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

Study Description

Brief Summary

Detailed Description

Condition or disease	Intervention/treatment	Phase
Non-alcoholic Steatohepatitis Type 2 Diabetes Mellitus	Drug: SAR425899 Other Names Drug: Placebo Other Names	Phase 2

Tracking Information

First Submitted Date	February 13, 2018
Last Update Posted Date	February 13, 2018
Anticipated Start Date	April 30, 2018
Anticipated Completion Date	July 01, 2020
Anticipated Primary Completion Date	July 01, 2020
Results First Submitted Date	N/A
Received Results Disposit Date	N/A

Current Primary Outcome Measures

• 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. -

Original Primary Outcome Measures

Current Secondary Outcome Measures

• 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.

• 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).

• Change in NAS individual components [Time Frame: Baseline to week 52]

  Change from baseline to week 52 in individual components of NAS (steatosis).

• Change in NAS individual components [Time Frame: Baseline to week 52]

  Change from baseline to week 52 in individual components of NAS (hepatocyte ballooning).

• Change in NAS individual components [Time Frame: Baseline to week 52]

  Change from baseline to week 52 in individual components of NAS (lobular inflammation).

• Change in fibrosis score [Time Frame: Baseline to week 52]

  Change from baseline to week 52 in fibrosis score.

• Major adverse cardiac events [Time Frame: Baseline to week 52]

  Number of patients with major cardiac events

• 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.

• 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

• Change in body weight [Time Frame: Baseline to week 52]

  Change from baseline to week 52 in body weight

• Change in waist circumference [Time Frame: Baseline to week 52]

  Change from baseline to week 52 in waist circumference

• Change in hip circumference [Time Frame: Baseline to week 52]

  Change from baseline to week 52 in hip circumference

• Change in waist to hip ratio [Time Frame: Baseline to week 52]

  Change from baseline to week 52 in waist to hip ratio

• Assessment of pharmacokinetic (PK) parameter: AUC0-24 [Time Frame: Week 52]

  Area under the concentration-time curve from 0 to 24 hours (AUC0-24)

• Assessment of PK parameter: Cmax [Time Frame: Week 52]

  Observed maximum plasma concentration after administration (Cmax)

• Assessment of PK parameter: Ctrough [Time Frame: Baseline to week 52]

  Plasma concentration immediately prior to treatment administration during repeat dosing levels (Ctrough)

Original Secondary Outcome Measures

Study Design

Brief Title	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)
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.
Study Type	Interventional
Study Phase	Phase 2
Estimated Enrollment	126
Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	Quadruple
Primary Purpose	Treatment
Conditions	Non-alcoholic Steatohepatitis Type 2 Diabetes Mellitus
Target Follow-Up Duration	N/A
Biospecimen:	N/A
Sampling Method	N/A
Study Population	N/A
Intervention	Drug: SAR425899 Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection Other Names Drug: Placebo Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection Other Names
Study Groups/Cohorts	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. 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. 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. 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.
Study Arms	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. Drug : Placebo 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. Drug : Placebo 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. Drug : SAR425899 Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection 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. Drug : SAR425899 Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection

Arm	Intervention/Treatment
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.	Drug : Placebo 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.	Drug : Placebo 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.	Drug : SAR425899 Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection
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.	Drug : SAR425899 Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection

Recruitment Information

Recruitment Status:	Not yet recruiting
Enrollment	126
Completion Date	July 01, 2020
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.
Gender	All
Age	18 Years to 80 Years
Accepts Healthy Volunteers	No
Contacts	Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 1 then # [email protected]
Listed Location Countries	Not Available

Administrative Information

NCT Number:	NCT03437720
Other Study ID Numbers	ACT15067 2017-002371-26 U1111-1191-5486
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement	Not Available
Responsible Party	,
Study Sponsor	Sanofi
Collaborators	Not Available
Investigators	Study Director Clinical Sciences & Operations Sanofi