A Phase 3 Study to Evaluate the Efficacy and Safety of Pegozafermin in Subjects with Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 89bio, Inc.
- 入组人数
- 1,050
- 试验地点
- 9
- 主要终点
- Proportion if participants with at least an improvement of Fibrosis greater than equal to 1 stage without worsening of MASH or NASH at week 52
研究概览
简要总结
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study of pegozafermin for the treatment of liver fibrosis stage F2 or F3 in adult subjects with MASH.
The study is designed to assess the efficacy and safety of 2 dose regimens of pegozafermin, administered either weekly (QW) or once every 2 weeks (Q2W) in subjects with biopsy-confirmed NASH (NASH Clinical Research Network [CRN] system: F2 and F3) as further defined in the groups below.
The study will enroll subjects in 2 groups:
(1) Group A: Subjects with F2 or F3 fibrosis and a NAS greater than equal to 4 with a score of at least 1 in each of steatosis, ballooning degeneration, and lobular inflammation. Group A will comprise approximately 840 subjects.
(2) Group B: Subjects who do not meet NAS criteria for group A and have F3 fibrosis and a score of at least 1 in steatosis. Group B will comprise approximately 210 subjects.
Pegozafermin is a glycoPEGylated (PEG; polyethylene glycol) analog of fibroblast growth factor 21 (FGF21). FGF21 is a member of the fibroblast growth factor (FGF) endocrine subfamily and contributes to the regulation of glucose and lipid metabolism. FGF21 increases adipose and hepatic insulin sensitivity, suppresses lipolysis and non-esterified fatty acid (NEFA) release from adipocytes, and reduces serum NEFA and liver triglyceride (TG) levels
This study will assess the effect of pegozafermin on the histological surrogate endpoints at Interim Analysis (IA) at 52 weeks, and clinical outcome at the event-driven.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Double
入排标准
- 年龄范围
- 18.00 Year(s) 至 80.00 Year(s)（—）
- 性别
- All
入选标准
- •Males or non-pregnant females aged between 18 and 80 years (inclusive) at time of signing the informed consent form (ICF) -Biopsy-confirmed MASH (previously named NASH) either through a historical biopsy or a biopsy at Screening in a.
- •Group A Subjects with fibrosis stage F2 or F3 per NASH CRN system and NAS greater than or equal to 4, with a score of at least 1 in each of steatosis, ballooning degeneration, and lobular inflammation.
- •Group B Subjects who do not meet NAS criteria for Group A and have F3 fibrosis and a score of at least 1 in steatosis.
- •This will include subjects with NAS less than 4 and or a ballooning degradation score of
- •A historical biopsy obtained within 6 months prior to first day of Screening (i.e., day ICF is signed) is acceptable if it is deemed suitable for interpretation and study-eligible by a central-read consensus and if the subject has had no significant change in metabolic status (control of diabetes, hyperlipidemia, or greater than 5 percent weight loss or gain).
- •Body mass index (BMI) at Screening greater than or equal to 25.0 kg per m2 (greater than or equal to 23.0 kg per m2 for Asian countries).
排除标准
- •Chronic liver diseases other than MASH -Evidence of cirrhosis (NASH CRN fibrosis stage F4 on screening biopsy assessed by central read) -Uncontrolled or newly diagnosed (less than or equal to 3 months since diagnosis) type 2 diabetes mellitus (T2DM).
- •a.Hemoglobin A1c (HbA1c) level greater than 9.5 percent at Screening.
- •b.Subjects who are on antidiabetic medications must be on a continuous regimen for greater than or equal to 3 months prior to Screening (6 months of a continuous regimen for glucagon-like peptide 1 (GLP-1) based therapies including GLP-1 agonists, GLP-1 or glucose-dependent insulinotropic polypeptide [GIP] dual agonists, and other GLP-1 combination treatments) c.See Section 5.2 for further details on exclusion criterion.
- •Type 1 diabetes mellitus -Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than or equal to 250 Unit per litre The full list with details of eligibility criteria is provided in Section 5 of Protocol.
结局指标
主要结局
Proportion if participants with at least an improvement of Fibrosis greater than equal to 1 stage without worsening of MASH or NASH at week 52
时间窗: week 52
Proportion if participants with MASH or NASH resolution without worsening of fibrosis at week 52
时间窗: week 52
Time to first Occurance of Disease Progression
时间窗: week 52
次要结局
- "Change from Baseline in Liver Fat as Assessed by Mangnetic Resonance imaging - Proton Density Fat Fraction (MRI-PDFF) at Week 52(Change from Baseline in Alanine Aminotransferase (ALT) at Week 52 and Month 36")