Patients with Non-Alcoholic Steatohepatitis (NASH) MedDRA version: 14.1 Level: PT Classification code 10053219 Term: Non-alcoholic steatohepatitis System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Interventions
Product Name: GFT505 40mg
Product Code: GFT505
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Not applicable
CAS Number: 824932-88-9
Current Sponsor code: GFT505
Concentration unit: mg millig
Sponsors
GENFIT
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provide written informed consent prior to enrolment. 2. Males or females able to read. 3. Females participating in the study must be either of non-child bearing potential (surgically sterilized at least 6 months prior to screening or postmenopausal) or using an efficient double contraception: hormonal contraception (including patch, contraceptive ring, etc.), intra-uterine device or other mechanical contraception method + condom or diaphragm or spermicide for all the duration of the study. For male participants, contraceptive measures must be taken during the study, either by the male participant or his female partner. 4. Aged from 18 to 75 years inclusive at screening. 5. BMI = 45 kg/m². 6. Patients agree to have one liver biopsy during the screening period for diagnostic purpose (if no historical biopsy within 9 months before randomization is available) and one at the end of the treatment period for assessment of the treatment effects. 7. For hypertensive patients, hypertension must be controlled by stable dose of anti-hypertensive medication for at least 2 months prior to screening (and the stable dose can be maintained throughout the study). 8. Patients treated with vitamin E (>400IU/d), or PUFAs (>2g/day) or Ursodeoxycholic acid can be included if drugs are stopped at least 3 months prior to diagnostic liver biopsy and up to the end of the study. 9. Histological confirmation of steatohepatitis on a diagnostic liver biopsy (biopsy obtained within 9 months prior to randomization or during the screening period). Histological diagnostic is confirmed by central reading of the slides (steatosis > 5% + lobular inflammation, any grade + ballooning, any amount). 10. For patients with Type 2 Diabetes, glycemia must be controlled (HbA1c=8.5%). If glycemia is controlled by anti-diabetic drugs, qualitative change (i.e. implementation of a new antidiabetic drug) is not permitted within 6 months prior to randomization and should be avoided during the study. Treatments with metformin, DPPIV inhibitors, GLP1 agonists, sulfamides, insulin are authorised. Sulfamides and insulin are permitted if glycemia is self-monitored by the patient. 11. Patients agree to come to the study visits within the protocol-specified delay. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 270 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 270
Exclusion criteria
Exclusion criteria: 1. Known heart failure (Grade I to IV of NYHA classification). 2. Weight loss of more than 5% within 6 months prior to randomization. 3. History of bariatric surgery. 4. Uncontrolled Blood Pressure (SBP> 160 mmHg and/or DBP>95 mmHg). 5. Type 1 diabetes patients. 6. Patients who had an acute cardiovascular episode within the 6 months prior to screening, or with a history of coronary angioplasty, history of stroke, TIA (Transient Ischemic Attack), Coronary Heart Disease (Angina pectoris, myocardial infarction, revascularisation procedures). 7. Compensated and uncompensated cirrhosis (clinical and/or histological evidence of cirrhosis). Notably, NASH patients with fibrosis stage = 4 according to the NASH CRN fibrosis staging system are excluded. 8. Known alcohol and/or any other drug abuse or dependence in the last five years. Alcohol consumption of more than 2 drink units per day for women and 3 drink units per day for men is considered abusive. One drink unit is defined as 30 mL distilled spirits, 120 mL wine, or 330 mL beer. 9. Patients who have donated blood or blood products within the previous month prior to screening or who plan to donate blood or blood products at any time during the trial and in the 3 months following the end of the study. 10. Pregnant or lactating females. 11. Other well documented causes of chronic liver disease according to standard diagnostic procedures including, but not restricted to: positive HBsAg, positive HCV RNA, suspicion of drug-induced liver disease, autoimmune hepatitis, Wilson's disease, primary biliary cirrhosis, primary sclerosing cholangitis, genetic hemochromatosis documented by homozygosity for the C282Y HFE gene mutation. 12. Patients not covered by Health Insurance System and/or not in compliance with the recommendations of National Law in force. 