A Randomized, Double-blind, Parallel Group Placebo-controlled Study of the Safety and Reduction of Signs and Symptoms During Treatment With Tocilizumab (TCZ) Versus Placebo in Patients With Ankylosing Spondylitis Who Have Had an Inadequate Response to Previous TNF Antagonist Therapy
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 113
- 主要终点
- Percentage of ASsessment in Ankylosing Spondylitis 20 (ASAS20) Responders at Week 12
研究概览
简要总结
This randomized, double-blind, placebo-controlled study evaluated the safety and efficacy of tocilizumab (RoActemra/Actemra) in patients with ankylosing spondylitis (AS) who had an inadequate response to previous tumor necrosis factor (TNF) antagonist therapy. Patients were randomized to receive tocilizumab at a dose of either 8 mg/kg or 4 mg/kg intravenously (iv) or placebo every 4 weeks for 24 weeks. The double-blind treatment period was followed by open-label treatment with tocilizumab 8 mg/kg iv every 4 weeks until Week 104 for all patients.
This study and all further clinical development of tocilizumab AS was halted after a review of 12-week data from Study NA22823, a randomized double-blind, placebo-controlled study in TNF antagonist naïve AS patients, failed to demonstrate efficacy.
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
- •Adult patients ≥ 18 years of age.
- •Ankylosing spondylitis as defined by the modified New York criteria for ≥ 3 months prior to baseline.
- •Active disease at screening and baseline (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] ≥ 4.0, spinal pain visual analog scale [VAS] ≥ 40).
- •Inadequate response or intolerant to 1 or more previous non-steroidal anti-inflammatory drugs (NSAIDs).
- •Inadequate response to treatment with etanercept, infliximab, adalimumab, or golimumab because of inadequate efficacy.
- •Tumor necrosis factor (TNF) antagonist therapy must have been discontinued at least 8 weeks prior to baseline (etanercept 4 weeks).
- •Traditional disease-modifying anti-rheumatic drugs (DMARDs) must be withdrawn for at least 4 weeks prior to baseline (methotrexate, sulfasalazine, and hydroxychloroquine or chloroquine may be allowed if at stable dose for at least 4 weeks prior to baseline).
- •Oral corticosteroids (≥ 10 mg/day prednisone or equivalent) and NSAIDs/cyclooxygenase-2 [COX-2] inhibitors must be at stable dose for at least 4 weeks prior to baseline.
排除标准
- •Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months after randomization.
- •Total ankylosis of spine (as determined by investigator).
- •Inflammatory rheumatic disease other than ankylosing spondylitis.
- •Active, acute uveitis at baseline.
- •Previous treatment with tocilizumab.
- •Intra-articular or tendon injections or parenteral corticosteroids within 4 weeks prior to screening.
- •History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
- •Active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infection.
- •History of or currently active primary or secondary immunodeficiency.
- •Body weight > 150 kg.
研究组 & 干预措施
Tocilizumab 4 mg/kg
Patients received tocilizumab 4 mg/kg intravenously every 4 weeks for 24 weeks.
干预措施: Tocilizumab (Drug)
Tocilizumab 8 mg/kg
Patients received tocilizumab 8 mg/kg intravenously every 4 weeks for 24 weeks.
干预措施: Tocilizumab (Drug)
Placebo
Patients received placebo to tocilizumab intravenously every 4 weeks for 24 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of ASsessment in Ankylosing Spondylitis 20 (ASAS20) Responders at Week 12
时间窗: Baseline to Week 12
ASAS20 was defined as an improvement of ≥ 20% and an absolute improvement of ≥ 10 units on a 0-100 visual analog scale (VAS) from Baseline to Week 12 in 3 of 4 domains: 1-Patient global assessment (with extremes labelled none and severe), 2-Pain assessment (average total and nocturnal pain scores with extremes labelled no pain and most severe pain), 3-Function (represented by the Bath Ankylosing Spondylitis (BAS) Functional Index \[BASFI\] average of 10 questions regarding ability to perform specific tasks with extremes labelled easy and impossible), and 4-Inflammation (average of the last 2 questions on the 6-question BAS Disease Activity Index \[BASDAI\] concerning morning stiffness intensity with extremes labelled none and very severe and duration between 0 and 2 or more hours); and the absence of deterioration (of at least 20% and absolute change of at least 10 units on a 0-100 mm scale) in the remaining domain.
次要结局
未报告次要终点