NCT05039450已完成2 期
A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Efruxifermin in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 213
- 试验地点
- 50
- 主要终点
- Main: Change from baseline in fibrosis with no worsening steatohepatitis assessed by NASH CRN system
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 cirrhotic subjects with biopsy-proven F4 compensated 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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Males and non-pregnant, non-lactating females between 18-75 years of age inclusive, based on the date of signing informed consent.
- •Main Study Only: Previous history or presence of Type 2 diabetes or 2 out of 4 components of metabolic syndrome (obesity, dyslipidemia, elevated blood pressure, elevated fasting glucose).
- •Main Study Only: Biopsy-proven compensated cirrhosis due to NASH.
- •Cohort D Only: Diagnosis of type 2 diabetes
- •Cohort D Only: Use of GLP-1R agonist for at least 90 days
- •Cohort D Only: Biopsy-proven liver fibrosis stages 1, 2, or 3
排除标准
- •Main Study Only: Weight loss > 10% in the 90 days prior to screening until randomization or from the time of collection of the liver biopsy used to assess subject eligibility until randomization, whichever is longer.
- •Type 1 diabetes or uncontrolled Type 2 diabetes
- •Cohort D Only: Weight loss > 5% in the 90 days prior to screening
- •Cohort D Only: Presence of cirrhosis on liver biopsy
- •Other inclusion and exclusion criteria may apply
研究组 & 干预措施
Placebo (Main Study)
Placebo Comparator
干预措施: Placebo (Drug)
EFX 28 mg (Main Study)
Experimental
干预措施: EFX (Drug)
EFX 50 mg (Main Study)
Experimental
干预措施: EFX (Drug)
Placebo (Cohort D)
Placebo Comparator
干预措施: Placebo (Drug)
EFX 50 mg (Cohort D)
Experimental
干预措施: EFX (Drug)
结局指标
主要结局
Main: Change from baseline in fibrosis with no worsening steatohepatitis assessed by NASH CRN system
时间窗: Week 36
Proportion of subjects who achieve ≥ 1 stage improvement in fibrosis (based on NASH CRN fibrosis score) and no worsening of steatohepatitis at Week 36.
Main: Change From Baseline in Fibrosis With no Worsening Steatohepatitis Assessed by NASH CRN System
时间窗: Week 36
Proportion of subjects who achieve ≥ 1 stage improvement in fibrosis (based on NASH CRN fibrosis score) and no worsening of steatohepatitis at Week 36. No worsening of steatohepatitis was defined as no increase in score for any of the 3 components of NAS. The evaluation of the NAS endpoint was calculated using the following 3 categorical features: steatosis \[0-3\], lobular inflammation \[0-3\], and hepatocellular ballooning \[0-2\]. NAS was derived as the unweighted sum of steatosis, lobular inflammation, and hepatocellular ballooning scores.
次要结局
- Main: Resolution of NASH assessed by the NASH CRN system(Week 36, Week 96)
- Main: Fibrosis improvement with no worsening of NASH assessed by the NASH CRN system(Week 36, Week 96)
- Main: Change from baseline in fibrosis in subjects with no worsening of steatohepatitis assessed by the NASH CRN system(Week 36, Week 96)
- Main: Change from baseline in non-invasive markers of fibrosis(Week 36, Week 48, Week 72, Week 96)
- Main: Change from baseline in lipoproteins(Week 36, Week 48, Week 72, Week 96)
- Main: Change from baseline of markers in insulin sensitivity and glycemic control(Week 36, Week 48, Week 72, Week 96)
- Main: Change from baseline in body weight(Week 36, Week 48, Week 96)
- Main: To assess the immunogenicity of EFX(Through Week 96)
- Main: To assess the safety and tolerability of EFX(Through Week 96)
- Cohort D: To assess the safety and tolerability of EFX compared to placebo when added to an existing GLP-1R agonist in subjects with type 2 diabetes and liver fibrosis due to NASH(Through Week 12)
- Main: Change From Baseline in S-Pro-C3(Week 36, Week 48, Week 72, Week 96)
- Main: Resolution of NASH Assessed by the NASH CRN System(Week 36, Week 96)
- Main: Fibrosis Improvement and Resolution of NASH Assessed by the NASH CRN System(Week 36, Week 96)
- Main: Change From Baseline in Fibrosis With no Worsening of Steatohepatitis Assessed by the NASH CRN System(Week 96)
- Main: Change From Baseline in Fibrosis by NASH CRN System(Week 36, Week 96)
- Main: Change From Baseline in Enhanced Liver Fibrosis (ELF) Score(Week 36, Week 48, Week 72, Week 96)
- Main: Change From Baseline in Liver Stiffness Assessed by Liver Elastography (kPa)(Week 36, Week 48, Week 72, Week 96)
- Main: Change From Baseline in Lipoproteins(Week 36, Week 48, Week 72, Week 96)
- Main: Change From Baseline in HbA1c (%)(Week 36, Week 48, Week 72, Week 96)
- Main: Change From Baseline in C-peptide (ug/L)(Week 36, Week 48, Week 72, Week 96)
- Main: Change From Baseline in Adiponectin (mg/L)(Week 36, Week 48, Week 72, Week 96)
- Main: Change From Baseline in Insulin (mIU/L)(Week 36, Week 48, Week 72, Week 96)
- Main: Change From Baseline in HOMA-IR(Week 36, Week 48, Week 72, Week 96)
- Main: Change From Baseline in Body Weight(Week 36, Week 48, Week 96)
- Main: Number of Participants With ADA Against EFX(Through Week 96)
- Main: To Assess the Safety and Tolerability of EFX(Through Week 96)
- Cohort D: To Assess the Safety and Tolerability of EFX Compared to Placebo When Added to an Existing GLP-1R Agonist in Subjects With Type 2 Diabetes and Liver Fibrosis Due to NASH(Through Week 12)
研究者
研究点 (50)
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