Assessment of the Safety and Effect of SAR425899 Versus Placebo for the Treatment of Non-alcoholic Fatty Liver Disease (Restore)

Sanofi

Status and phase: Withdrawn; Phase 2

Conditions: Type 2 Diabetes Mellitus; Non-alcoholic Steatohepatitis

Treatments: Drug: SAR425899; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03437720

2017-002371-26 (EudraCT Number)

U1111-1191-5486 (Other Identifier)

ACT15067

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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0 participants in 4 patient groups, including a placebo group

SAR425899 (Low Dose)

Experimental group

Description:

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.

Treatment:

Drug: SAR425899

SAR425899 (High Dose)

Experimental group

Description:

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.

Treatment:

Drug: SAR425899

Placebo (Low Dose)

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Placebo (High Dose)

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo