A Phase Ib, Open-Label, Multicenter Study to Investigate the Pharmacokinetics, Pharmacodynamics, and Safety of Tocilizumab Following Subcutaneous Administration to Patients With Systemic Juvenile Idiopathic Arthritis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 42
- 主要终点
- Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Tocilizumab
研究概览
简要总结
This open-label, multicenter study will evaluate the pharmacokinetics, pharmacodynamics, and safety of subcutaneously administered tocilizumab in participants with Systemic Juvenile Idiopathic Arthritis (sJIA). Participants with body weight less than (<) 30 kilograms (kg) will receive subcutaneous (SC) tocilizumab dose every 2 weeks (Q2W) and participants with body weight greater than or equal to (>=) 30 kg will receive weekly (QW), for 52 weeks. Tocilizumab was administered every 10 days until pre-planned interim analysis was performed and changed to Q2W in participants with body weight <30 kg.
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
- 1 Year 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of sJIA according to the International League of Associations for Rheumatology (ILAR) classification
- •History of inadequate clinical response (in the opinion of the treating physician) to Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and corticosteroids
- •If a participant has received previous treatment with any biologic agents other than tocilizumab, these must have been discontinued according to the timelines defined by protocol prior to the baseline visit
- •Participants currently receiving tocilizumab by the intravenous (IV) route of administration and with well-controlled disease do not require a period of discontinuation of IV tocilizumab and should have their first dose of SC tocilizumab administered on the date that their next IV tocilizumab infusion would be due
- •Concurrent treatment with Disease Modifying Anti-Rheumatic Drugs (DMARDs) including methotrexate (MTX), NSAIDs, and oral corticosteroids are permitted at the discretion of the investigator
- •Participants of reproductive potential must be willing to use highly effective contraceptive methods
排除标准
- •Prior discontinuation of IV tocilizumab because of inadequate clinical response or safety events (including hypersensitivity)
- •Participants with poorly controlled disease (in the opinion of the treating physician) despite current treatment with IV tocilizumab
- •sJIA that is well controlled by any treatment agent other than tocilizumab (Juvenile Arthritis Disease Activity Score of 71 Joints [JADAS-71] less than or equal to [<=] 3.8 with no fever)
- •Participants who are wheelchair-bound or bedridden
- •Any other auto-immune, rheumatic disease, or overlapping syndrome other than sJIA
- •Lack of recovery from recent surgery or an interval of <6 weeks since surgery at the time of the screening visit
- •Females who are pregnant, lactating, or intending to become pregnant during study conduct
- •Any significant concurrent medical or surgical condition that would jeopardize the participant's safety or ability to complete the study
- •Known Human Immunodeficiency Virus (HIV) infection or other acquired forms of immune compromise or inborn conditions characterized by a compromised immune system
- •History of alcohol, drug, or chemical abuse within 6 months of screening
- •Any active acute, subacute, chronic, or recurrent bacterial, viral, or systemic fungal infection or any major episode of infection requiring hospitalization or treatment during screening or treatment with IV antibiotics completed within 4 weeks of the screening visit or oral antibiotics completed within 2 weeks of the screening visit
- •History of atypical tuberculosis (TB) or active TB requiring treatment within 2 years prior to screening visit
- •Positive TB test at screening unless treated with anti-TB therapy for at least 4 weeks prior to receiving study drug
- •History of reactivation or new onset of a systemic infection such as herpes zoster or Epstein-Barr virus within 2 months of the screening visit
- •Hepatitis B surface antigen or hepatitis C antibody positivity or chronic viral or autoimmune hepatitis
- •History of concurrent serious gastrointestinal disorders such as ulcer or inflammatory bowel disease, Crohn's disease, ulcerative colitis, or other symptomatic lower gastrointestinal conditions
- •History of or current cancer or lymphoma
- •Uncontrolled diabetes mellitus with elevated glycosylated hemoglobin
- •Macrophage activation syndrome (MAS) within 3 months of the screening visit
- •Inadequate hematologic, renal or liver function
研究组 & 干预措施
Tocilizumab
Participants will receive SC dose of tocilizumab based on body weight; participants with <30 kg will receive 162 milligrams (mg) of tocilizumab Q2W and those participants =>30 kg will receive 162 mg of tocilizumab QW, for 52 weeks.
