A Phase 3, Multinational, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy, Safety, and Clinical Outcomes of Pemvidutide in Subjects With Noncirrhotic Metabolic Dysfunction-Associated Steatohepatitis (MASH)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,800
- 试验地点
- 9
- 主要终点
- Clinical Outcome Event
研究概览
简要总结
Phase 3, multicenter, multinational, 2-cohort, randomized, double-blind, placebo controlled, parallel-group pivotal study to evaluate the efficacy, safety, and clinical outcomes of pemvidutide treatment in subjects with noncirrhotic (F2 or F3) metabolic dysfunction-associated steatohepatitis (MASH). Participants will be assigned either to Cohort 1 based on screening histologic (liver biopsy) criteria or to Cohort 2 based on non-invasive test criteria.
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
- •All subjects:
- •No significant changes in body weight (±5%) and not participating in a structured weight loss program for the 3 months prior to screening (or since the historical biopsy, if applicable)
- •Body mass index (BMI) ≥ 25.0 kg/m2; if Asian, BMI ≥ 23.0 kg/m2
- •Type 2 diabetes (T2D) or at least 2 components of metabolic syndrome
- •Subject agrees to have liver biopsy(ies) as required per protocol
- •Cohort 1 - Histologic diagnosis of F2/F3 MASH based on liver biopsy during screening or historical biopsy within 6 months before screening
- •Cohort 2 - Presumed F2/F3 MASH based on noninvasive testing
排除标准
- •Cirrhosis (F4); portal hypertension or hepatic decompensation; acute or chronic liver disease other than MASH; liver function tests (ALT, AST; alkaline phosphatase; total bilirubin; INR; and platelet count) outside of acceptable ranges; positive HBsAg; active hepatitis C
- •Uncontrolled T2D or clinically significant persistent hyperglycemia
研究组 & 干预措施
Placebo
干预措施: Placebo (Other)
Pemvidutide 1.8 mg
干预措施: Pemvidutide (Drug)
Pemvidutide 2.4 mg
干预措施: Pemvidutide (Drug)
结局指标
主要结局
Clinical Outcome Event
时间窗: Baseline through end of study (approximately Month 60)
Time to first occurrence of any of the following events through the end of the study: Histologic progression to cirrhosis (F4) on liver biopsy; Liver related events; Liver transplantation; or Death due to any cause
Histological Response: MASH resolution
时间窗: Baseline through Week 52
Proportion of subjects achieving MASH resolution (according to NASH Clinical Research Network \[CRN\] classification) without worsening of fibrosis
Histological Response: Fibrosis improvement
时间窗: Baseline through Week 52
Proportion of subjects achieving ≥ 1 stage improvement in liver fibrosis according to the NASH CRN fibrosis staging system without worsening of MASH
次要结局
- Histologic Response: Proportion of subjects achieving both MASH resolution (according to NASH CRN classification) without worsening of fibrosis and ≥ 1 stage improvement in liver fibrosis without worsening of MASH(Baseline through Week 52)
- HistoIndex qFibrosis: Proportion of subjects with at least a 1 stage improvement in qFibrosis(Baseline through Week 52)
- Anthropometric parameters: Relative (%) change from baseline in body weight (kg)(Baseline through End of Study (approximately Month 60))
- Anthropometric parameters: Relative (%) change from baseline in body mass index (BMI; kg/m2)(Baseline through End of Study (approximately Month 60))
- Anthropometric parameters: Relative (%) change from baseline in waist circumference (cm)(Baseline through End of Study (approximately Month 60))
- Noninvasive Tests of MASH Inflammatory and Fibrotic Activity: Absolute change from baseline in alanine aminotransferase (ALT; U/L)(Baseline through End of Study (approximately Month 60))
- Noninvasive Tests of MASH Inflammatory and Fibrotic Activity: Absolute change from baseline in enhanced liver fibrosis (ELF) score(Baseline through End of Study (approximately Month 60))
- Noninvasive Tests of MASH Inflammatory and Fibrotic Activity: Relative (%) change from baseline in vibration controlled transient elastography (VCTE; kPa) by Fibroscan(Baseline through End of Study (approximately Month 60))
- HRQoL: Change from baseline in core symptoms of MASH on the NASH-CHECK questionnaire.(Baseline through End of Study (approximately Month 60))
- HRQoL: Change from baseline in Short-form 36 (SF-36) summary scores.(Baseline through End of Study (approximately Month 60))
- HRQoL: Change from baseline in Chronic Liver Disease Questionnaire for Nonalcoholic Steatohepatitis (CLDQ-NASH) domain scores.(Baseline through End of Study (approximately Month 60))