A Phase 3, Two-part, Double-blind, Randomized, Placebo-controlled Study to Investigate the Safety and Efficacy of Efimosfermin Alfa Injection in Adult Participants With Compensated Cirrhosis (Stage F4 Fibrosis) Due to Metabolic Dysfunction-associated Steatohepatitis (NEBULA-2)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 380
- 试验地点
- 15
- 主要终点
- Part A: Proportion of participants achieving improvement in liver fibrosis by >=1 stage and no worsening of MASH
研究概览
简要总结
This is a multi-center, randomized, two-part (Part A and Part B) study investigating the safety and efficacy of efimosfermin alfa in adult participants with compensated cirrhosis due to MASH. Participants who complete the treatment during Part A of the study and meet the inclusion criteria will have the option to enroll in Part B (open label) of the study.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
The Part A of study is a double-blind study
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
- •Participants aged between 18 and 75 years at enrolment.
- •Participants with history or presence of at least two components of metabolic syndrome.
- •Liver biopsy consistent with cirrhosis (fibrosis stage 4).
排除标准
- •Participants with other chronic liver diseases.
- •Participants with evidence or history of decompensated liver disease or hepatocellular carcinoma.
- •Participants with history of Type 1 diabetes mellitus; or major Type 2 diabetes mellitus complications.
- •History or evidence of chronic pancreatic disease; pancreatic injury or acute pancreatitis within 6 months before Screening.
- •A recent history or planned surgical procedures or medications intended to produce significant weight loss.
- •Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) >= 5 times upper limit normal (ULN).
- •Current or history of excessive alcohol intake
研究组 & 干预措施
Part A: Participants receiving Efimosfermin alfa
Participants will receive efimosfermin alfa in Part A of the study.
干预措施: Efimosfermin alfa (Drug)
Part A: Participants receiving Placebo
Participants will receive placebo in Part A of the study.
干预措施: Placebo (Drug)
Part B: Participants receiving Efimosfermin alfa
All participants will receive efimosfermin alfa in Part B of the study.
干预措施: Efimosfermin alfa (Drug)
结局指标
主要结局
Part A: Proportion of participants achieving improvement in liver fibrosis by >=1 stage and no worsening of MASH
时间窗: At Week 96
Participants experiencing improvement in liver fibrosis of \>=1 stage (based on MASH Clinical Research Network (CRN) fibrosis score) and no worsening of MASH (defined as no increase in nonalcoholic fatty liver disease activity score for ballooning, inflammation, or steatosis). MASH CRN fibrosis score ranges from 0 to 4, higher score indicates greater severity.
次要结局
- Part A: Proportion of participants with Treatment-Emergent Adverse Events (TEAEs) and TEAEs by severity(Week 96)
- Part A: Proportion of participants with TEAEs leading to discontinuation and TEAEs leading to discontinuation by severity(Week 96)
- Part A: Proportion of participants with Grade 3 and Grade 4 laboratory abnormalities(Week 96)
- Part A: Proportion of participants achieving change from Baseline in vibration-controlled transient elastography (VCTE)- liver stiffness measurement (LSM) and in enhanced liver fibrosis (ELF) score(Baseline (Day 1) and Week 96)
- Part A Change from Baseline in VCTE-LSM(Baseline (Day 1) and Week 96)