Clinical study to assess the efficacy and safety of GFT505 once daily in Patients with Non-Alcoholic Steatohepatitis (accumulation of fat in the liver associated with inflammation and liver cell injury at microscopic examination of liver biopsy).
- Conditions
- Patients with Non-Alcoholic Steatohepatitis (NASH)MedDRA version: 16.0Level: PTClassification code 10053219Term: Non-alcoholic steatohepatitisSystem Organ Class: 10019805 - Hepatobiliary disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2012-000295-42-DE
- Lead Sponsor
- GENFIT
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 270
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
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 8 weeks before randomization and up to the end of the study. Non-statin lipid lowering medications can be washed-out during the screening period. Patients that used statins 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 medi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method