- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03437720
Assessment of the Safety and Effect of SAR425899 Versus Placebo for the Treatment of Non-alcoholic Fatty Liver Disease (Restore)
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)
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.
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection |
Experimental: 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.
|
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection |
Placebo Comparator: 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.
|
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection |
Placebo Comparator: 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.
|
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Resolution of Non-alcoholic steatohepatitis (NASH)
Time Frame: 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.
-
|
Week 52
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
No hepatocyte ballooning, lobular inflammation score 0 or 1, without worsening of fibrosis
Time Frame: 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.
|
Week 52
|
Change in overall NAFLD activity score (NAS)
Time Frame: Baseline to week 52
|
Change from baseline to week 52 in overall NAFLD activity score (NAS).
|
Baseline to week 52
|
Change in NAS individual components
Time Frame: Baseline to week 52
|
Change from baseline to week 52 in individual components of NAS (steatosis).
|
Baseline to week 52
|
Change in NAS individual components
Time Frame: Baseline to week 52
|
Change from baseline to week 52 in individual components of NAS (hepatocyte ballooning).
|
Baseline to week 52
|
Change in NAS individual components
Time Frame: Baseline to week 52
|
Change from baseline to week 52 in individual components of NAS (lobular inflammation).
|
Baseline to week 52
|
Change in fibrosis score
Time Frame: Baseline to week 52
|
Change from baseline to week 52 in fibrosis score.
|
Baseline to week 52
|
Major adverse cardiac events
Time Frame: Baseline to week 52
|
Number of patients with major cardiac events
|
Baseline to week 52
|
Change in Magnetic Resonance Imaging-determined Proton Density Fat Fraction (MRI-PDFF)
Time Frame: 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.
|
Baseline to week 26 and week 52
|
Improvement of fibrosis without worsening of hepatocyte ballooning component of NAS
Time Frame: 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
|
Week 52
|
Change in body weight
Time Frame: Baseline to week 52
|
Change from baseline to week 52 in body weight
|
Baseline to week 52
|
Change in waist circumference
Time Frame: Baseline to week 52
|
Change from baseline to week 52 in waist circumference
|
Baseline to week 52
|
Change in hip circumference
Time Frame: Baseline to week 52
|
Change from baseline to week 52 in hip circumference
|
Baseline to week 52
|
Change in waist to hip ratio
Time Frame: Baseline to week 52
|
Change from baseline to week 52 in waist to hip ratio
|
Baseline to week 52
|
Assessment of pharmacokinetic (PK) parameter: AUC0-24
Time Frame: Week 52
|
Area under the concentration-time curve from 0 to 24 hours (AUC0-24)
|
Week 52
|
Assessment of PK parameter: Cmax
Time Frame: Week 52
|
Observed maximum plasma concentration after administration (Cmax)
|
Week 52
|
Assessment of PK parameter: Ctrough
Time Frame: Baseline to week 52
|
Plasma concentration immediately prior to treatment administration during repeat dosing levels (Ctrough)
|
Baseline to week 52
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ACT15067
- 2017-002371-26 (EudraCT Number)
- U1111-1191-5486 (Other Identifier: UTN)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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