A Phase IIIb Open-label run-in Double-blind, Placebo Controlled, Randomized Study to Evaluate the Safety/Efficacy of Certolizumab Pegol Administered Concomitantly With Stable-dose Methotrexate in Patients With Active Rheumatoid Arthritis.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- UCB Pharma
- 入组人数
- 333
- 主要终点
- Percentage of ACR20 (American College of Rheumatology 20% Improvement) Responders at Week 34 in Patients Randomized at Week 18
研究概览
简要总结
During the run-in period, CZP will be administered at 400 mg (2 injections) at Wks 0, 2, and 4 and 200 mg with placebo (1 injection placebo, 1 injection CZP) at Wks 6, 8, 10, 12, 14 and 16. At Wk 18 patients will be grouped as responders or non-responders based on results of the ACR20 at Week 16.
详细描述
Subjects with a stable methotrexate (MTX) dose enter the run-in period in which certolizumab pegol (CZP) will be administered at a dose of 400 mg (2 injections) at Weeks 0, 2, and 4 and at a dose of 200 mg with placebo (1 injection placebo, 1 injection CZP) at Weeks 6, 8, 10, 12, 14 and 16. The dose of MTX should be stable for at least 2 months prior to the Baseline visit and will remain stable throughout the trial, unless there is a need to reduce the dose for reasons of toxicity.
At the Week 18 visit, subjects who were ACR20 (American College of Rheumatology 20% Improvement) responders at Week 16 will be randomized in a double-blinded way to receive either 400 mg CZP given every 4 weeks and placebo given every 4 weeks given as two injections (alternating CZP and placebo every two weeks) plus MTX, 200 mg CZP and placebo administered every 2 weeks (one injection of each) plus MTX, or Placebo administered as two injections every 2 weeks plus MTX. Non-responders will be withdrawn from the study.
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
- •Patients with established adult rheumatoid arthritis currently on Methotrexate for at least 3 months
排除标准
- •All concomitant diseases or pathological conditions that could interfere and impact the assessment of the study treatment
- •Previous clinical trials participation and previous biological therapy that could interfere with the results of the present clinical trial
研究组 & 干预措施
Certolizumab pegol 400 mg and placebo
400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks)
干预措施: Certolizumab pegol (Drug)
Certolizumab pegol 400 mg and placebo
400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks)
干预措施: Placebo (Other)
Certolizumab pegol 200 mg and placebo
200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each)
干预措施: Certolizumab pegol (Drug)
Certolizumab pegol 200 mg and placebo
200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each)
干预措施: Placebo (Other)
Placebo
Placebo administered as two injections every 2 weeks
干预措施: Placebo (Other)
结局指标
主要结局
Percentage of ACR20 (American College of Rheumatology 20% Improvement) Responders at Week 34 in Patients Randomized at Week 18
时间窗: Baseline, Week 34
ACR20 responders are 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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)
次要结局
- Ratio From Baseline in CRP (C-reactive Protein) Level at Week 16 in All Patients(Baseline, Week 16)
- Percentage of ACR50 (American College of Rheumatology 50% Improvement) Responders at Week 34 in Patients Randomized at Week 18(Baseline, Week 34)
- Percentage of ACR70 (American College of Rheumatology 70% Improvement) Responders at Week 34 in Patients Randomized at Week 18(Baseline, Week 34)
- Change From Baseline in DAS28 (Disease Activity Score-28 Items) at Week 34 in Patients Randomized at Week 18(Baseline, Week 34)
- Percentage of ACR20 (American College of Rheumatology 20% Improvement) Responders at Week 16 in All Patients(Baseline, Week 16)
- Percentage of ACR50 (American College of Rheumatology 50% Improvement) Responders at Week 16 in All Patients(Baseline, Week 16)
- Percentage of ACR70 (American College of Rheumatology 70% Improvement) Responders at Week 16 in All Patients(Baseline, Week 16)
- Change From Baseline in DAS28 (Disease Activity Score-28 Items) at Week 16 in All Patients(Baseline, Week 16)
- Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 16 in All Patients(Baseline, Week 16)
- Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 16 in All Patients(Baseline, Week 16)
- SDAI (Simplified Disease Activity Index) Remission (SDAI ≤3.3) at Week 34 in Patients Randomized at Week 18(Week 34)
- CDAI (Clinical Disease Activity Index) Remission (CDAI ≤2.8) at Week 34 in Patients Randomized at Week 18(Week 34)
- DAS28 (Disease Activity Score-28 Items) Remission (DAS28 <2.6) at Week 16 in All Patients(Week 16)
- Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 34 in Patients Randomized at Week 18(Baseline, Week 34)
- Change From Baseline in HAQ-DI (Health Assessment Questionnaire-Disability Index) Score at Week 34 in Patients Randomized at Week 18(Baseline, Week 34)
- Change From Baseline in Fatigue Assessment Scale (FAS) at Week 34 in Patients Randomized at Week 18(Baseline, Week 34)
- Change From Baseline in Physical Functioning (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18(Baseline, Week 34)
- Change From Baseline in Role Physical (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18(Baseline, Week 34)
- SDAI (Simplified Disease Activity Index) Remission (SDAI ≤3.3) at Week 16 in All Patients(Week 16)
- CDAI (Clinical Disease Activity Index) Remission (CDAI ≤2.8) at Week 16 in All Patients(Week 16)
- Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 34 in Patients Randomized at Week 18(Baseline, Week 34)
- Ratio From Baseline in CRP (C-reactive Protein) Level at Week 34 in Patients Randomized at Week 18(Baseline, Week 34)
- Change From Baseline in HAQ-DI (Health Assessment Questionnaire-Disability Index) Score at Week 16 in All Patients(Baseline, Week 16)
- DAS28 (Disease Activity Score-28 Items) Remission (DAS28 <2.6) at Week 34 in Patients Randomized at Week 18(Week 34)
- Change From Baseline in Bodily Pain (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18(Baseline, Week 34)
- Change From Baseline in General Health (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18(Baseline, Week 34)
- Change From Baseline in Vitality (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18(Baseline, Week 34)
- Change From Baseline in Social Functioning (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18(Baseline, Week 34)
- Change From Baseline in Role Emotional (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18(Baseline, Week 34)
- Change From Baseline in Mental Health (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18(Baseline, Week 34)
- Change From Baseline in PCS (Short Form 36-item Health Survey Physical Component Summary) at Week 34 in Patients Randomized at Week 18(Baseline, Week 34)
- Change From Baseline in MCS (Short Form 36-item Health Survey Mental Component Summary) at Week 34 in Patients Randomized at Week 18(Baseline, Week 34)
- Change From Baseline in PAAP (Patient's Assessment of Arthritis Pain) at Week 34 in Patients Randomized at Week 18(Baseline, Week 34)
- Change From Baseline in PtGADA (Patient's Global Assessment of Disease Activity) at Week 34 in Patients Randomized at Week 18(Baseline, Week 34)
- Median Time to Loss of ACR20 (American College of Rheumatology 20% Improvement) Response After Week 18 in Patients Randomized at Week 18.(Week 18 up to Week 34)