干预措施: Tocilizumab (Drug)
结局指标
主要结局
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Tocilizumab
时间窗: Age <2 years: 0 hours(h) on Days(D) 0,84; on D5,14,42,70,85,88,98,182,266, 364. Weight <30kg, Age>=2 years: 0,6,12h on D0,84; on D2,5,14,42,56,70,86,87,88,90,98,182,266,364. Weight >=30kg: 0,6,12h on D0, 91; on D2,4,7,14,28,56,92,93,95,96,98,182,266, 364
Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Tocilizumab
时间窗: Age <2 years: 0h on D0,84; on D5,14,42,70,85,88,98,182,266,364. Weight <30 kg, Age >=2 years: 0,6,12h on D0,84; on D2,5,14,42,56,70,86,87,88,90,98,182,266,364. Weight >=30 kg: 0,6,12h on D0, 91; on D2,4,7,14,28,56,92,93,95,96,98,182,266,364
Pharmacokinetics: Minimum Plasma Concentration (Cmin) of Tocilizumab
时间窗: Weight <30 kg: predose (0h) on Days 0 and 84. Weight >= 30 kg: predose (0h) on Days 0 and 91
次要结局
- Pharmacodynamics: Soluble IL-6 Receptor (sIL-6R) Levels(Age<2 years: 0h on Days 0,84; Days 5,14,42,70,85,88,98,182,266,364. Weight <30 kg, Age >=2 years: 0,6,12h on Days 0,84; Days 2,5,14,42,56,70,86,87,88,90,98,182,266,364. Weight >=30kg: 0,6,12h on Days 0,91;Days 2,4,7,14,28,56,92,93,95,96,98,182,266,364)
- Pharmacodynamics: Serum Interleukin-6 (IL6) Levels(Age<2 years: 0h on Days 0,84; Days 5,14,42,70,85,88,98,182,266,364. Weight <30 kg, Age >=2 years: 0,6,12h on Days 0,84; Days 2,5,14,42,56,70,86,87,88,90,98,182,266,364. Weight >=30kg: 0,6,12h on Days 0,91;Days 2,4,7,14,28,56,92,93,95,96,98,182,266,364)
- Pharmacodynamics: Serum C-Reactive Protein (CRP) Levels(Age <2years: Days 0,14,28,42,70,84,98,126, 154,182,210,238,266,294,322,350,364. Weight <30 kg, Age >=2years: Days 0,14,28,42,70, 98,126,154,182,210,238,266,294,322,350,364. Weight >=30kg: Days 0,7,14,21,28,42, 56,70,84,91,95,96,98,182,266,294,322,350,364)
- Pharmacodynamics: Serum Erythrocyte Sedimentation Rate (ESR)(Age <2years: Days 0,14,28,42,70,84,98,126, 154,182,210,238,266,294,322,350,364. Weight <30 kg, Age >=2years: Days 0,14,28,42,70, 98,126,154,182,210,238,266,294,322,350,364. Weight >=30kg: Days 0,7,14,21,28,42, 56,70,84,91,95,96,98,182,266,294,322,350,364)
- Pharmacodynamics: Percentage of Participants with Anti-Tocilizumab Antibodies(Age <2 years: Days 0, 84, 182, 266, 364. Weight <30 kg, Age >=2 years: Days 0, 84, 182, 266, 364. Weight >=30 kg: Days 0, 91, 182, 266, 364)
- Safety: Percentage of Participants with At Least 1 Adverse Event(57 weeks)