Clinical trial NCT03437720: Assessment of the Safety and Effect of SAR425899 Versus Placebo for the Treatment of Non-alcoholic Fatty Liver Disease
Official title: 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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Non-alcoholic Steatohepatitis
Type 2 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2018-02-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria :

* Non-diabetic or type 2 diabetes mellitus with confirmed non-alcoholic steatohepatitis.
* Non-alcoholic fatty liver disease (NAFLD) activity score (NAS) \>=4 with each of its components \>=1.
* Patients without Type 2 diabetes determined by HbA1c (glycated hemoglobin) \<6.5% and Fasting Plasma Glucose (FPG) \<7.0 mmol/L (\<126 mg/dL).
* Stable glycemic control (HbA1c \<9.0%) and metabolic disorders managed with diet/exercise and/or stable dose metformin and/or sulphonylureas for at least 3 months prior to screening (type 2 diabetes patients).
* Signed written informed consent form.

Exclusion criteria:

* Diagnosis of type 1 diabetes mellitus.
* Previous insulin use or use of insulin within the last 6 months, except for episode(s) of short-term treatment (\<15 consecutive days) due to intercurrent illness.
* Body Mass Index (BMI) \<25 kg/m2 or \>45.0 kg/m2.
* Current participation in organized diet/weight reduction program or clinical trial of weight control (within the last 3 months prior to screening), or weight loss attempt, plans for major changes in physical activities or significant change in body weight in the 2 months prior to screening (significant change in body weight is defined as \>=5% self-reported change within 6 months prior to randomization if a pre-existing liver biopsy sample was collected prior to screening period.
* Current treatment with glucose-lowering agent(s) other than metformin or sulphonylureas, weight loss drugs including orlistat, systemic steroids, methotrexate, amiodarone, or Vitamin E.
* Alcoholism (past or present) and/or average alcohol consumption per week \>21 units (210 g) for males, \>14 units (140 g) for females within the last 5 years.
* Poorly controlled hypertension (resting systolic blood pressure (SBP) \>160 mm Hg and/or resting diastolic blood pressure (DBP) \>95 mm Hg) at screening.
* Some liver diseases, pancreatic disease, liver transplantation and types of cancer.
* Pregnant or breast-feeding women.
* Women of childbearing potential (WOCBP) not protected by highly-effective method(s) of birth control and/or who are unwilling or unable to be tested for pregnancy.
* Male subjects, whose partners are able to become pregnant, who do not accept to use a condom during sexual intercourse from study inclusion up to 3 months after last dosing; or who are planning to donate sperm from study inclusion up to 3 months after last dosing.
* Patients with coronary, carotid, or peripheral artery revascularization procedures planned during the screening or treatment phases of the protocol.
* Patients with unstable heart conditions.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Resolution of Non-alcoholic steatohepatitis (NASH)
timeFrame: Week 52
Secondary outcomes:
measure: No hepatocyte ballooning, lobular inflammation score 0 or 1, without worsening of fibrosis
timeFrame: Week 52
measure: Change in overall NAFLD activity score (NAS)
timeFrame: Baseline to week 52
measure: Change in NAS individual components
timeFrame: Baseline to week 52
measure: Change in NAS individual components
timeFrame: Baseline to week 52
measure: Change in NAS individual components
timeFrame: Baseline to week 52
measure: Change in fibrosis score
timeFrame: Baseline to week 52
measure: Major adverse cardiac events
timeFrame: Baseline to week 52
measure: Change in Magnetic Resonance Imaging-determined Proton Density Fat Fraction (MRI-PDFF)
timeFrame: Baseline to week 26 and week 52
measure: Improvement of fibrosis without worsening of hepatocyte ballooning component of NAS
timeFrame: Week 52
measure: Change in body weight
timeFrame: Baseline to week 52
measure: Change in waist circumference
timeFrame: Baseline to week 52
measure: Change in hip circumference
timeFrame: Baseline to week 52
measure: Change in waist to hip ratio
timeFrame: Baseline to week 52
measure: Assessment of pharmacokinetic (PK) parameter: AUC0-24
timeFrame: Week 52
measure: Assessment of PK parameter: Cmax
timeFrame: Week 52
measure: Assessment of PK parameter: Ctrough
timeFrame: Baseline to week 52
Other outcomes:
Locations:
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: