A Multicenter, Randomized, Controlled, Open-label, Rater-blinded Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of ALXN1840 Versus Standard of Care in Pediatric Participants With Wilson Disease
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Percent Change From Baseline to Week 48 in Non-ceruloplasmin-bound Copper in Plasma
研究概览
简要总结
This study is being conducted to evaluate the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics of ALXN1840 versus standard of care in pediatric participants with Wilson disease (WD).
详细描述
Participants who complete the 48 weeks of treatment in Period 1 will have the option to receive ALXN1840 for 24 weeks in Period 2 (open-label extension).
Safety will be monitored 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
- Single (Outcomes Assessor)
盲法说明
This study is rater-blinded for the Unified Wilson Disease Rating Scale (UWDRS) assessment only.
入排标准
- 年龄范围
- 3 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Wilson Disease by Leipzig Score ≥
- •Adequate venous access to allow collection of required blood samples.
- •Able to swallow intact ALXN1840 tablets or mini-tablets.
- •Willing to avoid intake of foods and drinks with high contents of copper.
- •Willing and able to follow protocol-specified contraception requirements.
排除标准
- •Decompensated hepatic cirrhosis or MELD score > 13 (ages 12 to <18) or PELD score > 13 (ages 3 to < 12).
- •Modified Nazer score >
- •Clinically significant gastrointestinal bleed within past 3 months.
- •Alanine aminotransferase (ALT) > 2 × upper limit of normal (ULN) for participants treated for > 28 days with WD therapy or ALT > 5 × ULN for treatment-naïve participants or participants who have been treated for ≤ 28 days.
- •Marked neurological disease requiring either nasogastric feeding tube or intensive inpatient medical care.
- •Hemoglobin less than lower limit of the reference range for age and sex.
- •History of seizure activity within 6 months prior to informed consent/assent.
- •Participants in renal failure, defined as in end-stage renal disease on dialysis (chronic kidney disease stage 5) or estimated glomerular filtration rate < 30 milliliters/minute/1.73 meter squared.
研究组 & 干预措施
ALXN1840
ALXN1840 will be administered at one of two starting doses, with incremental dose increases permitted.
干预措施: ALXN1840 (Drug)
Standard of Care
Participants will receive their current therapy or initiate Standard of Care therapy.
干预措施: Standard of Care (Drug)
结局指标
主要结局
Percent Change From Baseline to Week 48 in Non-ceruloplasmin-bound Copper in Plasma
时间窗: Baseline, Week 48
Plasma samples were planned to be collected to measure ceruloplasmin-bound copper. Due to the early termination of the study, data for this Outcome Measure were not collected for any of the cohorts.
次要结局
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Primary Evaluation Period(Baseline up to Week 48)
- Area Under the Effect Versus Time Curve (AUEC) for Plasma Total Copper and Direct NCC(Week 48)
- Maximum Observed Concentration (Cmax) of ALXN1840 for Plasma Total Molybdenum and Plasma Ultrafiltrate Molybdenum Concentrations(Week 48)
- Area Under the Plasma Concentration Versus Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) of ALXN1840 for Plasma Total Molybdenum and Plasma Ultrafiltrate Molybdenum(Week 48)