125
- 试验地点
- 15
- 主要终点
- Percentage of subjects with treatment-emergent serious adverse events (SAEs) during the study.
研究概览
简要总结
This is a phase 2, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of AK111 in subjects with active ankylosing spondylitis.
详细描述
The purpose of this study is to evaluate the efficacy and safety of AK111 in the treatment of subjects with active ankylosing spondylitis. Subjects will be randomized to receive AK111 or placebo following subcutaneous injection. The study period for each subject will be 25 weeks, including a screening period of up to 35 days, followed by a treatment period of 12 weeks and a follow up period of 8 weeks.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects aged 18-75 years old.
- •Ankylosing spondylitis has been diagnosed for at least 6 months before screening, with radiological evidence that meets the Modified New York Criteria for Ankylosing Spondylitis.
- •Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4 and Spinal pain score≥ 4 (based on BASDAI question 2).
- •Subjects received at least 1 kind of non-steroidal anti-inflammatory drugs (NSAIDs), prior to randomization with an inadequate response or failure to respond.
- •Subjects who are regularly taking NSAIDs, weak opioids or oral glucocorticoids as part of their AS therapy are required to be on a stable dose for at least 14 days before randomization.
- •Subjects taking methotrexate (MTX) (≤25mg/week) or Sulfasalazine (≤3g/day) are allowed to continue their medication if started at least 12 weeks prior to Baseline, with a stable dose for at least 4 weeks before randomization.
排除标准
- •Subjects with total ankylosis of the spine.
- •Subjects with progressive or uncontrolled diseases of respiratory, circulatory, digestive, urogenital, endocrine, nervous or mental systems, or with other chronic diseases that are not suitable to participate to the study.
- •Subjects with other inflammatory diseases or autoimmune diseases except Ankylosing spondylitis (AS).
- •Subjects with any severe systemic or local infection within 2 months before screening.
- •Subjects who are using strong opioid analgesics.
- •Combined use of Disease Modifying Anti-Rheumatic Drugs (DMARDs) other than methotrexate and sulfasalazine, including but not limited to thalidomide, iguratimod, etc. within 4 weeks before randomization.
- •Received any live vaccine within 2 months before screening or planned to receive any live vaccine during the study period.
- •Previous exposure to secukinumab, ixekizumab or any other biologic drug directly targeting IL-17 or IL-17 receptor.
- •Received Natalizumab or other drugs that regulate B cells or T cells within 6 months before screening.
- •Received more than 2 kinds of Tumor necrosis factor alpha(TNF-α) inhibitors before screening.
研究组 & 干预措施
Placebo
Placebo will be administered by subcutaneous injection at Week 0, 1 and 4 , followed by dosing every 4 weeks until Week12.
干预措施: Placebo (Biological)
结局指标
主要结局
Percentage of subjects with treatment-emergent serious adverse events (SAEs) during the study.
时间窗: Baseline to Week20
Percentage of subjects who achieve Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response at Week 16.
时间窗: Week16
ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS has 4 domains: patient global, pain, function (assessed by BASFI) and inflammation (mean of Ankylosing Spondylitis Disease Activity Index \[BASDAI\] question 5 and 6 ). ASAS20 response is defined as improvement of ≥ 20% and ≥1 unit in at least 3 domains (on a scale of 0 \[least\] to 10 \[worst\]) and no worsening of ≥20% and ≥1 unit in the remaining domain.
Percentage of subjects with treatment-emergent adverse events (TEAEs) during the study.
时间窗: Baseline to Week20
次要结局
- Percentage of subjects who achieve ASAS20 response at each visit from baseline.(Baseline to Week 20)
- Percentage of subjects who achieve SpondyloArthritis International Society 40% improvement (ASAS40) response at Week 16.(Week 16)
- Immunogenicity: Number and percentage of subjects with detectable anti-AK111 antibody (ADA).(Baseline to Week 20)
- Terminal elimination half-life (T1/2)(Baseline to Week 20)
- Percentage of subjects who achieve ASAS40 at each visit from baseline.(Baseline to Week 20)
- Change from baseline on the 36-item Short-Form (SF-36) Health Survey at each visit from baseline.(Baseline to Week 20)
- Area under the curve from 0 to the time of the last quantifiable concentration (AUC0-t)(Baseline to Week 20)
- Time of occurrence of Cmax (Tmax)(Baseline to Week 20)
- Change from baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at each visit from baseline.(Baseline to Week 20)
- pharmacodynamics(PD) parameters: Changes of Interleukin-17A (IL-17A) level in peripheral serum compared with baseline and its relationship with AK111 exposure.(Baseline to Week 20)
- Maximum observed concentration (Cmax)(Baseline to Week 20)