A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Efficacy of Cilofexor in Non-Cirrhotic Subjects With Primary Sclerosing Cholangitis
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 419
- 试验地点
- 201
- 主要终点
- Percentage of Participants With Progression of Liver Fibrosis at Blinded Phase Week 96
研究概览
简要总结
The primary objective of this study is to evaluate whether cilofexor reduces the risk of fibrosis progression among non-cirrhotic adults with primary sclerosing cholangitis (PSC).
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
- Double (Participant, Investigator)
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
- •Diagnosis of large duct PSC
- •Liver biopsy at screening that is deemed acceptable for interpretation and demonstrates stage F0 - F3 fibrosis in the opinion of the central reader
- •Individual has the following laboratory parameters at the screening visit, as determined by the central laboratory:
- •Platelet count ≥ 150,000/mm^3
- •Estimated glomerular filtration rate (eGFR) ≥ 30 milliliter/minute (mL/min), as calculated by the Cockcroft-Gault equation
- •Alanine transaminase (ALT) ≤ 8 x upper limit of the normal range (ULN)
- •Total bilirubin < 2 mg/dL, unless the individual is known to have Gilbert's syndrome or hemolytic anemia
- •International normalized ratio (INR) ≤ 1.4, unless due to therapeutic anticoagulation
- •Negative anti-mitochondrial antibody
排除标准
- •Current or prior history of any of the following:
- •Cirrhosis
- •Liver transplantation
- •Cholangiocarcinoma or hepatocellular carcinoma (HCC)
- •Ascending cholangitis within 30 days of screening
- •Presence of a percutaneous drain or biliary stent
- •Other causes of liver disease
- •Current or prior history of unstable cardiovascular disease
- •Current moderate to severe inflammatory bowel disease (IBD) (including ulcerative colitis, Crohn's disease, and indeterminate colitis)
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Cilofexor 100 mg (Blinded Phase)
Participants received cilofexor 100 mg tablet, orally, once daily for up to 100.3 weeks.
干预措施: Cilofexor (Drug)
Placebo (Blinded Phase)
Participants received placebo to match cilofexor 100 mg tablet, orally, once daily for up to 98.1 weeks.
干预措施: Placebo (Drug)
Cilofexor From Cilofexor 100 mg (OLE Phase)
Participants who received cilofexor in blinded phase and had entered the open-label extension (OLE) phase received open-label cilofexor 100 mg tablet, orally, once daily for up to 44.7 weeks.
干预措施: Cilofexor (Drug)
Cilofexor From Placebo (OLE Phase)
Participants who received placebo in blinded phase and had entered the OLE phase received open-label cilofexor 100 mg tablet, orally, once daily for up to 45.0 weeks.
干预措施: Cilofexor (Drug)
结局指标
主要结局
Percentage of Participants With Progression of Liver Fibrosis at Blinded Phase Week 96
时间窗: Blinded Phase Week 96
Progression of liver fibrosis was defined as having a ≥ 1-stage increase from baseline in fibrosis according to the Ludwig classification at Blinded Phase Week 96. The stages of fibrosis was assessed according to Ludwig classification. Ludwig classification fibrosis stages range from 0 to 4, with higher scores indicating greater fibrosis (0=no fibrosis, 4=cirrhosis).
次要结局
- Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) in The Blinded Phase(First dose date in the Blinded Phase up to 100.3 weeks plus 30 days)
- Percentage of Participants Who Experienced TEAEs in The OLE Phase(First dose date in the OLE Phase up to 45 weeks plus 30 days)
- Percentage of Participants Who Experienced Treatment-emergent Serious Adverse Events (SAEs) in the Blinded Phase(First dose date in the Blinded Phase up to 100.3 weeks plus 30 days)
- Percentage of Participants Who Experienced Treatment-emergent SAEs in the OLE Phase(First dose date in the OLE Phase up to 45 weeks plus 30 days)
- Change From Baseline in Serum Concentrations of Alkaline Phosphatase (ALP) at Blinded Phase Week 96(Baseline, Blinded Phase Week 96)
- Change From Baseline in Serum Concentrations of Alanine Aminotransferase (ALT) at Blinded Phase Week 96(Baseline, Blinded Phase Week 96)
- Change From Baseline in Serum Concentrations of Fasting Total Bile Acids at Blinded Phase Week 96(Baseline, Blinded Phase Week 96)
- Percentage of Participants With ≥ 25% Relative Reduction in Serum ALP Concentration From Baseline and No Worsening of Fibrosis According to the Ludwig Classification at Blinded Phase Week 96(Baseline, Blinded Phase Week 96)
- Percentage of Participants With Fibrosis Improvement According to the Ludwig Classification at Blinded Phase Week 96(Blinded Phase Week 96)
- Change From Baseline in Primary Sclerosing Cholangitis (PSC) Symptoms - Module 1 Based on Disease-specific Patient Reported Outcome (PSC-PRO) at Blinded Phase Week 96(Baseline, Blinded Phase Week 96)
- Change From Baseline in Enhanced Liver Fibrosis (ELF™ ) Test Score at Blinded Phase Week 96(Baseline, Blinded Phase Week 96)
- Change From Baseline in Liver Stiffness by FibroScan® at Blinded Phase Week 96(Baseline, Blinded Phase Week 96)