Assessment of the Safety and Effect of SAR425899 Versus Placebo for the Treatment of Non-alcoholic Fatty Liver Disease
- Conditions
- Non-alcoholic SteatohepatitisType 2 Diabetes Mellitus
- Interventions
- Drug: Placebo
- Registration Number
- NCT03437720
- Lead Sponsor
- Sanofi
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SAR425899 (Low Dose) SAR425899 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. Placebo (Low Dose) Placebo 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. Placebo (High Dose) Placebo 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. SAR425899 (High Dose) SAR425899 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.
- Primary Outcome Measures
Name Time Method Resolution of Non-alcoholic steatohepatitis (NASH) 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. -
- Secondary Outcome Measures
Name Time Method Change in Magnetic Resonance Imaging-determined Proton Density Fat Fraction (MRI-PDFF) Baseline to week 26 and week 52 Change from baseline to week 26 and to week 52 in MRI-PDFF-derived total liver fat, liver volume and fractional liver fat content.
Improvement of fibrosis without worsening of hepatocyte ballooning component of NAS Week 52 Percentage of participants with improvement of fibrosis by at least 1 stage without worsening of hepatocyte ballooning component of NAS at week 52
No hepatocyte ballooning, lobular inflammation score 0 or 1, without worsening of fibrosis Week 52 Percentage of participants with absence of hepatocyte ballooning (NAS = 0), lobular inflammation NAS = 0 or 1, without worsening of fibrosis score at week 52.
Change in overall NAFLD activity score (NAS) Baseline to week 52 Change from baseline to week 52 in overall NAFLD activity score (NAS).
Change in NAS individual components Baseline to week 52 Change from baseline to week 52 in individual components of NAS (lobular inflammation).
Change in fibrosis score Baseline to week 52 Change from baseline to week 52 in fibrosis score.
Major adverse cardiac events Baseline to week 52 Number of patients with major cardiac events
Change in body weight Baseline to week 52 Change from baseline to week 52 in body weight
Change in waist circumference Baseline to week 52 Change from baseline to week 52 in waist circumference
Change in waist to hip ratio Baseline to week 52 Change from baseline to week 52 in waist to hip ratio
Change in hip circumference Baseline to week 52 Change from baseline to week 52 in hip circumference
Assessment of pharmacokinetic (PK) parameter: AUC0-24 Week 52 Area under the concentration-time curve from 0 to 24 hours (AUC0-24)
Assessment of PK parameter: Cmax Week 52 Observed maximum plasma concentration after administration (Cmax)
Assessment of PK parameter: Ctrough Baseline to week 52 Plasma concentration immediately prior to treatment administration during repeat dosing levels (Ctrough)