A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Efruxifermin in Subjects With Non-Cirrhotic Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,650
- 试验地点
- 350
- 主要终点
- Event-free survival
研究概览
简要总结
This is a multi-center evaluation of efruxifermin (EFX) in a randomized, double-blind, placebo-controlled study in subjects with non-cirrhotic NASH/MASH and fibrosis stage 2 or 3 (F2 or F3).
The study will enroll subjects in two cohorts for a total samples size of 1650 subjects.
详细描述
This is a Phase 3, multi-center, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of efruxifermin (EFX) in subjects with non-cirrhotic nonalcoholic steatohepatitis (NASH)/metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis stage 2 or 3 (F2 or F3).
Approximately 1,650 subjects will be enrolled into 2 cohorts.
Cohort 1 will enroll approximately 750 subjects with biopsy-confirmed NASH/MASH and fibrosis stage F2 or F3. Subjects in Cohort 1 will undergo evaluation of histologic efficacy endpoints at Week 52.
Cohort 2 will enroll approximately 900 subjects with biopsy-confirmed fibrosis stage F3. Subjects in Cohort 2 may enroll regardless of NAFLD Activity Score (NAS). Subjects in Cohort 2 will undergo liver biopsy assessment at Week 96.
Eligible subjects will be randomized in a 1:1:1 ratio to receive:
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and non-pregnant, non-lactating females between 18 - 80 years of age inclusive, based on the date of the screening visit.
- •Previous history or presence of 2 out of 4 components of metabolic syndrome (obesity, dyslipidemia, elevated blood pressure, elevated fasting glucose) or type 2 diabetes.
- •Cohort 1: Biopsy-proven NASH/MASH. Must have had a liver biopsy obtained ≤ 180 days prior to screening with fibrosis stage 2 or 3 and a non-alcoholic fatty liver disease (NAFLD) activity score (NAS) of ≥ 4 with at least a score of 1 in each of the following NAS components:
- •Steatosis (scored 0 to 3),
- •Ballooning degeneration (scored 0 to 2), and
- •Lobular inflammation (scored 0 to 3).
- •Cohort 2: Biopsy-proven fibrosis stage
- •Must have had a liver biopsy obtained ≤ 180 days prior to screening. Subjects with NAS <4 may be enrolled and are not required to meet 1 point in each of the components of NAS.
排除标准
- •Other causes of liver disease based on medical history and/or liver histology and/or central laboratory results.
- •Presence of cirrhosis on liver biopsy (fibrosis stage 4).
- •Type 1 or uncontrolled Type 2 diabetes.
- •Other inclusion and exclusion criteria may apply.
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
EFX 50 mg
干预措施: Efruxifermin (Drug)
EFX 28 mg
干预措施: Efruxifermin (Drug)
结局指标
主要结局
Event-free survival
时间窗: 240 Weeks
Based on time from randomization to the first clinical event including evidence of disease progression, liver decompensation events, liver transplantation or eligibility for liver transplantation, and all-cause mortality.
Cohort 1 Only: Resolution of NASH/MASH and a ≥ 1 stage improvement in fibrosis
时间窗: 52 Weeks
Based on NAS (scored by 0-3 for steatosis, 0-3 for inflammation, and 0-2 for ballooning) and NASH CRN fibrosis score (scored by a fibrosis score of 0-4, where 0 = no fibrosis, 1 = perisinusoidal or periportal fibrosis, 2 = perisinusoidal and portal/periportal fibrosis, 3 = bridging fibrosis, 4 = cirrhosis)
次要结局
- Change from baseline of body weight (kg)(52 Weeks, 240 Weeks)
- To assess the safety and tolerability of EFX through the reporting of extent of exposure (weeks)(52 Weeks, 240 Weeks)
- Change from baseline of lipoproteins(52 Weeks, 240 Weeks)
- To assess the safety and tolerability of EFX through the reporting of adverse events (severity of events)(52 Weeks, 240 Weeks)
- To assess the safety and tolerability of EFX through the reporting of adverse events (frequency of events)(52 Weeks, 240 Weeks)
- To assess the safety and tolerability of EFX through the reporting of abnormal clinical laboratory tests, ECGs, ultrasounds, vital sign assessments (number of patients)(52 Weeks, 240 Weeks)
- To assess the immunogenicity of EFX through the reporting of antidrug antibodies (number of patients)(52 Weeks, 240 Weeks)
- Cohort 1 Only: Resolution of NASH/MASH and no worsening of fibrosis(52 Weeks)
- Cohort 1 Only: ≥ 1 stage improvement in fibrosis and no worsening of steatohepatitis(52 Weeks)
- Change from baseline of non-invasive markers of liver fibrosis: ELF score(52 Weeks)
- Change from baseline in non-invasive markers of liver fibrosis: ELF score(96 Weeks, 240 Weeks)
- Change from baseline of non-invasive markers of liver fibrosis: Fibroscan(52 Weeks)
- Change from baseline in non-invasive markers of liver fibrosis: ELF score components: TIMP-1, HA, PIIINP, Pro-C3(Week 240)
- Change from baseline of non-invasive markers of liver fibrosis(52 Weeks, 240 Weeks)
- Change from baseline of markers of liver injury(52 Weeks, 240 Weeks)
- Change from baseline of markers of insulin sensitivity and glycemic control(52 Weeks, 240 Weeks)