13. When applicable and according to National Law in force, patient of legal age unable of giving consent or under legal protection or deprived of freedom by judicial or administrative decision. 14. Patients who cannot be contacted in case of emergency. 15. Known intolerance or contra-indication to the list of excipients of GFT505. 16. Patients are currently participating in, plan to participate in, or have participated in an investigational drug or medical device trial within 30 days or five half-lives, whichever is longer, prior to screening. 17. Glitazones (rosiglitazone and pioglitazone) are not permitted 6 months before diagnostic liver biopsy and up to the end of the study. 18. Non-statin lipid-lowering medications such as fibrates are not permitted. Patients that used statins and/or ezetimibe before screening may participate if the dosage has been kept constant for the past 3 months, and is kept constant and stable during the study. 19. Vitamin E (>400IU/day), PUFAs (>2g/day) and Ursodeoxycholic acid should have been stopped 3 months before diagnostic liver biopsy (and can be washed-out during the screening period in case of no available historical biopsy). They are not permitted up to the end of the study. 20. Currently taking drugs that can induce Steatosis/steatohepatitis: corticosteroids (parenteral administration only), amiodarone (Cordarone), Tamoxifen (Nolvadex), methotrexate (Rheumatrex, Trexall). 21. Currently taking any medication that could interfere with study medication absorption, distribution, metabolism or excretion or could lead to induction or inhibition of microsomal enzymes. 22. Evidence of any other
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of GFT505 80mg and GFT505 120mg once daily for 52 weeks versus placebo in reversing histological steatohepatitis without worsening of fibrosis. Worsening of fibrosis is evaluated using NASH CRN fibrosis staging system and defined as: - Progression to stage 3 or 4 for patients at stage 0, 1 or 2 on diagnostic liver biopsy, - Progression to stage 4 for patients at stage 3 on diagnostic liver biopsy.;Secondary Objective: - To evaluate the efficacy of GFT505 80mg and 120mg daily for 52 weeks vs. placebo in reversing histological steatohepatitis. - To assess the improvement on NAS score. - To assess the changes in individual histological scores of steatosis, and hepatic activity. - To evaluate changes in area of fibrosis by morphometry. - To assess changes in fibrosis by the NASH CRN fibrosis staging system. - To assess changes in liver enzymes. - To describe the changes in non-invasive markers of fibrosis and steatosis, in lipid parameters, in insulin resistance, in inflammatory markers, and in safety markers. - To describe the variation in body weight. - To evaluate the changes in cardiovascular risk profile. - To determine PK parameters of GFT505 and GFT1007 after 52 weeks of treatment. - To assess the tolerability and safety of daily administration of GFT505 80mg and 120mg for 52 weeks. - To constitute a Biobank for discovery and validation of biomarkers in NASH/NAFLD and related diseases;Primary end point(s): Percentage of responders defined by the disappearance of steatohepatitis (i.e. patients no longer meeting the criteria for steatohepatitis) without worsening of fibrosis (evaluated using NASH CRN fibrosis staging system).;Timepoint(s) of evaluation of this end point: from Baseline to Week 52. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1- Percentage of responders, defined by the disappearance of steatohepatitis (i.e. patients no longer meeting the criteria for steatohepatitis). 2- Change in NAS score. 3- Changes in stages of steatosis, hepatic activity (lobular inflammation + ballooning). 4- Changes in stages of fibrosis (NASH CRN scoring). 5- Changes in area of fibrosis by morphometry 6- Changes in liver enzymes. 7- Changes in non-invasive markers of fibrosis and steatosis. 8- Changes in lipid parameters. 9- Changes in body weight. 10- Changes in insulin resistance. 11- Changes in inflammatory markers. 12- Changes in safety markers (renal or cardiac function parameters). 13- Changes in cardiovascular risk profile. 14- To determine PK parameters of GFT505 and GFT1007 after 52 weeks of treatment. 15- SAE, AE, physical examination, vital signs, medical history, ECG.;Timepoint(s) of evaluation of this end point: End points n°1 to 13 will be measured from Baseline to week 52. End point n°14 will be measured at 2 time points post dosing at week 52. End point n°15: - collection of AE/SAE throughout the study ; - ECG at baseline, week 26 and week 52 ; - physical examination at each visit ; - vital signs at each visit. | — |
Countries
Belgium, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactProduct Development Department
GENFIT
Outcome results
None listed