A 52-week Double-blind, Randomized, Placebo-controlled, Phase 2 Study to Assess the Efficacy and Safety of SAR425899 for the Treatment of Non-alcoholic Steatohepatitis (NASH)
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- Sanofi
- 主要终点
- Resolution of Non-alcoholic steatohepatitis (NASH)
研究概览
简要总结
Primary Objective:
- To evaluate the dose response relationship of SAR425899 compared to placebo on resolution of non-alcoholic steatohepatitis (NASH) with no worsening of fibrosis in diabetic and non-diabetic patients with histopathologically-confirmed NASH.
Secondary Objectives:
- To assess the effect of SAR425899 on overall non-alcoholic fatty liver disease (NAFLD) activity score (NAS), individual components of NAS (steatosis, hepatocyte ballooning, and lobular inflammation), and fibrosis score.
- To assess to the effect of SAR425899 on MRI-PDFF (Magnetic Resonance Imaging-determined Proton Density Fat Fraction) derived parameters (total liver fat, liver volume, and fractional liver fat content).
- To assess the effect of SAR425889 on body weight and waist/hip circumference ratio.
- To assess SAR425899 pharmacokinetics.
- To assess safety and tolerability of SAR425899.
详细描述
Study duration per participant will be approximately 64 weeks, consisting of up to 8 weeks screening plus 52 weeks treatment and 4 weeks post treatment follow-up.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
SAR425899 (Low Dose)
Once daily dose with weekly dose escalations, if tolerated, until target dose is reached. From week 14 (Day 99) until week 52, no further dose adjustments are planned.
干预措施: SAR425899 (Drug)
SAR425899 (High Dose)
Once daily dose with weekly dose escalations, if tolerated, until target dose is reached. From week 14 (Day 99) until week 52, no further dose adjustments are planned.
干预措施: SAR425899 (Drug)
Placebo (Low Dose)
Once daily dose with weekly dose escalations, if tolerated, until target dose is reached. From week 14 (Day 99) until week 52, no further dose adjustments are planned.
干预措施: Placebo (Drug)
Placebo (High Dose)
Once daily dose with weekly dose escalations, if tolerated, until target dose is reached. From week 14 (Day 99) until week 52, no further dose adjustments are planned.
干预措施: Placebo (Drug)
结局指标
主要结局
Resolution of Non-alcoholic steatohepatitis (NASH)
时间窗: Week 52
Percentage of participants with absence of hepatocyte ballooning (NAFLD - non-alcoholic fatty liver disease - activity score, NAS = 0) without worsening of fibrosis score at week 52. -
次要结局
- Change in Magnetic Resonance Imaging-determined Proton Density Fat Fraction (MRI-PDFF)(Baseline to week 26 and week 52)
- Improvement of fibrosis without worsening of hepatocyte ballooning component of NAS(Week 52)
- No hepatocyte ballooning, lobular inflammation score 0 or 1, without worsening of fibrosis(Week 52)
- Change in overall NAFLD activity score (NAS)(Baseline to week 52)
- Change in NAS individual components(Baseline to week 52)
- Change in fibrosis score(Baseline to week 52)
- Major adverse cardiac events(Baseline to week 52)
- Change in body weight(Baseline to week 52)
- Change in waist circumference(Baseline to week 52)
- Change in waist to hip ratio(Baseline to week 52)
- Change in hip circumference(Baseline to week 52)
- Assessment of pharmacokinetic (PK) parameter: AUC0-24(Week 52)
- Assessment of PK parameter: Cmax(Week 52)
- Assessment of PK parameter: Ctrough(Baseline to week 52)