An Open-Label Multiple-Dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Upadacitinib in Pediatric Subjects With Polyarticular Course Juvenile Idiopathic Arthritis
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 124
- 试验地点
- 70
- 主要终点
- Part 1: Time to maximum observed plasma concentration (Tmax)
研究概览
简要总结
This is a study to evaluate pharmacokinetics, safety and tolerability of upadacitinib in pediatric participants with polyarticular course juvenile idiopathic arthritis. This study consists of three parts: Part 1 is multiple-cohort study that consists of two sequential multiple dose groups. Participants benefiting from the study drug with no ongoing adverse events of special interest or serious adverse events will have option to enroll in Part 2. Part 2 is open-label, long term extension study to evaluate safety and tolerability. Part 3 is an additional safety cohort to evaluate long-term safety and tolerability. Participants <18 years of age who are ongoing in Parts 2 and 3 will participate in an 104 week open-label extension of the study in Part 4.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Participant have total body weight of 10 kg or higher at the time of screening.
- •Participant diagnosed with pcJIA (rheumatoid factor-positive or rheumatoid factor-negative polyarticular JIA, extended oligoarticular JIA, or systemic JIA with active arthritis and without active systemic features) with a history of arthritis affecting at least 5 joints within the first 6 months of disease (for extended oligoarticular JIA: <=4 joints within first 6 months of disease and >4 joints thereafter).
- •Participant have 5 or more active joints at the time of screening, defined as the presence of swollen joints (not due to deformity) or, in the absence of swelling, joints with the limitation of movement (LOM) plus pain on motion and/or tenderness with palpitation, with LOM present in at least three of the active joints.
- •If receiving methotrexate (MTX), have been taking MTX for at least 12 weeks immediately before and including Study Day 1 on a stable dose of <=20 mg/m2 for at least 8 weeks before and including Study Day 1; in addition, participants should take either folic acid or folinic acid according to local standard of care.
- •If on oral glucocorticosteroids, must have been taking oral glucocorticosteroids at a stable dose (no greater than 10 mg/day or 0.2 mg/kg/day, whatever is lower) for at least 1 week before and including Study Day 1.
排除标准
- •Participant with diagnosis of enthesitis-related arthritis (ERA) or juvenile psoriatic arthritis (JPSA).
- •Participant have prior exposure to JAK inhibitor.
研究组 & 干预措施
Participants of age group 12 to <18 years receiving dose B
Participants of age group 12 to <18 years administered with upadacitinib dose B (weight dependent) as described in the protocol.
干预措施: Upadacitinib (Drug)
Participants of age group 6 to <12 years receiving dose A
Participants of age group 6 to <12 years administered with upadacitinib dose A (weight dependent) as described in the protocol.
干预措施: Upadacitinib (Drug)
Participants of age group 12 to <18 years receiving dose A
Participants of age group 12 to <18 years administered with upadacitinib dose A (weight dependent) as described in the protocol.
干预措施: Upadacitinib (Drug)
Participants of age group 2 to <6 years receiving dose A
Participants of age group 2 to <6 years administered with upadacitinib dose A (weight dependent) as described in the protocol.
干预措施: Upadacitinib (Drug)
Participants of age group 2 to <18 years receiving dose A
Participants of age group 2 to <18 years administered with upadacitinib dose A as described in the protocol.
干预措施: Upadacitinib (Drug)
结局指标
主要结局
Part 1: Time to maximum observed plasma concentration (Tmax)
时间窗: Day 7
Tmax is defined as the time to maximum plasma concentration (Cmax) of upadacitinib.
Part 1: Maximum observed plasma concentration (Cmax)
时间窗: Day 7
Cmax is defined as the maximum observed plasma concentration for upadacitinib.
Part 1: Apparent oral clearance at steady state (CL/F)
时间窗: Day 7
Clearance is defined as the volume of plasma cleared of the drug per unit time.
Treatment Emergent Adverse Events (TEAEs)
时间窗: Up to approximately 156 weeks
Adverse Event is defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product.
Part 1: Area under plasma concentration versus time curve during a dosing interval (AUCtau)
时间窗: Day 7
The area under the plasma concentration-time curve is a method of measurement of the total exposure of a drug in plasma.
Part 1: Half-life
时间窗: Day 7
Half life of updadacitinib will be determined using non-compartmental method.
Treatment Emergent Adverse Events (TEAEs)
时间窗: Up to approximately 260 weeks
Adverse Event is defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product.
次要结局
未报告次要终点