A Randomized, Double-blind, Placebo-controlled Multicenter Study of Subcutaneous Secukinumab to Demonstrate Efficacy in the Treatment of Enthesitis at the Achilles Tendon up to 1 Year in Adult Patients With Active Psoriatic Arthritis (PsA) and Axial Spondyloarthritis (axSpA) (ACHILLES)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 204
- 试验地点
- 1
- 主要终点
- Number (%) of Patients With Resolution of Achilles Tendon Enthesitis
研究概览
简要总结
The purpose of this study was to demonstrate efficacy, including effects on inflammation by magnetic resonance imaging (MRI) assessments, of secukinumab on Achilles tendon enthesitis for up to 1 year with a primary focus at Week 24, in patients with active Psoriatic Arthritis and axial Spondyloarthritis despite current or previous non-steroidal anti-inflammatory drugs (NSAID) and/or disease modifying anti-rheumatic drug (DMARD) and/or anti-TNFα therapy.
详细描述
Primary endpoint was at week 24 but there was no interim Clinical Study Report. While Protocol states at chapter 9.7 that a week 24 analysis may be provided (not mandatory as per protocol), all data has been analyzed at week 52.
Some of the secondary endpoints include the whole study period up to week 52 (to address questions on switching placebo to active drug)
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
- •Patients with Psoriatic arthritis: Diagnosis of Psoriatic arthritis as per the Classification criteria for Psoriatic Arthritis (CASPAR criteria) with symptoms for at least 6 months and active Psoriatic arthritis as assessed by ≥ 1 tender joints out of 78 and ≥ 1 swollen joints out of 76 at Baseline (dactylitis of a digit counts as one joint each).
- •Patients with Axial Spondyloarthritis: Diagnosis of Axial Spondyloarthritis as per the classification of the Assessment of Spondyloarthritis International Society axial Spondyloarthritis (ASAS) criteria and objective signs of inflammation at Screening (magnetic resonance imaging (MRI) or definite radiographic sacroilitis and/or abnormal C-Reactive Protein) and active disease assessed by total Bath ankylosing spondylitis disease activity index (BASDAI) ≥ 4 (0-10) at Baseline.
- •Diagnosis of Achilles tendon enthesitis according to swelling and tenderness at the insertional site of the Achilles tendon into the calcaneus.
- •Onset of heel pain ≥ 1 month at Baseline.
- •Heel enthesitis that is magnetic resonance imaging (MRI)-positive according to the investigator's judgement.
- •Patients who have been exposed to up to two TNFα inhibitors.
排除标准
- •Chest X-ray or chest magnetic resonance imaging (MRI) with evidence of ongoing infectious or malignant process.
- •Previous exposure to secukinumab or other biologic drug directly targeting Interleukin (IL)-17 or Interleukin (IL)-17 receptor.
- •Ongoing use of psoriasis treatments / medications (e.g. topical corticosteroids, ultraviolet (UV) therapy) at randomization.
- •Patients who have previously been exposed to more than two Tumor necrosis factor (TNF) inhibitors (investigational or approved).
- •Patients who have ever received biologic immunomodulating agents (investigational or approved), except those targeting Tumor necrosis factor (TNF) inhibitors.
- •Pregnant or nursing (lactating) women.
- •History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection.
研究组 & 干预措施
AIN457/Secukinumab
Secukinumab 150 mg s.c. or Secukinumab 300 mg s.c., respective dose was assigned according to underlying condition, in case of PsA according to severity of concomitant Psoriasis or pre-exposure to anti-TNFα
干预措施: Secukinumab (Biological)
AIN457/Secukinumab Placebo
Secukinumab Placebo s.c.
干预措施: Secukinumab Placebo (Drug)
结局指标
主要结局
Number (%) of Patients With Resolution of Achilles Tendon Enthesitis
时间窗: Week 24
Number (%) of patients with resolution of Achilles tendon enthesitis (affected foot) as assessed by respective subcomponent of Leeds enthesitis index (LEI) at Week 24. The primary analysis was performed via a logistic regression model with the factors treatment, country, and stratification factor diagnosis (PsA or axSpA); patients with a missing assessment were considered as responders if they had already met the response criterion at the time of last assessment.
次要结局
- Mean Change of Heel Pain(Week 24)
- Number (%) of Patients With Resolution of Enthesitis as Assessed by LEI(Week 24)
- Mean Change of Patient's Global Assessment of Disease Activity(Week 24)
- Mean Change of Physician's Assessment of Heel Enthesopathy Activity(Week 24)
- Number (%) of Patients With Improvement of Bone Marrow Edema(Week 24)
- Mean Change of Physician's Global Assessment of Disease Activity(Week 24)
- Mean Change of Heel Pain After Switching From Placebo to Secukinumab(Change from week 24 to week 52)
- Mean Change of Patient's Assessment of Heel Enthesopathy Activity(Week 24)
- Mean Change in Short Form-36 (SF-36) v2(Week 24)
- Percentage of Patients With Resolution of Achilles Tendon Enthesitis After Switching From Placebo to Secukinumab(Weeks 24 and 52)