A Randomized, Double-blind, Placebo- and Active-controlled Study of Secukinumab to Demonstrate the Efficacy at 24 Weeks and to Assess the Safety, Tolerability and Long Term Efficacy up to 1 Year in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Anti-TNFα Agents (CAIN457F2309) and A Four Year Extension Study to Evaluate the Long Term Efficacy, Safety and Tolerability of Secukinumab in Patients With Active Rheumatoid Arthritis (CAIN457F2309E1)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 551
- 试验地点
- 118
- 主要终点
- Percentage of Participants Achieving an American College of Rheumatology Response 20 (ACR20).
研究概览
简要总结
The core and extension studies assessed the safety and efficacy of secukinumab when added to a background therapy in patients with active rheumatoid arthritis who are intolerant to or have had an inadequate response to anti-TNF-α agents. Patients received either secukinumab, placebo or abatacept (active comparator). The core study was completed. However, the extension study was prematurely terminated after the primary endpoint analysis of the core study at week 24 had demonstrated numerically higher efficacy for the active comparator abatacept compared to secukinumab.
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
- •Male or non-pregnant, non-lactating female patients
- •Presence of RA classified by ACR 2010 revised criteria for at least 3 months before screening
- •At Baseline: Disease activity criteria defined by >= 6 tender joints out of 68 and >= 6 swollen joints out of 66
- •WITH at least 1 of the following at screening:
- •Anti-Cyclic Citrullinated Peptide (Anti-CCP) antibodies positive OR
- •Rheumatoid Factor positive
- •AND WITH at least 1 of the following at screening:
- •High sensitivity C-Reactive Protein (hsCRP) >= 10 mg/L OR
- •Erythrocyte Sedimentation Rate (ESR) >= 28 millimeter (mm)/1st hour
- •Patients must have been taking at least one anti-TNF-α agent given at an approved dose for at least 3 months before randomization and have experienced an inadequate response to treatment or have been intolerant to at least one administration of an anti-TNF-α agent
- •Patients must be taking MTX or any other DMARD (but not more than 1 DMARD) for at least 3 months before randomization and have to be on a stable dose at least 4 weeks before randomization (7.5 to 25 mg/week for MTX or other DMARD at maximum tolerated dose)
排除标准
- •Chest x-ray with evidence of ongoing infectious or malignant process, obtained within 3 months prior to screening and evaluated by a qualified physician
- •RA patients functional status class IV according to the ACR 1991 revised criteria
- •Patients who have ever received biologic immunomodulating agents except for those targeting TNFα
- •Previous treatment with any cell-depleting therapies
- •Other protocol-defined inclusion/exclusion criteria may apply.
结局指标
主要结局
Percentage of Participants Achieving an American College of Rheumatology Response 20 (ACR20).
时间窗: week 24
ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire \[HAQ-DI\] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR). The ACR20 response results at week 24 used non-responder imputation.
次要结局
- Change From Baseline in HAQ-DI - Using Mixed Model Repeated Measures (MMRM)(baseline, weeks 1, 2, 4, 8, 12, 16, 20 and 24)
- Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP)(baseline, week 24)
- Change From Baseline in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI)(baseline, week 24)
- Percentage of Participants Achieving ACR50(week 24)
- Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation(baseline, weeks 1, 2, 4, 8, 12, 16, 20 and 24)
- Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data(baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52)
- Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Observed Data(baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52)
- Change From Baseline in hsCRP - Observed Data(baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52)
- Change From Baseline in Erythrocyte Sedimentation Rate (ESR) - Observed Data(baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52)
- Change From Baseline in HAQ-DI - Observed Data(baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52)
- Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Using MMRM(baseline, weeks 1, 2, 4, 8, 12, 16, 20 and 24)