A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Efficacy of GS-9674 in Subjects With Primary Biliary Cholangitis Without Cirrhosis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 71
- 主要终点
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) in the Blinded Study Phase
研究概览
简要总结
The primary objective of this study is to evaluate the safety and tolerability of cilofexor in adults with primary biliary cholangitis (PBC).
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meets all of the following conditions
- •Definite or probable PBC as defined by at least 2 of the 3 following criteria:
- •Serum alkaline phosphatase (ALP) > the upper limit of normal (ULN)
- •Presence of anti-mitochondrial antibodies (AMA) in serum (≥ 1:40 on immunofluorescence)
- •Liver histological findings consistent with PBC including nonsuppurative, destructive cholangitis affecting mainly the interlobular bile and septal bile ducts
- •Serum ALP > 1.67 x ULN and/or total bilirubin >ULN but ≤ 2 x ULN
- •Ursodeoxycholic acid (UDCA) use at a stable dose for at least 12 months or intolerant of UDCA with no UDCA use for at least 12 months before screening
- •Screening FibroSURE/FibroTest® < 0.75 unless a historical liver biopsy within 12 months of screening does not reveal cirrhosis. In adults with Gilbert's syndrome or hemolysis, FibroSURE/FibroTest will be calculated using direct bilirubin instead of total bilirubin.
排除标准
- •Alanine aminotransferase (ALT) > 5 x ULN
- •Total bilirubin > 2 x ULN
- •International normalized ratio (INR) > 1.2 unless on anticoagulant therapy
- •Other causes of liver disease including viral, metabolic, alcoholic, and other autoimmune conditions. Participants with hepatic steatosis may be included if there is no evidence of nonalcoholic steatohepatitis (NASH) in the opinion of the investigator or on liver biopsy.
- •Use of fibrates or obeticholic acid within 3 months prior to screening through the end of treatment
- •Cirrhosis of the liver as defined by any of the following:
- •Historical liver biopsy demonstrating cirrhosis (eg, Ludwig stage 4 or Ishak stage ≥ 5)
- •History of decompensated liver disease, including ascites, hepatic encephalopathy or variceal bleeding
- •Liver stiffness > 16.9 kPa by FibroScan®
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Cilofexor 30 mg (Blinded Study Phase)
Cilofexor 30 mg + placebo to match cilofexor 100 mg for 12 weeks.
干预措施: Cilofexor (Drug)
Cilofexor 30 mg (Blinded Study Phase)
Cilofexor 30 mg + placebo to match cilofexor 100 mg for 12 weeks.
干预措施: Placebo to match cilofexor (Drug)
Cilofexor 100 mg (Blinded Study Phase)
Cilofexor 100 mg + placebo to match cilofexor 30 mg for 12 weeks.
干预措施: Cilofexor (Drug)
Cilofexor 100 mg (Blinded Study Phase)
Cilofexor 100 mg + placebo to match cilofexor 30 mg for 12 weeks.
干预措施: Placebo to match cilofexor (Drug)
Placebo (Blinded Study Phase)
Placebo to match cilofexor 30 mg + placebo to match cilofexor 100 mg for 12 weeks.
干预措施: Placebo to match cilofexor (Drug)
Cilofexor (Open Label Extension Phase)
Following the Blinded Study Phase, eligible participants may have the option to receive open-label cilofexor 100 mg for an additional 96 weeks.
干预措施: Cilofexor (Drug)
结局指标
主要结局
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) in the Blinded Study Phase
时间窗: First dose date up to Week 12 + 30 days
Percentage of Participants Who Experienced Graded Laboratory Abnormalities in the OLE Phase
时间窗: First dose date in the OLE phase up to last dose date (Maximum: 97.4 weeks) + 30 days
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant.
Percentage of Participants Experiencing TEAEs and TESAEs in the Open-Label Extension (OLE) Phase
时间窗: First dose date in the OLE phase up to last dose date (Maximum: 97.4 weeks) + 30 days
Percentage of Participants Who Experienced Graded Laboratory Abnormalities in the Blinded Study Phase
时间窗: First dose date up to Week 12 + 30 days
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant.
次要结局
未报告次要终点