An Open-label, Exploratory Study of the Pharmacokinetic and Pharmacodynamic Activity of MabThera in Combination With Methotrexate in Synovial Tissue and in Peripheral Blood of Patients With Active Rheumatoid Arthritis.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 3
- 主要终点
- Change From Baseline in Absolute B Cell Cluster Differential 19 Positive (CD19+) Counts in Synovial Tissues
研究概览
简要总结
This single arm study will investigate the pattern of B cell depletion in synovial tissue and peripheral blood of patients with active RA, after MabThera (1000mg iv x 2 on days 1 and 15) + methotrexate (10-25mg/week po) treatment. The clinical efficacy and pharmacokinetic profile of MabThera after treatment and retreatment will also be investigated. The anticipated time on study treatment is 2+ years, and the target sample size is <100 individuals.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •adult patients 18-80 years of age;
- •RA for >=3 months;
- •receiving outpatient treatment;
- •failed treatment with >=1 DMARD (but not anti TNF or other biologic therapy);
- •inadequate response to methotrexate, having taken and tolerated it for >=12 weeks, with a stable dose for >=4 weeks.
排除标准
- •rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA;
- •history of, or current, inflammatory joint disease other than RA, or other systemic autoimmune disorder;
- •diagnosis of RA before the age of 16;
- •bone/joint surgery within 12 weeks of study;
- •prior use of anti-TNF or other biologic therapy, an anti-alpha 4 integrin, or any cell-depleting therapies.
研究组 & 干预措施
1
干预措施: rituximab [MabThera/Rituxan] (Drug)
1
干预措施: Methotrexate (Drug)
结局指标
主要结局
Change From Baseline in Absolute B Cell Cluster Differential 19 Positive (CD19+) Counts in Synovial Tissues
时间窗: Weeks 12, 24, and 36
The change from baseline in absolute B cell (CD19+) counts at each visit calculated as (B cell count at visit minus B cell count at baseline) for synovial tissues.
Change From Baseline in Absolute B Cell CD19+ Counts in Peripheral Blood
时间窗: Weeks 4, 12, 24, 36, and 48
The change from baseline in absolute B cell (CD19+) count at each visit calculated as (B cell count at visit minus B cell count at baseline) for peripheral blood.
次要结局
- Change From Baseline in Levels of Key Cytokines (Interleukin [IL]-1beta [β], Tumor Necrosis Factor [TNF]-Alpha [α], IL-4, IL-6, IL-10, and IL-13) in Blood (Serum)(Days 15 and 183 and Weeks 4, 12, 24, 36, and 48)
- Change From Baseline in Modified Total Sharp Score (mTSS)(Weeks 24 and 48)
- Change From Baseline in Absolute Counts of Cells Expressing CD20+ and CD22+ in Absolute B Cell (CD19+) Counts in Synovial Tissues(Weeks 12, 24, and 36)
- Change From Baseline in Absolute Counts of Cells Expressing CD20+ and CD22+ in Absolute B Cell (CD19+) Counts in Peripheral Blood(Weeks 4,12, 24, 36, and 48)
- Change From Baseline in Levels of Key Cytokines in (IL-1β, TNF-α, IL-6, and IL-10) in Synovial Tissues(Weeks 12, 24, and 36)
- Change From Baseline in Myelocytomatosis Oncogene (C-myc) and BCL2-associated X Protein (BAX) in Peripheral Blood(Days 15 and 183)
- Percentage of Participants Achieving American College of Rheumatology 20 Percent (20%) 50%, and 70% (ACR20/50/70) Response(Week 48)
- Change From Baseline in Disease Activity Score Based on 28 Joint Count (DAS28) Erythrocyte Sedimentation Rate (ESR) Score(Weeks 12, 24, 36, and 48)
- Percentage of Participants Achieving Response by European League Against Rheumatism (EULAR) Category(Weeks 24, 36, and 48)
- Change From Baseline in Erosion Score(Weeks 24 and 48)
- Change From Baseline in Joint Space Narrowing (JSN) Score(Weeks 24 and 48)
- Change From Baseline in ACR Core Set(Week 48)