A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Selonsertib, GS-0976, GS-9674, and Combinations in Subjects With Bridging (F3) Fibrosis or Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 395
- 试验地点
- 101
- 主要终点
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
The primary objectives of this study are:
- To assess the safety and tolerability of selonsertib (SEL), firsocostat (FIR) and cilofexor (CILO), administered alone or in combination, in participants with bridging fibrosis or compensated cirrhosis due to NASH
- To evaluate changes in liver fibrosis, without worsening of NASH
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Liver biopsy consistent with NASH and F3 or F4 in the opinion of the central reader
- •In participants who have never had a liver biopsy, liver stiffness by FibroScan® ≥ 14.0 kPa and Enhanced Liver Fibrosis (ELF™) Test score ≥ 9.8 at Screening
- •Screening laboratory parameters, as determined by the central laboratory:
- •Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, as calculated by the Cockcroft-Gault equation
- •Hemoglobin A1c (HbA1c) ≤ 9.5%
- •Alanine aminotransferase (ALT) < 5 x Upper Limits of Normal (ULN)
- •Platelet count ≥ 125,000/μL
排除标准
- •Prior history of decompensated liver disease including ascites, hepatic encephalopathy, or variceal bleeding
- •Child-Pugh (CP) score > 6 at Screening, unless due to an alternative etiology such as Gilbert's syndrome or therapeutic anticoagulation
- •Model for End-Stage Liver Disease (MELD) score > 12 at Screening, unless due to an alternate etiology such as therapeutic anticoagulation
- •Other causes of liver disease based on medical history and/or centralized review of liver histology, including but not limited to: alcoholic liver disease, hepatitis B, hepatitis C, autoimmune disorders (eg, primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1-antitrypsin deficiency requiring treatment
- •History of liver transplantation
- •Current or prior history of hepatocellular carcinoma
- •Note: Other protocol defined Inclusion/ Exclusion criteria may apply
研究组 & 干预措施
Selonsertib (SEL)
Participants will receive SEL + placebo to match firsocostat 20 mg tablet + placebo to match cilofexor 30 mg tablet orally once daily for 48 weeks.
干预措施: SEL (Drug)
Selonsertib (SEL)
Participants will receive SEL + placebo to match firsocostat 20 mg tablet + placebo to match cilofexor 30 mg tablet orally once daily for 48 weeks.
干预措施: Placebo to match FIR (Drug)
Selonsertib (SEL)
Participants will receive SEL + placebo to match firsocostat 20 mg tablet + placebo to match cilofexor 30 mg tablet orally once daily for 48 weeks.
干预措施: Placebo to match CILO (Drug)
Firsocostat (FIR)
Participants will receive placebo to match SEL 18 mg tablet + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.
干预措施: FIR (Drug)
Firsocostat (FIR)
Participants will receive placebo to match SEL 18 mg tablet + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.
干预措施: Placebo to match CILO (Drug)
Firsocostat (FIR)
Participants will receive placebo to match SEL 18 mg tablet + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.
干预措施: Placebo to match SEL (Drug)
Cilofexor (CILO)
Participants will receive placebo to match SEL 18 mg tablet + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks.
干预措施: CILO (Drug)
Cilofexor (CILO)
Participants will receive placebo to match SEL 18 mg tablet + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks.
干预措施: Placebo to match FIR (Drug)
Cilofexor (CILO)
Participants will receive placebo to match SEL 18 mg tablet + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks.
干预措施: Placebo to match SEL (Drug)
Selonsertib (SEL) + Firsocostat (FIR)
Participants will receive SEL + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.
干预措施: SEL (Drug)
Selonsertib (SEL) + Firsocostat (FIR)
Participants will receive SEL + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.
干预措施: FIR (Drug)
Selonsertib (SEL) + Firsocostat (FIR)
Participants will receive SEL + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.
干预措施: Placebo to match CILO (Drug)
Placebo
Participants will receive placebo to match SEL 18 mg + placebo to match FIR 20 mg tablet + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.
干预措施: Placebo to match CILO (Drug)
Selonsertib (SEL) + Cilofexor (CILO)
Participants will receive SEL + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks.
干预措施: SEL (Drug)
Selonsertib (SEL) + Cilofexor (CILO)
Participants will receive SEL + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks.
干预措施: CILO (Drug)
Selonsertib (SEL) + Cilofexor (CILO)
Participants will receive SEL + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks.
干预措施: Placebo to match FIR (Drug)
Firsocostat (FIR) + Cilofexor (CILO)
Participants will receive placebo to match SEL 18 mg tablet + FIR + CILO orally once daily for 48 weeks.
干预措施: FIR (Drug)
Firsocostat (FIR) + Cilofexor (CILO)
Participants will receive placebo to match SEL 18 mg tablet + FIR + CILO orally once daily for 48 weeks.
干预措施: CILO (Drug)
Firsocostat (FIR) + Cilofexor (CILO)
Participants will receive placebo to match SEL 18 mg tablet + FIR + CILO orally once daily for 48 weeks.
干预措施: Placebo to match SEL (Drug)
Placebo
Participants will receive placebo to match SEL 18 mg + placebo to match FIR 20 mg tablet + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.
干预措施: Placebo to match FIR (Drug)
Placebo
Participants will receive placebo to match SEL 18 mg + placebo to match FIR 20 mg tablet + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.
干预措施: Placebo to match SEL (Drug)
结局指标
主要结局
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
时间窗: First dose date up to 48 weeks plus 30 days
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
时间窗: First dose date up to 48 weeks plus 30 days
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. Participants with any laboratory abnormality were reported.
Percentage of Participants Who Achieved a ≥ 1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 48
时间窗: Week 48
Fibrosis improvement was defined as ≥ 1-stage decrease from baseline in fibrosis according to the NASH clinical research network classification (CRN) classification. Worsening of NASH was defined as ≥ 1-point increase from baseline in hepatocellular ballooning or lobular inflammation. The 95% CI was based on the Clopper-Pearson method.
次要结局
未报告次要终点