Comparative Pharmacokinetic, Pharmacodynamic, Safety and Efficacy Study of Three Anti-CD20 Monoclonal Antibodies in Patients With Moderate to Severe Rheumatoid Arthritis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 276
- 试验地点
- 56
- 主要终点
- AUC0-∞ Over the Entire Course of Therapy (2 Doses) From Day 1 Through Week 16.
研究概览
简要总结
This study will compare the plasma pharmacokinetic profile and the change in disease activity score in patients with active rheumatoid arthritis following treatment with two 1000 mg doses of DRL_RI or one of two sources of rituximab (Rituxan® or MabThera®). Patients will also be monitored for safety, B cell depletion and recovery, and for the development of immune responses to the administered study drugs
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients, 18 to 65 years of age
- •Diagnosis of RA, according to ACR criteria (1987), of at least 6 months duration
- •At randomization, tender joint count ≥ 6 and swollen joint count ≥ 6
- •Evidence of at least moderate disease activity
- •Patients receiving oral or parenteral MTX with a dose of 15 to 25 mg per week when given alone or 10 to 25 mg per week in combination with additional non-biologic DMARD(s) for at least 6 months and on stable dose for at least 3 months
- •Patients must be on a stable dose of folic acid or equivalent (≥5 mg per week)
- •Chest X-ray not suggestive of any lung infections including pulmonary tuberculosis (TB)
- •Contraception required per protocol
排除标准
- •Prior therapy with
- •Rituximab, abatacept, tocilizumab, anakinra or an agent/antibody targeting CD20, CD19 or B cells
- •Tumor necrosis factor (TNF) alfa antagonists or other biologic DMARDs
- •Other prior or concurrent therapies may also be excluded
- •Any clinically relevant abnormality detected on screening history, physical examination, clinical laboratory, chest X-ray, or electrocardiogram (ECG), other than values consistent with RA
- •Evidence of active, suspected or inadequately treated TB
- •Positive serological test for hepatitis C virus antibodies, hepatitis B surface antigen, hepatitis B core antibody, or human immunodeficiency virus
- •History of cardiovascular disease, history of stroke, or uncontrolled hypertension
- •History of lymphoproliferative disease or organ allograft
- •History of cancer (except for in situ cancer, excised, or limited stage, curatively treated cancer with no sign of disease for >5 years)
- •History of allergy (medication history) to any of the compounds used in the study
- •Pregnant or lactating women or women planning to become pregnant during the study
结局指标
主要结局
AUC0-∞ Over the Entire Course of Therapy (2 Doses) From Day 1 Through Week 16.
时间窗: 16 weeks
PK samples were collected pre-infusion; 3 hours post infusion; EOI; and at 1, 6, 24, 48, 168 hours post End of Infusion. A PK sample at 336 hours post EOI were also to be collected after the second dose.
Area Under the Concentration-Time Curve From Time 0 to 336 Hours (AUC0-336) Post First Dose
时间窗: 2 weeks
PK samples were collected pre-infusion; 3 hours post infusion; EOI; and at 1, 6, 24, 48, 168 hours post End of Infusion. A PK sample at 336 hours post EOI were also to be collected after the second dose.
Area Under Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-t) (Second Dose).
时间窗: 16 weeks
PK samples were collected pre-infusion; 3 hours post infusion; EOI; and at 1, 6, 24, 48, 168 hours post End of Infusion. A PK sample at 336 hours post EOI were also to be collected after the second dose
次要结局
- Time to Cmax (Tmax) After First Dose.(2 weeks)
- Terminal Half-life (t1/2)(24 weeks)
- Mean Change in Disease Activity Score-C Reactive Protein (DAS28-CRP) From Baseline Per Unit Time at Weeks 4(Baseline and 4 weeks)
- Maximum Plasma Concentration (Cmax) After First Dose(2 weeks)
- Mean Change in DAS28-CRP From Baseline Per Unit Time at Week 12.(Baseline and 12 weeks)
- Time to Cmax (Tmax) After Second Dose(2 weeks)
- Volume of Distribution (Vz)(24 weeks)
- Percentage of Patients With Peripheral B-cell Counts Depletion at Week 24.(24 weeks)
- Percentage of Patients With ACR50 at Week 24(24 weeks)
- Percentage of Patients With ACR70 Response at Week 24(24 weeks)
- Maximum Plasma Concentration (Cmax) After Second Dose(2 weeks)
- Systemic Clearance (CL)(24 weeks)
- Mean Change in DAS28-CRP From Baseline Per Unit Time at 8 Weeks.(Baseline and 8 weeks)
- Mean Change in Disease Activity Score- C Reactive Protein (DAS28-CRP) From Baseline Per Unit Time at Week 16.(Baseline and 16 weeks)
- Percentage of Patients With ACR20 at Week 24(24 weeks)
- Percentage of Patients With B-cell Counts 20% Below the Lower Limit of Normal(48 hours)
- Percentage of Patients With Peripheral B-cell Counts Depletion at Week 16.(16 weeks)
- Change From Baseline in HAQ-DI at Week 24.(24 weeks)