A 36-week, Randomized, Double-blind, Placebo-controlled, Parallel Group Trial to Assess the Efficacy and Safety of PXL065 Versus Placebo in Noncirrhotic Biopsy-proven NonAlcoholic SteatoHepatitis (NASH) Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Poxel SA
- 入组人数
- 117
- 试验地点
- 29
- 主要终点
- Relative Change From Baseline to Week 36 in the Percentage of Liver Fat Content (LFC) (Assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction [MRI-PDFF])
研究概览
简要总结
This study will assess the effect of 3 doses of PXL065 versus placebo on liver fat content in NASH patients after 36 weeks of treatment
详细描述
The study will be performed in patients with NASH. The primary endpoint will be the assessment of the change in the percentage of liver fat content (assessed by MRI-PDFF).
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
- •Patients have given written informed consent
- •Body mass index (BMI) ≤ 50 kg/m²
- •For patients with type 2 diabetes mellitus: either naive of glucose lowering drug or under stable oral glucose lowering drug
- •Estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73m²
- •Liver fat content ≥ 8% on MRI-PDFF
- •Qualifying liver biopsy (NAS) ≥ 4 and fibrosis score F1, F2 or F3
- •Effective contraception for women of child bearing potential
排除标准
- •Evidence of another form of liver disease
- •Evidence of liver cirrhosis
- •Evidence of hepatic impairment
- •Positive serologic evidence of current infectious liver disease
- •History of excessive alcohol intake
- •Acute cardiovascular disease within 6 months prior to Randomization
- •Any disease which in the Investigator's opinion which in the Investigator's opinion would exclude the patient from the study
- •Use of non-permitted concomitant medication
- •Pregnancy or lactation
研究组 & 干预措施
Group 3
PXL065 Dose 3
干预措施: PXL065 (Drug)
Group 1
PXL065 Dose 1
干预措施: PXL065 (Drug)
Group 2
PXL065 Dose 2
干预措施: PXL065 (Drug)
Group 4
Placebo oral tablet
干预措施: Placebo oral tablet (Drug)
结局指标
主要结局
Relative Change From Baseline to Week 36 in the Percentage of Liver Fat Content (LFC) (Assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction [MRI-PDFF])
时间窗: Baseline and Week 36
MRI-PDFF was performed using a standardized imaging protocol, and a central reader analyzed the results. The central reader for this study trained the local imaging centers and provided the imaging manual. Relative change from baseline to Week 36 was calculated as follows: (LFC at Week 36 - LFC at baseline) / LFC at baseline x 100. The primary analysis was performed for the Intent-to-treat Set (ITTS) using an analysis of covariance (ANCOVA) model adjusting for treatment, for stratification factors, and for the baseline LFC as a continuous covariate. LFC missing values at Week 36 were imputed using a multivariate imputation approach by fully conditional specification regression method assuming Missing At Random Mechanism.
Relative Change From Baseline to Week 36 in the Percentage of LFC (Assessed by MRI-PDFF) (Wilcoxon Test Sensitivity Analysis)
时间窗: Baseline and Week 36
MRI-PDFF was performed using a standardized imaging protocol, and a central reader analyzed the results. The central reader for this study trained the local imaging centers and provided the imaging manual. The sensitivity analysis was performed for the Intent-to-treat Set (ITTS) using a non parametric pairwise Wilcoxon test stratified according to T2DM status and NASH CRN fibrosis scoring system. LFC missing values at Week 36 were imputed using a multivariate imputation approach by fully conditional specification regression method assuming Missing At Random Mechanism.
次要结局
- Percentage of Responders (Relative Reduction of at Least 30% in LFC) at Week 36(Baseline and Week 36)
- Change From Baseline to Week 36 in Alanine Amino Transferase (ALT)(Baseline to Week 36)
- Percentage of Responders (Normalization of ALT)(Baseline to Week 36)
- Percentage of Responders (Normalization of AST)(Baseline to Week 36)
- Change From Baseline to Week 36 in Gamma Glutamyltransferase (GGT)(Baseline to Week 36)
- Absolute Change From Baseline to Week 36 in the Percentage of LFC (Assessed by MRI-PDFF)(Baseline and Week 36)
- Change From Baseline to Week 36 in Aspartate Amino Transferase (AST)(Baseline to Week 36)
- Change From Baseline to Week 36 in Alkaline Phosphatase (ALP)(Baseline to Week 36)
- Change From Baseline to Week 36 in Pro-C3(Baseline and Week 36)
- Change From Baseline to Week 36 in Enhanced Liver Fibrosis (ELF) Score(Baseline and Week 36)
- Change From Baseline to Week 36 in Fibrosis-4 (Fib-4) Score(Baseline and Week 36)
- Change From Baseline to Week 36 in NAFLD Fibrosis Score(Baseline and Week 36)
- Change From Baseline to Week 36 in Serum Insulin(Baseline to Week 36)
- Change From Baseline to Week 36 in Serum C-peptide(Baseline to Week 36)
- Improvement of at Least 1 Point in NASH CRN Fibrosis Score From Baseline to Week 36(Baseline and Week 36)
- Improvement in NAS of at Least 2 Points With no Worsening in NASH CRN Fibrosis Score From Baseline to Week 36(Baseline and Week 36)
- NASH Resolution With no Worsening in NASH CRN Fibrosis Score at Week 36(Baseline and Week 36)
- Change From Baseline to Week 36 in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)(Baseline to Week 36)
- Change From Baseline to Week 36 in Adipo-IR(Baseline to Week 36)
- Change From Baseline to Week 36 in Adiponectin(Baseline to Week 36)
- Change From Baseline to Week 36 in Glycated Hemoglobin (HbA1c)(Baseline to Week 36)
- Change From Baseline to Week 36 in Quantitative Insulin Sensitivity Check Index (QUICKI)(Baseline to Week 36)
- Change From Baseline to Week 36 in Weight(Baseline to Week 36)
- NASH Resolution With Improvement of at Least 1 Point in NASH CRN Fibrosis Score at Week 36(Baseline and Week 36)
- Change From Baseline to Week 36 in Fasting Plasma Glucose (FPG)(Baseline to Week 36)