A Double-Blind, Randomized, Parallel-Group Study to Investigate the Pharmacokinetic and Clinical Similarity Between MabionCD20, EU-approved MabThera® and US-licensed Rituxan® in Patients With Moderate-to-Severe Rheumatoid Arthritis
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 发起方
- Mabion SA
- 主要终点
- Area Under the Serum Concentration-time Curve from Day 1 to Week 24, with extrapolation to infinity [AUC 0-inf (D1-W24)]
研究概览
简要总结
Primary objective of the study is to establish a 3-way PK similarity bridge between MabionCD20 (candidate biosimilar to rituximab), MabThera® (EU-sourced rituximab) and Rituxan® (US-sourced rituximab) following the administration of these drugs to patients with moderate-to-severe rheumatoid arthritis. Main secondary objective is to confirm therapeutic similarity between MabionCD20 and the reference rituximab.
详细描述
Patients with active moderate-to-severe rheumatoid arthritis diagnosed according to the 2010 ACR criteria will be randomized to receive a blinded treatment course of either MabionCD20, EU-Rituximab (MabThera®) or US-Rituximab (Rituxan®) on the top of a stable methotrexate therapy. Two infusions of investigational drug at a dose of 1000 mg will be given at Day 1 and 15. Patients will be then followed for a minimum of 24 weeks to establish PK and therapeutic similarity and to compare PD, safety and immunogenicity parameters between the three rituximab products (Main Phase). Patients may receive a second course of investigational therapy at Week 24, provided that they meet re-treatment eligibility criteria specified in the study protocol. Subjects in MabionCD20 and EU-Rituximab groups will be continued on their assigned treatments, while all subjects in US-Rituximab group will be switched to MabionCD20. All subjects (re-treated and not re-treated) will continue the follow-up until Week 48 to collect long-term safety, immunogenicity and efficacy data.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Area Under the Serum Concentration-time Curve from Day 1 to Week 24, with extrapolation to infinity [AUC 0-inf (D1-W24)]
时间窗: Day 1 to Week 24
Concentration of rituximab in serum over the entire PK study duration, with extrapolation to infinity. Outcome based on all PK samples collected in the study - from Day 1 (first infusion) to Week 24 (before administration of the 2nd treatment course).
Area Under the Serum Concentration-time Curve from Day 1 to Day 15 [AUC 0-t (D1-D15)]
时间窗: Day 1 to Day 15
Concentration of rituximab in serum measured from Day 1 (before the 1st drug infusion) to Day 15 (before the 2nd drug infusion).
次要结局
- Maximum drug concentration in serum after the 1st infusion (Cmax1)(Day 1)
- Percentage of patients with low disease activity (DAS28-ESR <3.2)(Baseline to Week 48)
- Percentage of patients with a good response on EULAR scale(Baseline to Week 48)
- Percentage of patients with a moderate response on EULAR scale(Baseline to Week 48)
- Simplified Disease Activity Index (SDAI)(Baseline to Week 48)
- Clinical Disease Activity Index (CDAI)(Baseline to Week 48)
- Area Under the Serum Concentration-time Curve from Day 1 to Week 24 [AUC 0-t (D1-W24)](Baseline to Week 24)
- Area Under the Serum Concentration-time Curve from Day 15 to Week 24 [AUC 0-t (D15-W24)](Day 15 to Week 24)
- Maximum drug concentration in serum after the 2nd infusion (Cmax2)(Day 15)
- Time to achieve maximum drug concentration in serum after the 2nd infusion (Tmax2)(Day 15)
- Trough drug concentration in serum (Ctrough)(Day 15)
- Time to achieve maximum drug concentration in serum after the 1st infusion (Tmax1)(Day 1)
- Mean Change from Baseline in DAS28-ESR score(Baseline to Week 48)
- Mean Change from Baseline in DAS28-CRP score(Baseline to Week 48)
- Percentage of patients with disease remission (DAS28-ESR <2.6)(Baseline to Week 48)
- Percentage of patients achieving an ACR20/50/70 response(Baseline to Week 48)
- Absolute CD19+ B cell counts by visit(Day 1 to Week 24)
- Percentage of patients with undetectable levels of CD19+ B-cells(Day 3 and Week 24)
- Percentage of patients with Adverse Events (AEs)(Day 1 to Week 48)
- Percentage of patients with a positive anti-drug antibody (ADA) response(Day 1 to Week 48)