A Multicenter, Single-blind, Randomized Parallel-group Study to Assess the Short- and Long-term Efficacy of Certolizumab Pegol Plus Methotrexate Compared to Adalimumab Plus Methotrexate in Subjects With Moderate to Severe Rheumatoid Arthritis Responding Inadequately to Methotrexate
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 915
- 试验地点
- 175
- 主要终点
- Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 12
研究概览
简要总结
This study is conducted to evaluate the short (12 Weeks) and long term (104 Weeks) efficacy of Certolizumab Pegol compared with Adalimumab both in combination with Methotrexate (MTX) in the treatment of moderate to severe Rheumatoid Arthritis (RA) that is not responding adequately to MTX.
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
- Single (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
- •Subject must have a diagnosis of Rheumatoid Arthritis (RA) at Screening, as defined by the 2010 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria (Aletaha D et al, 2010)
- •Subject must have a positive Rheumatoid Factor (RF) and/or a positive anti-Cyclic Citrullinated Peptide antibody (anti-CCP) as determined by the central laboratory at Screening
- •Subject must have moderate to severe RA disease at Screening and Baseline defined as:
- •Screening (all criteria required)
- •≥ 4 swollen joints (of 28 prespecified joints)
- •Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) > 3.2
- •C-Reactive Protein (CRP) concentration ≥ 10 mg/L (or 1.0 mg/dL) or Erythrocyte Sedimentation Rate (ESR) (Westergren) ≥ 28 mm/hr
- •Baseline (both criteria required)
- •≥ 4 swollen joints (of 28 prespecified joints)
- •Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) > 3.2
- •Subject must have inadequately responded previously to Methotrexate (MTX)
- •Subject is using MTX 15 to 25 mg/week orally or subcutaneously at Screening and has used the same MTX regimen for a minimum of 28 days prior to Baseline
排除标准
- •Subject has previously received any biological Disease Modifying Antirheumatic Drug (DMARD) or has received treatment with cyclophosphamide, chlorambucil, Janus Kinase, phosphodiesterase 4 inhibitors or investigational agents such as spleen tyrosine kinase
- •Diagnosis of any other inflammatory arthritis
- •Infected with Tuberculosis (TB) or high risk of acquiring TB infection
- •Subjects with concurrent acute or chronic viral hepatitis B or C infection
- •Subjects with a history of chronic or recurrent infections or subjects at high risk of infection
- •Use of prohibited medications like nonbiological DMARDs (excluding MTX), biological DMARDs excluding study medications, experimental therapy, IA hyaluronic acid
研究组 & 干预措施
Certolizumab Pegol + Methotrexate (CZP + MTX)
干预措施: Certolizumab Pegol (CZP) (Biological)
Certolizumab Pegol + Methotrexate (CZP + MTX)
干预措施: Methotrexate (MTX) (Drug)
Adalimumab + Methotrexate (ADA + MTX)
干预措施: Adalimumab (ADA) (Biological)
Adalimumab + Methotrexate (ADA + MTX)
干预措施: Methotrexate (MTX) (Drug)
CZP + MTX followed by ADA + MTX
Those subjects who received Certolizumab Pegol (400 mg at Weeks 0, 2, 4 followed by 200 mg every two weeks) + Methotrexate (CZP+ MTX) at Baseline and are Non-Responders at Week 12, switch to Adalimumab (40 mg) + Methotrexate (ADA + MTX) after Week 12.
干预措施: Certolizumab Pegol (CZP) (Biological)
CZP + MTX followed by ADA + MTX
Those subjects who received Certolizumab Pegol (400 mg at Weeks 0, 2, 4 followed by 200 mg every two weeks) + Methotrexate (CZP+ MTX) at Baseline and are Non-Responders at Week 12, switch to Adalimumab (40 mg) + Methotrexate (ADA + MTX) after Week 12.
干预措施: Adalimumab (ADA) (Biological)
CZP + MTX followed by ADA + MTX
Those subjects who received Certolizumab Pegol (400 mg at Weeks 0, 2, 4 followed by 200 mg every two weeks) + Methotrexate (CZP+ MTX) at Baseline and are Non-Responders at Week 12, switch to Adalimumab (40 mg) + Methotrexate (ADA + MTX) after Week 12.
干预措施: Methotrexate (MTX) (Drug)
ADA + MTX followed by CZP + MTX
Those subjects who received Adalimumab (40 mg + Placebo at Weeks 0, 2, 4 followed by 40 mg ADA every two weeks) + Methotrexate (ADA+ MTX) at Baseline and are Non-Responders at Week 12, switch to Certolizumab Pegol (400 mg at Weeks 12, 14, 16 followed by 200 mg every two weeks) + Methotrexate (CZP+ MTX) after Week 12.
干预措施: Certolizumab Pegol (CZP) (Biological)
ADA + MTX followed by CZP + MTX
Those subjects who received Adalimumab (40 mg + Placebo at Weeks 0, 2, 4 followed by 40 mg ADA every two weeks) + Methotrexate (ADA+ MTX) at Baseline and are Non-Responders at Week 12, switch to Certolizumab Pegol (400 mg at Weeks 12, 14, 16 followed by 200 mg every two weeks) + Methotrexate (CZP+ MTX) after Week 12.
干预措施: Adalimumab (ADA) (Biological)
ADA + MTX followed by CZP + MTX
Those subjects who received Adalimumab (40 mg + Placebo at Weeks 0, 2, 4 followed by 40 mg ADA every two weeks) + Methotrexate (ADA+ MTX) at Baseline and are Non-Responders at Week 12, switch to Certolizumab Pegol (400 mg at Weeks 12, 14, 16 followed by 200 mg every two weeks) + Methotrexate (CZP+ MTX) after Week 12.
干预措施: Methotrexate (MTX) (Drug)
结局指标
主要结局
Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 12
时间窗: Week 12
Subjects who met the ACR20 criteria were those subjects with at least 20% improvement from Baseline for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS).
Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104
时间窗: Week 104
DAS28 \[ESR\] was calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC), Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula: 0.56 x √ (TJC) + 0.28 x √ (SJC) + 0.70 x lognat (ESR) + 0.014 x Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity.
次要结局
- Percentage of Week 12 Responders Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104(Week 104)
- Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 6(Week 6)
- Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 6(Week 6)
- Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 12(Week 12)
- Percentage of Subjects With a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104, in Subjects Responding at Both Week 6 and Week 12(Week 104)
- Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 104(From Baseline to Week 104)
- Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12(From Week 12 up to Week 104)