Phase 3 Randomized, Double-Blind, Active Comparator, Placebo-Controlled Study Of The Efficacy And Safety Of 2 Doses Of CP 690,550 In Patients With Active Rheumatoid Arthritis On Background Methotrexate
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 717
- 试验地点
- 1
- 主要终点
- Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Month 6
研究概览
简要总结
This is a comparative study of CP 690,550, Humira (adalimumab) and placebo on background methotrexate in patients with Rheumatoid Arthritis. The study is intended to provide evidence of the efficacy and safety of CP 690,550 when dosed 5 mg and 10 mg twice a day on background methotrexate in adult patients with moderate to severe Rheumatoid Arthritis. It is intended to confirm the benefits of CP-690,550 in improving signs and symptoms and physical function that were observed in Rheumatoid Arthritis. An active comparator, adalimumab, is also included.
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
- •The patient has a diagnosis of RA based upon the American College of Rheumatology (ACR) 1987 Revised Criteria.
- •The patient must have had an inadequate response to methotrexate and have active disease, as defined by both: ≥6 joints tender or painful on motion; and ≥6 joints swollen; and fulfills 1 of the following 2 criteria at Screening: 1.ESR (Westergren method) >28 mm in the local laboratory.
- •CRP >7 mg/L in the central laboratory.
- •No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis.
- •The patient must have been on a stable dose of 7.5 mg to 25 mg weekly of methotrexate and washed out of all other DMARDs.
排除标准
- •Blood dyscrasias including confirmed:
- •Hemoglobin <9 g/dL or Hematocrit <30%;
- •White blood cell count <3,000 cu.mm. Absolute neutrophil count <1,200 cu.mm;
- •Platelet count <100,000/L
- •History of any other autoimmune rheumatic disease other than Sjogren's syndrome
- •No malignancy or history of malignancy.
- •History of infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator, within the 6 months prior to the first dose of study drug
- •Patients who have failed any TNFi for either lack of efficacy or a TNFi mechanism related adverse event.
- •Patients who have previously received adalimumab therapy for any reason.
- •Patients who are contraindicated for treatment with adalimumab in accordance with the approved local label.
- •Patients meeting the New York Heart Association Class III and Class IV Congestive Heart failure
研究组 & 干预措施
10 mg
干预措施: CP-690,550 (Drug)
Placebo Sequence 1
干预措施: Placebo (Other)
Placebo Sequence 2
干预措施: Placebo (Other)
adalimumab
干预措施: Biologic TNFi (Biological)
5mg
干预措施: CP 690,550 (Drug)
结局指标
主要结局
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Month 6
时间窗: Month 6
ACR20 response: greater than or equal to (\>=) 20% improvement in tender joint count (TJC); \>= 20% improvement in swollen joint count (SJC); and \>= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP). For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 6 analysis.
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Month 3
时间窗: Baseline, Month 3
HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as sum of domain scores and divided by number of domains answered. Total possible score range 0-3: 0=least difficulty and 3=extreme difficulty. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 3 analysis.
Percentage of Participants With Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) Less Than 2.6 at Month 6
时间窗: Month 6
DAS28-4 (ESR) calculated from SJC and TJC using 28-joint count, erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PtGA) of disease activity (transformed score ranging 0 to 10; higher score indicated greater affectation due to disease activity). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) less than or equal to (\<=) 3.2 implied low disease activity and \> 3.2 to 5.1 implied moderate to high disease activity, and \< 2.6 = remission. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 6 analysis.
