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

NCT ID: NCT03437720

Last Updated: 2022-04-13

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-23
• Study Completion Date: 2021-08-25

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.

Conditions

Non-alcoholic Steatohepatitis; Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

SAR425899

Intervention Type: DRUG

Pharmaceutical form: Solution for injection

Route of administration: Subcutaneous injection

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.

Group Type: EXPERIMENTAL

SAR425899

Intervention Type: DRUG

Pharmaceutical form: Solution for injection

Route of administration: Subcutaneous injection

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Pharmaceutical form: Solution for injection

Route of administration: Subcutaneous injection

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Pharmaceutical form: Solution for injection

Route of administration: Subcutaneous injection

Interventions

SAR425899

Pharmaceutical form: Solution for injection

Route of administration: Subcutaneous injection

Intervention Type: DRUG

Placebo

Pharmaceutical form: Solution for injection

Route of administration: Subcutaneous injection

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Other Identifiers

2017-002371-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1191-5486

Identifier Type: OTHER

Identifier Source: secondary_id

ACT15067

Identifier Type: -

Identifier Source: org_study_id