Long-Term Low-Intervention SafEty and Clinical Outcomes Clinical Study of LivmArli® in Patients With Alagille Syndrome or Progressive Familial Intrahepatic Cholestasis in the European Union (LEAP-EU)
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 230
- 试验地点
- 28
- 主要终点
- Liver function tests (LFTs) - measuring enzyme activity or concentration
研究概览
简要总结
In patients with Alagille syndrome (ALGS), the key objectives are to evaluate the tolerability, long-term safety (including possible liver toxicity) and long-term efficacy of Livmarli treatment.
In patients with Progressive Familial Intrahepatic Cholestasis (PFIC), the key objectives are to evaluate tolerability, long-term safety (including possible liver toxicity and potential impact of chronic exposure to propylene glycol (PG)), long-term efficacy, and growth and development.
详细描述
This is a multicenter, open-label, low-intervention clinical study in participants diagnosed with either ALGS with cholestatic pruritus or PFIC who are treated with Livmarli.
Participants will be treated according to standard of care for the duration of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 2 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Understand and execute an Informed consent and assent (as applicable)
- •For participants with ALGS ≥2 months of age at Day 1
- •For participants with PFIC, ≥3 months of age at Day 1
- •A clinically and/or genetically confirmed ALGS diagnosis with pruritus secondary to chronic cholestasis, or a clinically and/or genetically confirmed PFIC diagnosis
- •For the ALGS primary cohort: Initiation of Livmarli at the time of study entry
- •For the ALGS supplemental cohort, : Actively using Livmarli prior to study entry
- •For participants with PFIC: Prescribed Livmarli at the time of study entry or prior to study entry
排除标准
- •History of Liver Transplant
- •Any Livmarli contraindications (as per SmPC)
- •Any condition or abnormality that, in the opinion of the investigator, may interfere with the participation in or completion of the study
- •Received an investigational drug within 30 days before the first dose of Livmarli (Participation in previous maralixibat studies or expanded-access programs is acceptable.)
- •Received another IBAT inhibitor within 7 days before the first dose of Livmarli
- •Baseline data before start of treatment of Livmarli are unavailable (<2 values before treatment) for key safety (LFTs, FSV laboratory results) and key efficacy (sBA, pruritus) parameter
研究组 & 干预措施
Livmarli
ALGS: Primary cohort with a minimum of 45 previously untreated (treatment naïve). Supplemental cohort of participants who have previously received Livmarli.
PFIC: Patients with Progressive Familial Intrahepatic Cholestasis treated with Livmarli. The study will enroll a minimum of 130 patients with PFIC
干预措施: Livmarli Oral Product (Drug)
结局指标
主要结局
Liver function tests (LFTs) - measuring enzyme activity or concentration
时间窗: Once every 3-4 months, for 5 years.
Change in LFTs from Baseline: Total and direct bilirubin
Adverse Events (AEs)
时间窗: Up to 7 days after the last dose of Livmarli.
Number and proportion of participants with AEs.
Fat-Soluble Vitamins (FSV) Concentration
时间窗: Once every 3-4 months, for 5 years.
Change in FSV levels (vitamins A, D, and E) from Baseline.
International Normalized Ratio (INR)
时间窗: Once every 3-4 months, for 5 years.
Change in INR level from Baseline.
Long-Term Clinical Outcomes
时间窗: Once every 3-4 months, for 5 years.
Number of participants with surgical biliary diversion, liver transplantation, liver transplant waitlist status change, clinically evident portal hypertension, complications of liver cirrhosis, liver carcinoma, liver decompensation, and death.
次要结局
未报告次要终点