次要结局
- Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Month 1 and 3(Month 1, 3)
- Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Month 9 and 12(Month 9, 12)
- Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Month 1, 3 and 6(Month 1, 3, 6)
- Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Month 9 and 12(Month 9, 12)
- Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Month 1, 3 and 6(Month 1, 3, 6)
- Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Month 9 and 12(Month 9, 12)
- Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Baseline, Month 1, 3 and 6(Baseline, Month 1, 3, 6)
- Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Month 9 and 12(Month 9, 12)
- Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Baseline, Month 1, 3 and 6(Baseline, Month 1, 3, 6)
- Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Month 9 and 12(Month 9, 12)
- Disease Activity Score Using 28-Joint Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP])(Baseline, Month 1, 3, 6, 9, 12)
- Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR])(Baseline, Month 1, 3, 6, 9, 12)
- Health Assessment Questionnaire-Disability Index (HAQ-DI) at Month 1, 3 and 6(Month 1, 3, 6)
- Health Assessment Questionnaire-Disability Index (HAQ-DI) at Month 9 and 12(Month 9, 12)
- Patient Assessment of Arthritis Pain at Baseline, Month 1, 3 and 6(Baseline, Month 1, 3, 6)
- Patient Assessment of Arthritis Pain at Month 9 and 12(Month 9, 12)
- Patient Global Assessment (PtGA) of Arthritis Pain at Baseline, Month 1, 3 and 6(Baseline, Month 1, 3, 6)
- Patient Global Assessment (PtGA) of Arthritis Pain at Month 9 and 12(Month 9, 12)
- Physician Global Assessment (PGA) of Arthritis Pain at Baseline, Month 1, 3 and 6(Baseline, Month 1, 3, 6)
- Physician Global Assessment (PGA) of Arthritis Pain at Month 9 and 12(Month 9, 12)
- 36-Item Short-Form Health Survey (SF-36) at Baseline, Month 1, 3 and 6(Baseline, Month 1, 3, 6)
- 36-Item Short-Form Health Survey (SF-36) at Month 9 and 12(Month 9, 12)
- Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT)-Fatigue Scale at Baseline, Month 1, 3 and 6(Baseline, Month 1, 3, 6)
- Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT)-Fatigue Scale at Month 12(Month 12)
- Medical Outcomes Study-Sleep Scale (MOS-SS) at Baseline, Month 1, 3 and 6(Baseline, Month 1, 3, 6)
- Medical Outcomes Study-Sleep Scale (MOS-SS) at Month 12(Month 12)
- Number of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) at Baseline, Month 1, 3 and 6(Baseline, Month 1, 3, 6)
- Number of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) at Month 12(Month 12)
- Euro Quality of Life-5 Dimension (EQ-5D) Health State Profile Utility Score at Baseline, Month 1, 3 and 6(Baseline, Month 1, 3, 6)
- Euro Quality of Life-5 Dimension (EQ-5D) Health State Profile Utility Score at Month 12(Month 12)
- Work Limitations Questionnaire (WLQ) Score at Month 3 and 6(Month 3, 6)
- Work Limitations Questionnaire (WLQ) Score at Baseline and Month 12(Baseline, Month 12)
- Work Productivity and Healthcare Resource Utilization (HCRU) at Baseline, Month 3 and 6(Baseline, Month 3, 6)
- Work Productivity and Healthcare Resource Utilization (HCRU) at Month 12(Month 12)
- Number of Events Including Visits, Surgeries, Tests or Devices as Assessed Using RA-HCRU at Baseline, Month 3 and 6(Baseline, Month 3, 6)
- Number of Events Including Visits, Surgeries, Tests or Devices as Assessed Using RA-HCRU at Month 12(Month 12)
- Number of Days as Assessed Using RA-HCRU at Baseline, Month 3 and 6(Baseline, Month 3, 6)
- Number of Days as Assessed Using RA-HCRU at Month 12(Month 12)
- Number of Hours Per Day as Assessed RA-HCRU at Baseline, Month 3 and 6(Baseline, Month 3, 6)
- Number of Hours Per Day as Assessed RA-HCRU at Month 12(Month 12)
- Work Performance in Past 3 Months on Days Bothered as Assessed Using RA-HCRU at Baseline, Month 3 and 6(Baseline, Month 3, 6)
- Work Performance in Past 3 Months on Days Bothered as Assessed Using RA-HCRU at Month 12(Month 12)