NCT04422431已完成2 期
A Phase 2, Single-arm Pathologist-blinded 48-week Study Using Liver Biopsy Specimens to Assess Copper Concentration and Histopathologic Changes in ALXN1840-treated Patients With Wilson Disease Followed by an up to 48-weeks Extension Period
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Change From Baseline in Liver Cu Concentration at Week 48 (Treatment Period)
研究概览
简要总结
The main objective of the study is to evaluate the change in liver copper (Cu) concentration following 48 weeks of treatment with ALXN1840 in adult participants with Wilson Disease (WD) who have been previously treated for at least 1 year with standard of care (that is, trientine, penicillamine, or zinc). In the Treatment Period, efficacy and safety of ALXN1840 will be assessed at Week 48.
详细描述
Participants who complete the 48-week Treatment Period will be offered the opportunity to continue their treatment in a 48-week Extension Period that will offer additional time for evaluation of long-term efficacy and safety of ALXN1840. There will be no liver biopsies during the Extension Period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This study is only pathologist-blinded for the assessments of liver histology samples.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of WD by Leipzig Criteria ≥ 4 or by historical test results.
- •Continuous treatment for WD with penicillamine, trientine or zinc for at least 1 year prior to screening.
- •Body mass index < 30 kilograms/meter squared.
- •Able to cooperate with a percutaneous liver biopsy.
- •Willing and able to follow protocol-specified contraception requirements.
- •Capable of giving signed informed consent.
排除标准
- •Decompensated cirrhosis or Model for End Stage Liver Disease score >
- •Modified Nazer score >
- •Clinically significant gastrointestinal bleed within past 3 months.
- •Alanine aminotransferase > 2 × upper limit of normal.
- •History of bleeding abnormality or known coagulopathy, including platelet count < 100,000, and international normalized ratio for prothrombin time ≥ 1.
- •Participant unwilling to accept blood products, if required.
- •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.
- •Participants in renal failure, defined as in end-stage renal disease on dialysis (chronic kidney disease 5) or creatinine clearance < 30 milliliters/minute.
- •Lymphoma, leukemia, or any malignancy within the past 5 years.
- •Current or chronic history of liver disease not associated with WD.
研究组 & 干预措施
ALXN1840
Experimental
Participants will receive ALXN1840.
干预措施: Bis-Choline Tetrathiomolybdate (Drug)
结局指标
主要结局
Change From Baseline in Liver Cu Concentration at Week 48 (Treatment Period)
时间窗: Baseline, Week 48 (Treatment Period)
Liver biopsy samples were taken for the assessment of liver Cu concentration. Multiple imputation was used to impute missing data at Week 48 due to any reason based on Baseline values.
次要结局
- Number of Participants With Change From Baseline in Metavir Fibrosis Score at Week 48 (Treatment Period)(Baseline, Week 48 (Treatment Period))
- Change From Baseline in Hepatic Collagen Content at Week 48 (Treatment Period)(Baseline, Week 48 (Treatment Period))
- Change From Baseline in NAS Total Score at Week 48 (Treatment Period)(Baseline, Week 48 (Treatment Period))
- Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period)(Baseline, Week 48 (Treatment Period))
- Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period)(Baseline, Week 48 (Treatment Period))
- Change From Baseline in Hepatic Fat Content at Week 48 (Treatment Period)(Baseline, Week 48 (Treatment Period))
- Treatment Period: Predose Trough Plasma Total Mo Concentration(Predose up to 4 hours postdose at Week 6 (Day 43) and Week 36 (Day 253))
- Treatment Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Day 1 (Treatment Period) up to Week 48 (Treatment Period))
- Extension Period: Number of Participants With TEAEs(Day 1 (Extension Period) up Week 52 (Extension Period))
- Treatment Period: Predose Trough Plasma Total PUF Mo Concentration(Predose up to 4 hours postdose at Week 6 (Day 43) and Week 36 (Day 253))
- Change From Baseline in Mo in Liver Biopsy Specimen at Week 48 (Treatment Period)(Baseline, Week 48 (Treatment Period))
- Change From Baseline in CGI-S Scale Score at Week 48 (Treatment Period)(Baseline, Week 48 (Treatment Period))
- Change From Baseline in a-SMA Content at Week 48 (Treatment Period)(Baseline, Week 48 (Treatment Period))
- Number of Participants With Change From Baseline in NAS Steatosis Grading Score at Week 48 (Treatment Period)(Baseline, Week 48 (Treatment Period))
- Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 48 (Treatment Period)(Week 48 (Treatment Period))
研究者
研究点 (1)
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