A Randomized, Placebo-controlled Study to Evaluate the Effect of Tocilizumab on Disease Response in Patients With Active Systemic Juvenile Idiopathic Arthritis (JIA), With an Open-label Extension to Examine the Long Term Use of Tocilizumab
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 112
- 主要终点
- Part I: Percentage of Participants With ≥30% Improvement in Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Core Set and Absence of Fever
研究概览
简要总结
This study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in patients with active systemic juvenile idiopathic arthritis (sJIA) who have an inadequate clinical response to NSAIDs and corticosteroids. In Part I of the study patients will be randomized 2:1 to receive iv infusions of RoActemra/Actemra (8mg/kg iv for patients >=30kg, or 12mg/kg for patients <30kg) or placebo, every 2 weeks. Stable NSAIDs and methotrexate will be continued throughout. After 12 weeks of double-blind treatment, all patients will have the option to enter Part II of the study to receive open-label treatment with RoActemra/Actemra for a further 92 weeks, followed by a 3-year continuation of the study in Part III in which, for patients who meet specific criteria, an optional alternative dosing schedule decreasing the study drug administration frequency will be introduced. Anticipated time on study treatment is up to 5 years.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Patients aged 2-17 years of age
- •Systemic juvenile idiopathic arthritis with >= 6 months persistent activity
- •Presence of active disease (>=5 active joints, or >=2 active joints + fever + steroids)
- •Inadequate clinical response to nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids due to toxicity or lack of efficacy
排除标准
- •Wheelchair-bound or bed-ridden
- •Any other autoimmune, rheumatic disease or overlap syndrome other than systemic juvenile idiopathic arthritis
- •Intravenous long-acting corticosteroids or intra-articular corticosteroids within 4 weeks of baseline, or throughout study
- •Disease-modifying antirheumatic drugs (DMARDs), other than methotrexate
- •Previous treatment with tocilizumab
研究组 & 干预措施
2
干预措施: corticosteroids (Drug)
1
干预措施: tocilizumab [RoActemra/Actemra] (Drug)
1
干预措施: Non-steroidal anti-inflammatory drugs (NSAIDs) (Drug)
1
干预措施: methotrexate (Drug)
1
干预措施: corticosteroids (Drug)
2
干预措施: Placebo (Drug)
2
干预措施: Non-steroidal anti-inflammatory drugs (NSAIDs) (Drug)
2
干预措施: methotrexate (Drug)
结局指标
主要结局
Part I: Percentage of Participants With ≥30% Improvement in Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Core Set and Absence of Fever
时间窗: Baseline, Week 12
Percentage of participants with ≥30% improvement in ACR core set consisting of 6 components: 1) Physician's global assessment of disease activity Visual Analog Scale (VAS), 2) Parent/Patient global assessment of overall well-being VAS, 3) Maximum number of joints with active arthritis, 4) Number of joints with limitation of movement, 5) Erythrocyte Sedimentation Rate, and 6) Childhood Health Assessment Questionnaire- Disability Index (CHAQ-DI) consisting of 30 questions in 8 domains. Absence of fever was defined as no diary temperature recording ≥37.5° Celsius in the preceding seven days.
Part II: Percentage of Participants With Decreases in Oral Corticosteroid Dose at Week 104
时间窗: Baseline, Week 104
Percentage of participants with ≥20 percent, ≥50 percent, ≥75 percent and ≥90 percent decreases in oral corticosteroid dose (mg/kg/day) from baseline.
