A Randomized, Open Label Multicenter Trial to Investigate the Efficacy of a Treat-to-target (T2T) Treatment Strategy With Secukinumab (AIN457) as a First-line Biologic Compared to a Standard-of-care (SOC) Treatment Over 36 Weeks in Patients With Active Axial Spondyloarthritis (axSpA)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 304
- 试验地点
- 1
- 主要终点
- Percentage of Patients Achieving an ASAS40 Response at Week 24
研究概览
简要总结
This was a randomized, parallel-group, open-label, multicenter study in patients with active axSpA. The aim of the study was to demonstrate that the efficacy of a T2T approach (with secukinumab as a first-line biologic) was superior to a SOC approach in terms of achieving strong clinical efficacy in patients with active axSpA who were naïve to biological therapy and who had an inadequate response to prior non-steroidal anti-inflammatory drug (NSAID) treatment.
详细描述
The study included an 8-week Screening period, a 36-week treatment period, and a 20-week safety follow-up period. Neither investigators nor patients were blinded. The primary endpoint was the percentage of patients achieving an ASAS40 response at Week 24. At Baseline, patients were randomized equally to one of two treatment groups (T2T or SOC).
Patients were evaluated every 12 weeks from Baseline through to Week 36. Safety evaluations were included in the regular visits; in addition, a safety follow-up visit was performed 20 weeks after the last study visit (i.e. Week 36) and took place at Week 56 for patients completing the study according to the protocol.
Patients assigned to the SOC treatment group received SOC treatment at the discretion of the investigator in accordance with current clinical practice.
Patients assigned to the T2T treatment group received first line biological treatment with secukinumab 150 mg. Responders were defined as those patients with an ASDAS clinically important improvement of ≥ 1.1.
At week 12 responders continued secukinumab 150 mg, whereas treatment was escalated to 300 mg for non-responders.
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
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Axial Spondyloarthritis, axSpA (either Non-Radiographic Axial Spondyloarthritis or Radiographic Axial Spondyloarthritis) fulfilling the Ankylosing Spondyloarthritis International Society classification criteria for axSpA
- •Active disease as defined by having an Ankylosing Spondylitis Disease Activity Score ≥ 2.1 at Screening and Baseline despite concurrent Non-Steroidal Anti-Inflammatory Drug (NSAID) therapy, or intolerance/contraindication to NSAIDs.
- •Objective signs of inflammation at Screening as defined by: Magnetic Resonance Imaging (MRI) of sacroiliac joints performed up to 3 months prior to screening showing acute inflammatory lesion(s), OR elevated quick C-reactive Protein (CRP) (> 5 mg/L), OR MRI showing acute inflammatory lesion(s) in the sacroiliac joints and spine performed during screening period.
- •Inadequate response to NSAIDs
排除标准
- •Previous exposure to secukinumab or other biologic drug directly targeting Interleukin(IL)-17 or IL-17 receptor.
- •Patients who have previously been treated with Tumor Necrosis Factor Alpha inhibitors (investigational or approved).
- •Patients treated with any cell-depleting therapies.
- •Active ongoing inflammatory diseases or underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions, which in the opinion of the investigator immunosuppressed the patient and/or places the patient at unacceptable risk for participation in an immunomodulatory therapy.
- •History of clinically significant liver disease or liver injury
- •History of renal trauma, glomerulonephritis, or patients with one kidney only, or a serum creatinine level exceeding 1.8 mg/dL (159.12 μmol/L).
- •Active systemic infections during the last 2 weeks (exception: common cold) prior to randomization.
- •History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis (TB) infection
- •Patients positive for human immunodeficiency virus, hepatitis B or hepatitis C
- •Life vaccinations within 6 weeks prior to Baseline or planned vaccination during study participation until 12 weeks after last study treatment administration.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
TREAT-TO-TARGET (T2T)
Patients received secukinumab 150 mg subcutaneous (s.c.) weekly until Week 4 (Baseline, Week 1, Week 2, Week 3, Week 4)) and then at Week 8. At Week 12, if ASDAS clinically important improvement was achieved and maintained, patients received treatment up to Week 32 if they maintained the response. If ASDAS clinically important improvement was not achieved, patients received an escalated dose of secukinumab 300 mg s.c. every 4 weeks until Week 20.
At Week 24, patients who were receiving secukinumab 300 mg, and achieved ASDAS clinically important improvement, continued treatment up to Week 32. If patients did not achieve ASDAS clinically important improvement, they were switched to adalimumab biosimilar (Hyrimoz®) 40 mg s.c. every 2 weeks until Week 34.
Each patient was treated for a maximum of 36 weeks (last dose of secukinumab at Week 32, last dose of adalimumab biosimilar (Hyrimoz®) at Week 34).
干预措施: Secukinumab/Adalimumab-Biosimilar (Biological)
Standard-of-care (SOC)
Patients received SOC treatment according to local practice standards by their treating rheumatologist following latest treatment recommendations with NSAIDs as the first-choice drug treatment and disease-modifying anti-rheumatic drugs (DMARDs) for patients with active disease despite the use (or intolerance/contraindication) of NSAIDs.
干预措施: Standard-of-care (Other)
结局指标
主要结局
Percentage of Patients Achieving an ASAS40 Response at Week 24
时间窗: Baseline, Week 24
Assessment of SpondyloArthritis International Society criteria (ASAS) consists of 4 domains measured on visual analog scales (VAS): 1. Patient's global assessment; 2. Patient's assessment of back pain; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). ASAS40 response is defined as an improvement of ≥40% and ≥2 units on a scale of 0 - 10 in at least three of the four ASAS domains and no worsening at all in the remaining domain. A score of 0 indicates less severity; a score of 10 indicates more severity. Percentage was calculated from a logistic regression model: logit(proportion) = treatment + baseline quick C-reactive protein (CRP) + baseline weight.
次要结局
- Percentage of Patients Achieving an ASAS40 Response at Week 12(Baseline, Week 12)
- Percentage of Patients Achieving ASAS20 Response(Baseline, Weeks 12 and 24)
- Percentage of Patients Achieving ASAS Partial Remission(Baseline, Weeks 12 and 24)
- Percentage of Patients Meeting the Ankylosing Spondylitis Disease Activity Score (ASDAS) Definition of Inactive Disease(Baseline, Weeks 12 and 24)
- Percentage of Patients With ASDAS Major Improvement(Baseline, Weeks 12 and 24)
- Percentage of Patients With ASDAS Low Disease Activity(Baseline, Weeks 12 and 24)
- Percentage of Patients Achieving the Bath Ankylosing Spondylitis Disease Activity Index Response 50% (BASDAI 50) at Week 12 and Week 24(Baseline, Weeks 12 and 24)
- Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)(Baseline, Weeks 12 and 24)
- Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)(Baseline, Weeks 12 and 24)
- Change From Baseline in Chest Expansion(Baseline, Weeks 12 and 24)
- Change From Baseline in the ASQoL (Ankylosing Spondylitis Quality of Life Instrument)(Baseline, Weeks 12 and 24)
- Change From Baseline in ASAS-HI (Ankylosing Spondyloarthritis International Society Health Index)(Baseline, Weeks 12 and 24)
- Change From Baseline in Global Disease Assessment (Patient)(Baseline, Weeks 12 and 24)
- Change From Baseline in Global Disease Assessment (Physician)(Baseline, Weeks 12 and 24)