A RANDOMIZED, DOUBLE-BLIND, STUDY COMPARING THE PHARMACOKINETICS AND PHARMACODYNAMICS, AND ASSESSING THE SAFETY OF PF-05280586 AND RITUXIMAB IN SUBJECTS WITH ACTIVE RHEUMATOID ARTHRITIS ON A BACKGROUND OF METHOTREXATE WHO HAVE HAD AN INADEQUATE RESPONSE TO ONE OR MORE TNF ANTAGONIST THERAPIES
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 220
- 试验地点
- 155
- 主要终点
- AUC 0-inf of Rituximab
研究概览
简要总结
In this study, patients with moderate to severe rheumatoid arthritis who are being treated with methotrexate will receive 2 intravenous treatments with either PF-05280586 or Rituxan (Rituximab) or MabThera (Rituximab). During the course of the study, the effects of the drugs will be assessed by sampling the levels of drug in the blood, blood cell counts, and by comparing these levels among the different treatments. Safety, tolerability and immunologic response also will be evaluated throughout.
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
- •Confirmed diagnosis of rheumatoid arthritis
- •Meets Class I, II or III of the ACR 1991 Revised Criteria
- •RA seropositivity
- •Stable dose of methotrexate
- •Inadequate response to TNF inhibitors
排除标准
- •Any prior treatment with lymphocyte depleting therapies
- •History of active TB infection
- •Known or screen test positive for specific viruses or indicators of viral infection
结局指标
主要结局
AUC 0-inf of Rituximab
时间窗: Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion
The AUC 0-inf refers to the concentration in serum of the drug over time. It represents the total drug exposure over time, from time 0 (the point of drug administration) extrapolated to infinity.
Maximum Serum Concentration (Cmax) of Rituximab
时间窗: Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion
Cmax is the peak serum concentration of study drug (rituximab) after a dose has been administered.
次要结局
- Percentage of Participants With Neutralizing Antibody (NAb) in Participants With a Positive ADA by Visit(Day 1 up to Day 169)
- Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit(Weeks 3, 5, 9, 13, 17, 21 and 25)
- Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit(Weeks 3, 5, 9, 13, 17, 21 and 25 (EOT))
- Duration of B-cell Depletion (τB-cell) (Days)(Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT))
- Percentage of Participants With CD19+ B-cell Count Recovery(Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25)
- Area Under the CD19+ B-cell Count Concentration-time Profile (AUC 0-T, B-cell)(Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT))
- Percentage of Participants by Anti-drug Antibody (ADA) Status(Days 1 up to Day 169.)
- Percent Change From Baseline in HAQ-DI Score by Visit(Baseline, Week 3, 5, 9, 13, 17, 21 and 25)
- Rituximab AUC From Time 0 to 2 Weeks (AUC 0-2wk)(Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion)
- Rituximab AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-T)(Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion)
- Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit(Weeks 3, 5, 9, 13, 17, 21 and 25)
- Percent Change From Baseline in DAS28-CRP by Visit(Baseline and Weeks 3, 5, 9, 13, 17, 21 and 25)
- Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit(Weeks 3, 5, 9, 13, 17, 21 and 25)
- Percentage of Participants With DAS Remission (DAS <2.6) by Visit(Weeks 3, 5, 9, 13, 17, 21 and 25)
- CD19+ B-cell Count AUC From Time 0 to the Last Measurement at Time T (AUC 0-T,B-cell)(Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT))
- Minimum Post-Baseline CD19+ B-cell Count (/uL)(Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT))
- Time to Minimum Post-Baseline CD19+ B-cell Count (Weeks)(Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT))
- Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L])(Baseline and Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21 and 25 (EOT))
- Percent (%) Change From Baseline in Circulating IgM by Visit (g/L)(Baseline and Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21 and 25)
- Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP)(Baseline and Weeks 3, 5, 9, 13, 17, 21 and 25)
- Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit(Weeks 3, 5, 9, 13, 17, 21 and 25)
- Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit(Weeks 3, 5, 9, 13, 17, 21 and 25)
- Percentage of Participants With No EULAR Response Based on DAS28 by Visit(Weeks 3, 5, 9, 13, 17, 21 and 25)
- Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit(Baseline, Week 3, 5, 9, 13, 17, 21 and 25)