CClinicalTrials.gg
Sign In
WithdrawnNCT03437720RestoreUpdated Apr 13, 2022

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

A Phase 2 interventional study of SAR425899 and Placebo in Non-alcoholic Steatohepatitis and Type 2 Diabetes Mellitus, sponsored by Sanofi. Withdrawn. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2022-04-13.

Sponsored by Sanofi · Phase 2, Interventional, and Treatment

Why this study was withdrawn
Sponsor decision to cancel TRIAL, not related to safety concern.
Phase
Phase 2
Study type
Interventional
Enrollment
0
Allocation
Randomized
Ages
18 Years to 80 Years
Sex
All
01

Study 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.
Read the 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.

02

Conditions studied

  • Non-alcoholic Steatohepatitis
  • Type 2 Diabetes Mellitus
03

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.

04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
0 participants (actual)

Study arms

  • 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

  • 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

  • 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

  • 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

Interventions

  • DrugSAR425899

    Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection

  • DrugPlacebo

    Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection

05

What researchers measure

Primary outcomes

  1. Resolution of Non-alcoholic steatohepatitis (NASH)

    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. -

    Time frame: Week 52

Secondary outcomes

  1. No hepatocyte ballooning, lobular inflammation score 0 or 1, without worsening of fibrosis

    Percentage of participants with absence of hepatocyte ballooning (NAS = 0), lobular inflammation NAS = 0 or 1, without worsening of fibrosis score at week 52.

    Time frame: Week 52

  2. Change in overall NAFLD activity score (NAS)

    Change from baseline to week 52 in overall NAFLD activity score (NAS).

    Time frame: Baseline to week 52

  3. Change in NAS individual components

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

    Time frame: Baseline to week 52

  4. Change in NAS individual components

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

    Time frame: Baseline to week 52

  5. Change in NAS individual components

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

    Time frame: Baseline to week 52

  6. Change in fibrosis score

    Change from baseline to week 52 in fibrosis score.

    Time frame: Baseline to week 52

  7. Major adverse cardiac events

    Number of patients with major cardiac events

    Time frame: Baseline to week 52

  8. Change in Magnetic Resonance Imaging-determined Proton Density Fat Fraction (MRI-PDFF)

    Change from baseline to week 26 and to week 52 in MRI-PDFF-derived total liver fat, liver volume and fractional liver fat content.

    Time frame: Baseline to week 26 and week 52

  9. Improvement of fibrosis without worsening of hepatocyte ballooning component of NAS

    Percentage of participants with improvement of fibrosis by at least 1 stage without worsening of hepatocyte ballooning component of NAS at week 52

    Time frame: Week 52

  10. Change in body weight

    Change from baseline to week 52 in body weight

    Time frame: Baseline to week 52

  11. Change in waist circumference

    Change from baseline to week 52 in waist circumference

    Time frame: Baseline to week 52

  12. Change in hip circumference

    Change from baseline to week 52 in hip circumference

    Time frame: Baseline to week 52

  13. Change in waist to hip ratio

    Change from baseline to week 52 in waist to hip ratio

    Time frame: Baseline to week 52

  14. Assessment of pharmacokinetic (PK) parameter: AUC0-24

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

    Time frame: Week 52

  15. Assessment of PK parameter: Cmax

    Observed maximum plasma concentration after administration (Cmax)

    Time frame: Week 52

  16. Assessment of PK parameter: Ctrough

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

    Time frame: Baseline to week 52

06

Study locations

No study locations are listed for this record.

07

References and documents

Individual participant data

Plan to share: Yes — Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03437720
Lead sponsor
Sanofi
Responsible party
Sponsor
First posted
Feb 19, 2018
Start date
May 23, 2019 (estimated)
Primary completion
Aug 25, 2021 (estimated)
Completion
Aug 25, 2021 (estimated)
Last update
Apr 13, 2022

Study contacts

Clinical Sciences & Operations
study director · Sanofi

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is withdrawn, as verified in Apr 2022. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Fatty Liver→

Other studies from this sponsor

Sanofi

Start the discussion