A Randomized, Double-blind, Dose-ranging, Placebo-controlled, Phase 2a Evaluation of the Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Participants With Primary Sclerosing Cholangitis (PSC) and Suspected Liver Fibrosis (INTEGRIS-PSC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 121
- 试验地点
- 60
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events
研究概览
简要总结
A Phase 2a, multicenter, randomized, double-blind, dose-ranging, placebo-controlled, study to evaluate the safety, tolerability, and PK of PLN-74809 in participants with primary sclerosing cholangitis and suspected liver fibrosis
详细描述
Three-part study:
Part 1 - 12-week treatment period evaluating 40 mg of PLN-74809 or matching placebo [Complete] Part 2 - 12-week treatment period evaluating two dose groups, 80 mg and 160 mg of PLN-74809 or matching placebo Part 3 - minimum 24-week, up to 48-week treatment period evaluating 320 mg of PLN-74809 or matching placebo
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Established clinical diagnosis of large duct PSC based on an abnormal cholangiography as assessed by magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), and/or percutaneous transhepatic cholangiopancreatography (PTC) in the context of cholestatic liver chemistry
- •Suspected liver fibrosis, as defined by liver stiffness measurement (LSM), assessed by ultrasound-based transient elastography (TE, FibroScan®) OR Enhanced Liver Fibrosis (ELF) Score OR Historical liver biopsy showing fibrosis without cirrhosis (by any scoring system) OR Magnetic resonance elastography (MRE)
- •Serum ALP concentration within normal limits or > 1 times the upper limit of normal (ULN)
- •Participants receiving treatment for IBD are allowed, if on a stable dose from screening and expected to remain stable for the duration of the study
- •Serum AST and ALT concentration ≤ 5 times the upper limit of normal
- •If receiving treatment with UDCA, therapy is at a dose of < 25 mg/kg/day, has been stable for at least 3 months before screening.
排除标准
- •Other causes of liver disease, including secondary sclerosing cholangitis or viral, metabolic, or alcoholic liver disease, as assessed clinically
- •Known or suspected overlapping clinical and histologic diagnosis of autoimmune hepatitis
- •Small duct PSC with no evidence of large duct involvement (evidence of PSC on historical liver histology, with normal bile ducts on cholangiography)
- •Presence of liver cirrhosis as assessed by liver histology, ultrasound-based liver stiffness measurement, ELF score, MRE, and/or signs and symptoms of hepatic decompensation (including but not limited to, jaundice, ascites, variceal hemorrhage, and/or hepatic encephalopathy.
- •Serum ALP concentration > 10 times the upper limit of normal.
研究组 & 干预措施
Placebo
Placebo (Part 1, 2, and 3)
干预措施: Placebo (Drug)
PLN-74809 Dose Level 1
Part 1, Cohort 1 Dose: 40 mg, up to 12 weeks
干预措施: PLN-74809 (Drug)
PLN-74809 Dose Level 2
Part 2, Cohort 2 Dose: 80 mg, up to 12 weeks; PLN-74809 Dose Level 2 following PLN-74809 Dose Level 1
干预措施: PLN-74809 (Drug)
PLN-74809 Dose Level 3
Part 2, Cohort 3 Dose: 160 mg, up to 12 weeks; PLN-74809 Dose Level 3 following PLN-74809 Dose Level 1
干预措施: PLN-74809 (Drug)
PLN-74809 Dose Level 4
Part 3, Cohort 4 Dose: 320 mg, for at least 24 weeks and up to 48 weeks; PLN-74809 Dose Level 4 following PLN-74809 Dose Levels 2 and 3
干预措施: PLN-74809 (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events
时间窗: Up to 40 weeks
Nature and proportion of TEAEs between PLN-74809 and placebo groups. Treatment-emergent adverse events (TEAEs) are defined as AEs that emerged or worsened in severity after the first administration of study drug
Number of Participants With Serious Treatment Emergent Adverse Events
时间窗: Up to 40 weeks
Nature and proportion of Serious TEAEs between PLN-74809 and placebo groups. An SAE was defined as an event that, at any dose, results in the following: death, a life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect or a medically important event or reaction.
次要结局
- Assessment of PLN-74809 Total Plasma Concentrations at Week 12(Up to 12 weeks)
- Assessment of PLN-74809 Total Plasma Concentrations at Week 24(Up to 24 weeks)