NCT00988221已完成3 期
A 24 Week Randomized, Double-blind, Placebo-controlled Withdrawal Trial With a 16 Week Open-label lead-in Phase, and 64 Week Open-label Follow-up, to Evaluate the Effect on Clinical Response and the Safety of Tocilizumab in Patients With Active Polyarticular-course Juvenile Idiopathic Arthritis
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 188
- 试验地点
- 69
- 主要终点
- Percent of Patients With a Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30 (ACR30) Flare in Part II of the Study (Weeks 16-40)
研究概览
简要总结
This 3-part study evaluated the efficacy and safety of tocilizumab in patients with active polyarticular-course juvenile idiopathic arthritis who have an inadequate response to, or were intolerant of methotrexate. In Part I of the study, all patients received intravenous (iv) infusions of tocilizumab (8 mg/kg for patients ≥ 30kg, 8 mg/kg or 10 mg/kg for patients < 30kg) every 4 weeks for 16 weeks. In Part II of the study, patients with an adequate response in Part I were randomized to receive either tocilizumab at the same dose as in Part I or placebo every 4 weeks for up to 24 weeks. In Part III of the study, patients received tocilizumab at the same dose as in Part I every 4 weeks for up to another 64 weeks. Standard of care therapy with or without non-steroidal anti-inflammatory drugs (NSAID), corticosteroids, or methotrexate was continued throughout the study.
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
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children/juveniles, 2-17 years of age.
- •Polyarticular-course juvenile idiopathic arthritis (pcJIA) ≥ 6 months duration.
- •Active disease (≥ 5 active joints, ≥ 3 with limitation of motion).
- •Inadequate response to or inability to tolerate methotrexate.
- •Methotrexate, oral corticosteroids, and non-steroidal anti-inflammatory drugs (NSAID) at stable dose(at least 8, 4, and 2 weeks,respectively) prior to baseline.
- •Biologics discontinued, between at least 1 and 20 weeks prior to baseline, depending on biologic.
排除标准
- •Auto-immune, rheumatic disease or overlap syndrome other than pcJIA.
- •Wheelchair bound or bedridden.
- •Intra-articular, intramuscular, intravenous, or long-acting corticosteroids within 4 weeks prior to baseline.
- •Disease-modifying anti-rheumatic drugs (DMARD) (other than methotrexate) within 4 weeks prior to baseline.
- •Previous treatment with tocilizumab.
研究组 & 干预措施
Tocilizumab 10 mg/kg in patients weighing < 30 kg
Experimental
Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.
干预措施: Tocilizumab (Drug)
Tocilizumab 8 mg/kg in patients weighing < 30 kg
Experimental
Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.
干预措施: Tocilizumab (Drug)
Tocilizumab 8 mg/kg in patients weighing ≥ 30 kg
Experimental
Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.
干预措施: Tocilizumab (Drug)
Placebo
Placebo Comparator
Patients received placebo to tocilizumab intravenously every 4 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Percent of Patients With a Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30 (ACR30) Flare in Part II of the Study (Weeks 16-40)
时间窗: Week 16 through Week 40
JIA ACR30 flare is defined as a ≥ 30% worsening of 3 of 6 variables and no more than 1 of the remaining variables improving \> 30%. The 6 variables are physician global assessment of disease activity (worsening of 20 units minimum on a 0-100 visual analog scale \[VAS\]), parent/patient global assessment of overall well-being (worsening of 20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0\[best\]-3\[worst\]). Patients who withdrew or who took escape medication are classified as flared. The analysis used the Cochran-Mantel-Haenszel test with the stratification variables background use of methotrexate and oral corticosteroids applied at Week 16.
