Long-term Extension Study of Safety During Treatment With Tocilizumab (MRA) in Patients Completing Treatment in WA17822
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 538
- 主要终点
- Adverse Event (AE) Summary Over Time
研究概览
简要总结
This open-label, international multi-center extension study WA18695 was designed to assess the long term safety of tocilizumab in patients who had moderate to severe active rheumatoid arthritis (RA). Patients enrolled in the WA18695 study had previously received treatment in the 24-week, placebo-controlled, Phase III Study WA17822. Eligible patients were assigned to treatment with 8 mg/kg tocilizumab every 4 weeks for a maximum of 5 years.
详细描述
The primary objective of this extension study was to assess the long-term safety of 8 mg/kg tocilizumab with regard to adverse events (AEs) and laboratory result abnormalities.
The secondary objectives were as follows:
- To explore the possibility of reducing concomitant steroid treatment
- To determine the long-term efficacy of 8 mg/kg tocilizumab with regard to reduction in signs and symptoms
- To better understand and predict tocilizumab efficacy, response, safety, and progression of rheumatoid arthritis (RA) and associated diseases with regard to its effect on biomarkers
No viable biomarkers for TCZ treatment effects were identified from the controlled studies. There were, therefore, no biomarkers that warranted further investigation in long-term studies, so no biomarker data are reported.
The extension study WA18695 was an open-label, international multi-center study in patients with moderate to severe active rheumatoid arthritis (RA) who had completed treatment in the 24 weeks placebo-controlled Phase III study WA17822. Patients entering WA17822 had an inadequate response to methotrexate (MTX), and, during WA17822, patients had received treatment with intravenous infusions of tocilizumab 4 mg/kg, 8 mg/kg, or placebo every 4 weeks with background MTX therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who have completed participation in the Phase III study WA17822 (NCT00106548) in adult rheumatoid arthritis.
排除标准
- •Treatment with any investigational agent since the last administration of study drug in WA
- •Treatment with intravenous (IV) gammaglobulin, plasmapheresis, or Prosorba column since the last administration of study drug in WA
- •Treatment with an anti-tumor necrosis factor or anti-interleukin-1 agent, or a T cell costimulation modulator since the last administration of study drug in WA
- •Previous treatment with any cell-depleting therapies.
- •Parenteral, intramuscular, or intra-articular corticosteroids within 6 weeks prior to baseline.
研究组 & 干预措施
Tocilizumab 8 mg/kg
All participants received tocilizumab 8 mg/kg to a maximum of 800 mg, administered by intravenous (IV) infusion over one hour, every 4 weeks. Concomitant therapies were limited to dosage and administration constraints detailed in the protocol.
干预措施: Tocilizumab (Drug)
结局指标
主要结局
Adverse Event (AE) Summary Over Time
时间窗: through 264 Weeks
The number of participants experiencing at least one adverse event (AE) is recorded for each 12-month time period, with multiple occurrences in a single individual counted. Because months were calculated as 28 days, the periods actually equate to 48 weeks.
Summary Adverse Event Rates Over Time
时间窗: through 264 Weeks
Patient year (PY) refers to duration in study, calculated from first active drug intake to last safety assessment available + 1. Patient year rates with confidence interval were calculated for adverse events of interest in evaluating the long-term safety of the product being studied. Abbreviations include the following: adverse event (AE), adverse event of special interest (AESI), gastrointestinal (GI), serious adverse event (SAE), and investigational product (IP). Hypersensitivity events were defined as AEs that occurred during or within 24 hours of IP infusion and were not deemed "unrelated" to trial treatment by the investigator. This definition includes all types of AEs, regardless of whether or not they were consistent with hypersensitivity. Medical confirmation of the AESI "GI perforation" was based on medical adjudication of events captured by the GI Perforation Standardised MedDRA Queries (SMQs).
Overall Death Rate Over Time
时间窗: through 264 Weeks
Patient year (PY) refers to duration in study, calculated from first active drug intake to last safety assessment available + 1. To calculate the death rate, the total cumulative number of years that all participants were exposed to the drug, from first active drug intake to last safety assessment available + 1, was calculated as 2461.94. Since 10 participants died during that time, the death rate per year was not informative (0.00). Therefore, the overall death rate was calculated with the confidence interval based on events per 100 patient years exposure.
次要结局
- Participants Showing Improvement in Rheumatoid Arthritis Symptoms Over Time, Through 264 Weeks(through 264 Weeks)
- Percentage of Participants Classified as Responders by EULAR Response Over Time, Through 264 Weeks(through 264 Weeks)
- Percentage of Participants Classified as Responders by Disease Activity Scores Over Time, Through 264 Weeks(through 264 Weeks)
- Percentage of Participants With at Least a 5-point Improvement From Baseline in Quality of Life Measure for Fatigue Over Time, Through 264 Weeks(through 264 Weeks)
- Change From Baseline in Scores for Swollen and Tender Joint Counts Over Time, Through 264 Weeks(through 264 Weeks)
- Change From Baseline in Scores for Health Assessment Questionnaire - Disability Index Over Time, Through 264 Weeks(through 264 Weeks)
- Change From Baseline in Scores for Patient's Global Assessment of Disease Activity Over Time, Through 264 Weeks(through 264 Weeks)
- Change From Baseline in Scores for Physician's Global Assessment of Disease Activity Over Time, Through 264 Weeks(through 264 Weeks)
- Change From Baseline in Scores for Patient's Level of Pain Over Time, Through 264 Weeks(through 264 Weeks)
- Percentage of Participants With at Least a 5-point Improvement From Baseline in Quality of Life Using the 36-Item Short-Form Health Survey (SF-36) Over Time, Through 264 Weeks(through 264 Weeks)