A Mechanism of Action Study to Evaluate the Effects of IL-6 Receptor Blockade With Tocilizumab (TCZ) on Lipids, Arterial Stiffness, and Markers of Atherogenic Risk in Patients With Moderate to Severe Active Rheumatoid Arthritis (RA).
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 132
- 试验地点
- 40
- 主要终点
- Change From Baseline in Small Low Density Lipoprotein (sLDL) Particle Numbers
研究概览
简要总结
This 2 arm study will investigate the effects of tocilizumab on lipids, arterial stiffness, and markers of atherogenic risk in patients with moderate to severe active rheumatoid arthritis. In Part 1 of the study, patients will be randomized to receive either tocilizumab 8mg/kg intravenously or placebo every 4 weeks, in combination with methotrexate 7.5-25 mg weekly. In Part 2, all patients will receive open-label treatment with tocilizumab plus methotrexate.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •adult patients, 18-75 years of age
- •rheumatoid arthritis (RA) of >6 months duration
- •able to receive outpatient treatment
- •on methotrexate for at least 12 weeks before entering study, at a stable dose of 7.5-25 mg/week for the last 8 weeks
- •oral corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDS) permitted, if at a stable dose for 4 weeks before study start
- •Exclusion Criteria
- •major surgery (including joint surgery) within 8 weeks prior to screening, or planned surgery within 6 months after entering study
- •history of, or current inflammatory joint disease or rheumatic autoimmune disease other than RA
- •inadequate response to anti-tumor necrosis factor (TNF) agent during the 6 months prior to baseline, or inadequate response to >2 anti-TNF agents
- •initiation of treatment with lipid lowering agents within 12 weeks prior to baseline
排除标准
- 未提供
研究组 & 干预措施
TCZ + MTX
Participants received 8 mg/kg tocilizumab (TCZ) by intravenous infusion (IV) every 4 weeks plus methotrexate (MTX) 7.5-25 mg (oral or parenteral) weekly for the first 24 weeks. From Week 24 to Week 104, participants received open-label TCZ 8 mg/kg every 4 weeks plus 7.5-25 mg MTX weekly.
干预措施: Methotrexate (Drug)
TCZ + MTX
Participants received 8 mg/kg tocilizumab (TCZ) by intravenous infusion (IV) every 4 weeks plus methotrexate (MTX) 7.5-25 mg (oral or parenteral) weekly for the first 24 weeks. From Week 24 to Week 104, participants received open-label TCZ 8 mg/kg every 4 weeks plus 7.5-25 mg MTX weekly.
干预措施: Tocilizumab (Drug)
Placebo + MTX
Participants received placebo intravenous infusion (IV) every 4 weeks plus methotrexate (MTX) 7.5-25 mg (oral or parenteral) weekly for the first 24 weeks. From Week 24 to 104, participants received open-label tocilizumab (TCZ) 8 mg/kg every 4 weeks plus 7.5-25 mg MTX.
干预措施: Tocilizumab (Drug)
Placebo + MTX
Participants received placebo intravenous infusion (IV) every 4 weeks plus methotrexate (MTX) 7.5-25 mg (oral or parenteral) weekly for the first 24 weeks. From Week 24 to 104, participants received open-label tocilizumab (TCZ) 8 mg/kg every 4 weeks plus 7.5-25 mg MTX.
干预措施: Placebo (Drug)
Placebo + MTX
Participants received placebo intravenous infusion (IV) every 4 weeks plus methotrexate (MTX) 7.5-25 mg (oral or parenteral) weekly for the first 24 weeks. From Week 24 to 104, participants received open-label tocilizumab (TCZ) 8 mg/kg every 4 weeks plus 7.5-25 mg MTX.
干预措施: Methotrexate (Drug)
结局指标
主要结局
Change From Baseline in Small Low Density Lipoprotein (sLDL) Particle Numbers
时间窗: Baseline and Week 12
Small LDL particles are associated with an increased risk of cardiovascular disease: more of these small particles lead to a greater risk. The concentration of fasting small LDL particles was determined using the Nuclear Magnetic Resonance (NMR) methodology.
Change From Baseline to Week 12 in Aortic Pulse Wave Velocity (PWV)
时间窗: Baseline and Week 12
Aortic (central) arterial stiffness was assessed with Pulse Wave Analysis (PWA) of the radial artery and carotid-femoral PWV using applanation tonometry after the patient had rested in a supine position for at least 10 minutes.
次要结局
- Number of Participants Experiencing Adverse Events (AEs)(Up to Week 24)
- Change From Baseline to Week 24 in Small Low Density Lipoprotein (sLDL) Particle Numbers(Baseline and Week 24)
- Change From Baseline to Week 24 in Aortic Pulse Wave Velocity (PWV)(Baseline and Week 24)