次要结局
- Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Limitation of Movement at the End of Part I of the Study (Week 16)(Baseline to Week 16)
- Percent of Patients With Inactive Disease at the End of Part I of the Study (Week 16)(Week 16)
- Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Active Arthritis at the End of Part I of the Study (Week 16)(Baseline to Week 16)
- Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Erythrocyte Sedimentation Rate (ESR) at the End of Part I of the Study (Week 16)(Baseline to Week 16)
- Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Functional Ability at the End of Part I of the Study (Week 16)(Baseline to Week 16)
- Juvenile Arthritis Disease Activity Score (JADAS-27) at the End of Part I of the Study (Week 16)(Week 16)
- Pain Visual Analogue Scale (VAS) Score at the End of Part I of the Study (Week 16)(Week 16)
- Percent of Patients With an Elevated C-reactive Protein Concentration at Baseline That Had Normalized at the End of Part I of the Study (Week 16)(Baseline to Week 16)
- Percent of Patients With an Elevated Platelet Count at Baseline That Had Normalized at the End of Part I of the Study (Week 16)(Baseline to Week 16)
- Percent of Patients With an Elevated White Blood Count at Baseline That Had Normalized at the End of Part I of the Study (Week 16)(Baseline to Week 16)
- Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses in Part I of the Study (Baseline to Week 16)(Baseline to Week 16)
- Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Patient/Parent Global Assessment of Overall Well-being at the End of Part I of the Study (Week 16)(Baseline to Week 16)
- Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Physician Global Assessment of Disease Activity at the End of Part I of the Study (Week 16)(Baseline to Week 16)
- Percent of Patients With an Elevated Erythrocyte Sedimentation Rate at Baseline That Had Normalized at the End of Part I of the Study (Week 16)(Baseline to Week 16)
- Percent of Patients With Inactive Disease at the End of Part II of the Study (Week 40)(Week 40)
- Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at Weeks 2, 52, and 104(Week 2 to Week 104)
- Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at the End of Part II of the Study (Week 40)(Week 40)
- Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Physician Global Assessment of Disease Activity at the End of Part II of the Study (Week 40)(Baseline to Week 40)
- Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Patient/Parent Global Assessment of Overall Well-being at the End of Part II of the Study (Week 40)(Baseline to Week 40)
- Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Active Arthritis at the End of Part II of the Study (Week 40)(Baseline to Week 40)
- Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Limitation of Movement at the End of Part II of the Study (Week 40)(Baseline to Week 40)
- Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Erythrocyte Sedimentation Rate (ESR) at the End of Part II of the Study (Week 40)(Baseline to Week 40)
- Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) at the End of Part II of the Study (Week 40)(Baseline to Week 40)
- Change From Baseline in the Pain Visual Analogue Scale (VAS) Score at the End of Part II of the Study (Week 40)(Baseline to Week 40)
- Percent of Patients With 4 Baseline Disease Characteristics Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at Week 104(Week 104)
- Change From Baseline in the Juvenile Arthritis Disease Activity Score-71 (JADAS-71) at Week 104(Baseline to Week 104)
- Percent of Patients With a Minimally Important Improvement in the Children's Health Assessment Questionnaire-Disability Index (CHAQ-DI) Score at Weeks 16, 40, 52, 80, and 104(Baseline to Week 104)
- Change From Baseline in the Pain Visual Analogue Scale (VAS) Score at Weeks 2, 40, 52, and 104(Baseline to Week 104)
- Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Physician Global Assessment of Disease Activity at Week 104(Baseline to Week 104)
- Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Limitation of Movement at Week 104(Baseline to Week 104)
- Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Functional Ability at Week 104(Baseline to Week 104)
- Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Patient/Parent Global Assessment of Overall Well-being at Week 104(Baseline to Week 104)
- Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Active Arthritis at Week 104(Baseline to Week 104)
- Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Erythrocyte Sedimentation Rate (ESR) at Week 104(Baseline to Week 104)
- C-reactive Protein Levels From Baseline to Week 104(Baseline to Week 104)
- Percent of Patients With Inactive Disease From Week 16 to Week 104(Week 16 to Week 104)
- Percent of Patients in Clinical Remission From Week 40 to 104(Week 40 to Week 104)
- Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at Week 104 by Duration of Disease (< 2 Years, ≥ 2 Years)(Baseline to Week 104)
- Oral Corticosteroid Dose at Baseline, Week 52, and Week 104(Baseline to Week 104)
- Methotrexate Dose at Baseline, Week 52, and Week 104(Baseline to Week 104)
- Height Standard Deviation Score at Baseline, Week 52, and Week 104(Baseline to Week 104)
研究者
研究点 (69)
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