A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Selonsertib in Subjects With Nonalcoholic Steatohepatitis (NASH) and Bridging (F3) Fibrosis
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 808
- 试验地点
- 290
- 主要终点
- Event-Free Survival (EFS) at Week 240 as Assessed by Time to First Clinical Event
研究概览
简要总结
The primary objective of this study is to evaluate whether selonsertib (SEL; GS-4997) can cause fibrosis regression and reduce progression to cirrhosis and associated complications in adults with NASH and bridging (F3) fibrosis.
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, Care Provider)
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
- •Liver biopsy consistent with NASH and bridging (F3 fibrosis) according to the NASH Clinical Research Network (CRN) classification in the opinion of the central reader
- •Has the following laboratory parameters at the screening visit:
- •Alanine aminotransferase (ALT) ≤ 8 x upper limit of normal (ULN)
- •Creatinine Clearance (CLcr) ≥ 30 milliliter/minute (mL/min), as calculated by the Cockcroft-Gault equation
- •Hemoglobin A1c (HbA1c) ≤ 9.5% (or serum fructosamine ≤ 381 μmol if HbA1c is unable to be resulted)
- •Total bilirubin ≤ 1.3 x ULN (unless an alternate etiology such as Gilbert's syndrome or hemolytic anemia is present)
排除标准
- •Prior history of decompensated liver disease including clinical ascites, hepatic encephalopathy (HE), or variceal bleeding
- •Child-Pugh (CP) score > 6, as determined at screening, unless due to therapeutic anti-coagulation
- •Model for End-stage Liver Disease (MELD) score > 12, as determined at screening, unless due to therapeutic anti-coagulation
- •Other causes of liver disease including, but not limited to, alcoholic liver disease, hepatitis B, hepatitis C, autoimmune disorders, drug-induced hepatotoxicity, Wilson disease, iron overload, and alpha-1-antitryspin deficiency, based on medical history and/ or centralized review of liver histology.
- •History of liver transplantation
- •Current or history of hepatocellular carcinoma (HCC)
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
SEL 6 mg
Randomized Phase: SEL 6 mg tablet + placebo to match SEL 18 mg tablet for 240 weeks
OL Phase: Participants who experience a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, will be offered the option to roll over into an OL phase to receive OL SEL 18 mg for a total treatment duration of 240 weeks inclusive of the randomized phase.
干预措施: Placebo to match SEL 18 mg (Drug)
SEL 18 mg
Randomized Phase: Selonsertib (SEL) 18 mg tablet + placebo to match SEL 6 mg tablet for 240 weeks
Open-Label (OL) Phase: Participants who experience a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, will be offered the option to roll over into an OL phase to receive OL SEL 18 mg for a total treatment duration of 240 weeks inclusive of the randomized phase.
干预措施: SEL (Drug)
SEL 18 mg
Randomized Phase: Selonsertib (SEL) 18 mg tablet + placebo to match SEL 6 mg tablet for 240 weeks
Open-Label (OL) Phase: Participants who experience a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, will be offered the option to roll over into an OL phase to receive OL SEL 18 mg for a total treatment duration of 240 weeks inclusive of the randomized phase.
干预措施: Placebo to match SEL 6 mg (Drug)
SEL 6 mg
Randomized Phase: SEL 6 mg tablet + placebo to match SEL 18 mg tablet for 240 weeks
OL Phase: Participants who experience a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, will be offered the option to roll over into an OL phase to receive OL SEL 18 mg for a total treatment duration of 240 weeks inclusive of the randomized phase.
干预措施: SEL (Drug)
Placebo
Randomized Phase: Placebo to match SEL 6 mg tablet + placebo to match SEL 18 mg tablet for 240 weeks
OL Phase: Participants who experience a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, will be offered the option to roll over into an OL phase to receive OL SEL 18 mg for a total treatment duration of 240 weeks inclusive of the randomized phase.
干预措施: Placebo to match SEL 6 mg (Drug)
Placebo
Randomized Phase: Placebo to match SEL 6 mg tablet + placebo to match SEL 18 mg tablet for 240 weeks
OL Phase: Participants who experience a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, will be offered the option to roll over into an OL phase to receive OL SEL 18 mg for a total treatment duration of 240 weeks inclusive of the randomized phase.
干预措施: Placebo to match SEL 18 mg (Drug)
结局指标
主要结局
Event-Free Survival (EFS) at Week 240 as Assessed by Time to First Clinical Event
时间窗: Week 240
EFS was assessed by the time to the first clinical event, including progression to cirrhosis on liver biopsy, liver decompensation events, liver transplantation, and all-cause mortality.
Percentage of Participants Who Achieved a ≥ 1-Stage Improvement in Fibrosis According to the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network (CRN) Classification 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 CRN classification. NASH CRN fibrosis stages range from 0 to 4, with higher scores indicating greater fibrosis (0=None, 4=Cirrhosis). Worsening of NASH was defined as ≥ 1 point increase from baseline in hepatocellular ballooning or lobular inflammation according to the Non-Alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) criteria. As defined by NAS, hepatocellular ballooning ranges from 0-2 and lobular inflammation ranges from 0-3, with higher scores indicating more severe hepatocellular ballooning or lobular inflammation.
次要结局
- Percentage of Participants Who Had a ≥ 1-Stage Improvement in Fibrosis at Week 48(Week 48)
- Percentage of Participants Who Had Progression to Cirrhosis at Week 48(Week 48)
- Percentage of Participants Who Had a ≥ 1-Stage Improvement in Fibrosis at Week 240(Week 240)
- Percentage of Participants Who Had a ≥ 1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 240(Week 240)
- Percentage of Participants Who Had NASH Resolution Without Worsening of Fibrosis at Week 48(Week 48)
- Percentage of Participants Who Had NASH Resolution Without Worsening of Fibrosis at Week 240(Week 240)