Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of Tocilizumab in Patients With Active Rheumatoid Arthritis on Background Non-biologic DMARDs and Monotherapy Who Have an Inadequate Response to Current Non-Biologic or Biologic DMARDs
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 886
- 主要终点
- Percentage of Participants Experiencing at Least One Serious Adverse Event (SAE) During the 24 Week Treatment Period
研究概览
简要总结
This 3 arm randomized open label study will evaluate the safety, tolerability and efficacy of tocilizumab in patients with moderate to severe active rheumatoid arthritis, who have had inadequate response to or are unable to tolerate DMARDs. The protocol incorporates risk mitigation strategies developed in partnership with the FDA to manage known and potential risks associated with the treatment of tocilizumab. Patients will be randomized to receive tocilizumab either 4 mg/kg intravenous (iv) or 8 mg/kg iv with concomitant non-biologic DMARDs, or 8 mg/kg iv without concomitant non-biologic DMARDs, every 4 weeks, for a total of 6 infusions. The anticipated time on study treatment is 3-12 months, and the target sample size is 500-1000 individuals.
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
- 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
- •adult patients, >=18 years of age;
- •moderate to severe active rheumatoid arthritis for >6 months;
- •inadequate clinical response or unable to tolerate current or prior biologic or non-biologic Disease-modifying antirheumatic drug (DMARD) therapy;
- •Swollen joint count (SJC) >/=4 and Tender joint count (TJC) >/=4
- •body weight </=150kg
- •current permitted non-biologic DMARDs must be on stable dose for >/= 7 weeks prior to baseline;
排除标准
- •history of autoimmune disease or inflammatory joint disease other than rheumatoid arthritis;
- •functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in rheumatoid arthritis;
- •treatment with rituximab within 6 months before screening;
- •intraarticular corticosteroids within 8 weeks or intramuscular (im)/ intravenous (iv) corticosteroids within 12 weeks prior to screening;
- •known active current or history of recurrent infections, or any major episode of infection requiring hospitalization or treatment with iv antibiotics within 4 weeks of screening, or oral antibiotics within 2 weeks prior to screening.
研究组 & 干预措施
Tocilizumab 8 mg/kg Monotherapy
Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase at the investigator's discretion.
干预措施: tocilizumab [RoActemra/Actemra] (Drug)
Tocilizumab 4 mg/kg + DMARD
Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase at the investigator's discretion.
干预措施: tocilizumab [RoActemra/Actemra] (Drug)
Tocilizumab 4 mg/kg + DMARD
Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase at the investigator's discretion.
干预措施: Nonbiologic DMARDs of investigator's choice (Drug)
Tocilizumab 8 mg/kg + DMARD
Participants received Tocilizumab (TCZ) 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase at the investigator's discretion.
干预措施: tocilizumab [RoActemra/Actemra] (Drug)
Tocilizumab 8 mg/kg + DMARD
Participants received Tocilizumab (TCZ) 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase at the investigator's discretion.
干预措施: Nonbiologic DMARDs of investigator's choice (Drug)
结局指标
主要结局
Percentage of Participants Experiencing at Least One Serious Adverse Event (SAE) During the 24 Week Treatment Period
时间窗: 24 Weeks
An SAE was any adverse event that at any dose fulfilled at least one of the following criteria: * Was fatal (results in death) * Was life-threatening * Required in-patient hospitalization or prolongation of existing hospitalization * Resulted in persistent or significant disability/incapacity * Was a congenital anomaly/birth defect * Was medically significant or required intervention to prevent one or other of the outcomes listed above.
次要结局
- Percentage of Participants Experiencing Serious Adverse Events of Special Interest(24 Weeks)
- Percentage of Participants Experiencing Non-serious Adverse Events of Special Interest(24 Weeks)
- Percentage of Participants Achieving Clinical Remission at Weeks 8, 16, and 24(Weeks 8,16,24)
- Change From Baseline in DAS28 Score at Weeks 8, 16 and 24(Baseline, Weeks 8,16,24)
- Percentage of Participants Achieving American College of Rheumatology (ACR) (ACR20/50/70) Responses at Weeks 8, 16, and 24(Baseline, Weeks 8,16,24)
- Percentage of Participants With Tocilizumab Dose Increased From 4 mg/kg to 8 mg/kg at Week 8(Baseline, Week 8)
- Number of Participants Having Their Tocilizumab Dose Increased From 4 mg/kg to 8 mg/kg at Weeks 12, 16, and 20(Weeks 12,16, 20)
- Change From Baseline in Routine Assessment Patient Index Data (RAPID3) Score at Weeks 8, 16, and 24(Baseline, Weeks 8,16,24)
- Change From Baseline in Fatigue Visual Analogue Scale (VAS) at Weeks 8, 16, and 24(Baseline, Weeks 8,16,24)