次要结局
- Part I: Percentage of Participants With JIA Core Set ACR 30/50/70/90 Response at Week 12(Baseline, Week 12)
- Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Parent/Patient Global Assessment of Overall Well-being(Baseline, Week 12)
- Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Physician's Global Assessment of Disease Activity(Baseline, Week 12)
- Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Maximum Number of Joints With Active Arthritis(Baseline, Week 12)
- Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Number of Joints With Limitation of Movement(Baseline, Week 12)
- Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Erythrocyte Sedimentation Rate(Baseline, Week 12)
- Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Childhood Health Assessment Questionnaire Disability Index (CHAQ-DI)(Baseline, Week 12)
- Part I: Percentage of Participants With Changes in Laboratory Indicators: High-sensitivity C-Reactive Protein(hsCRP), Hemoglobin (Hb), Platelets and Leukocytes From Abnormal at Baseline to Normal at Week 12(Baseline, Week 12)
- Part I: Percentage of Participants With Fever Due to Systemic Juvenile Idiopathic Arthritis (sJIA) at Baseline Who Are Free of Fever at Week 12(Baseline, Week 12)
- Part I: Percentage of Participants With Concomitant Corticosteroid Reduction(Week 6 or Week 8, Week 12)
- Part I: Change From Baseline in the Pain Visual Analog Scale (VAS) at Week 12(Baseline, Week 12)
- Part I: Percentage of Patients With Minimally Important Improvement in CHAQ-DI Score at Week 12(Baseline, Week 12)
- Part I: Percentage of Patients With Rash at Baseline Who Are Free From Rash at Week 12(Baseline, Week 12)
- Part I: Percentage of Patients With Anemia at Baseline With a ≥10 g/L Increase in Hemoglobin at Week 6 and Week 12(Baseline, Week 6 and Week 12)
- Part II: Percentage of Participants With JIA ACR70 and JIA ACR90 Responses Week 104(Baseline, Week 104)
- Part II: Number of Active Joints at Week 104(Week 104)
- Part II: Percentage of Participants With no Active Joints at Week 104(Week 104)
- Part II: Percentage of Participants With Inactive Disease at Week 104(Week 104)
- Part II: Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) Score at Week 104(Baseline, Week 104)
- Part II: Percentage of Participants With Oral Corticosteroid Cessation at Week 104(Baseline, Week 104)
- Part II: Rate of Serious Adverse Events (SAEs), Serious Infection Adverse Events (AEs), Related SAEs, Macrophage Activation Syndrome, AEs Leading to Withdrawal and Deaths Per 100 Patient Years to Week 104(104 Weeks)
- Part III: Percentage of Participants With at Least 30%, 50%, 70%, and 90% Improvement in JIA Core Set According to ACR(Weeks 104, 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248 and 260)
- Part III: Percentage of Participants Who Maintain JIA ACR30, JIA ACR50, JIA ACR70, JIA ACR90 Response for 6 Months Previous to the Specified Week(Weeks 104, 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248 and 260)
- Part III: Doses of Oral Corticosteroids(Baseline and Weeks 104, 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248 and 260)
- Part III: Percentage of Participants on Corticosteroids at Baseline Able to Discontinue Corticosteroids by Weeks 104,116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248, and 260(Weeks 104,116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248, and 260)
- Part III: Percentage of Participants With a >=20/50/75/90% Decrease From Baseline in Oral Corticosteroid Dose at Visits(Every 2 weeks from Week 104 to Week 260)
- Part III: Percentage of Participants With Inactive Disease(Weeks 104, 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260)
- Part III: Percentage of Participants in Clinical Remission(Weeks 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260)
- Part III: Percentage of Participants on Corticosteroids at Baseline in Clinical Remission Off All Oral Corticosteroids for 6 Months Prior to Specified Visits(Weeks 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260)
- Part III: Percentage of Participants on Methotrexate At Baseline in Clinical Remission Off Corticosteroids and Methotrexate for 6 Months Prior to Specified Visits(Weeks 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260)
- Part III: Percentage of Participants in Clinical Remission Off All Arthritis Medications Except Tocilizumab for 6 Months Prior to Specified Visits(Weeks 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260)
- Part III: Percentage of Participants Who Developed Antibodies To Tocilizumab During Weeks 104 to 260(Every 2 weeks from Week 104 to 260)
- Part III: Percentage of Participants Who Developed Anti-TCZ Antibodies Associated With The Occurrence of Drug Hypersensitivity Reactions.(Every 2 weeks from Week 104 to 260)