Safety And Efficacy Study Of Orally Administered Epeleuton In Patients With NAFLD
Condition: Non Alcoholic Fatty Liver Disease
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Intervention: Placebo capsules; Epeleuton
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 96.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The purpose of this randomised, double-blind, placebo-controlled, parallel group study is to
      assess the safety and efficacy of orally administered Epeleuton capsules versus placebo in
      the treatment of adult patients with Non Alcoholic Fatty Liver Disease (NAFLD)
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients diagnosed with NAFLD by the presence of hepatic steatosis on imaging or
             histology in the absence of any secondary causes.

          2. Patients with an ALT ≥ 1.5 upper limit of normal (ULN) and < 5 ULN on two occasions 7
             or more days apart during screening.

          3. Patients with historical liver biopsy showing NASH and/or ≥ F1 fibrosis OR NFS ≥
             -1.455 OR Fib- 4 ≥ 1.3 OR Fibroscan ≥8kPa within 3 months of screening.

          4. Patients with a body mass index (BMI) between 25.0 and 40.0 kg/m² inclusive. Patients
             with a history of controlled obesity or controlled diabetes are allowed on the study.

          5. Patients whose pre-study clinical laboratory findings do not interfere with their
             participation in the study, in the opinion of the Investigator.

          6. Patients aged between 18 and 75 years inclusive.

          7. Female patients and male patients with female partners of child bearing potential must
             use adequate contraception or have a sterilized partner for the duration of the study.
             Adequate contraception is defined as: systemic hormonal contraceptives; intrauterine
             device or barrier method of contraception in conjunction with spermicide; or agree to
             sexual abstinence, defined as a patient refraining from heterosexual intercourse
             during the entire period of risk associated with the study treatments and in line with
             their preferred and usual lifestyle. Hormonal contraceptives must be on a stable dose
             for at least one month before baseline.

          8. Patients who are able to communicate well with the Investigator, to understand and
             comply with the requirements of the study, and understand and sign the written
             informed consent.

        Exclusion Criteria:

          1. Patients with an unstable metabolic condition such as weight change > 5% in the 3
             months prior to inclusion.

          2. Patients with medical/surgical history of gastric bypass surgery, orthotopic liver
             transplant (OLT) or listed for OLT.

          3. Patients with uncontrolled diabetes mellitus type 2, i.e. HbA1c ≥ 9% (75 mmol/mol) at
             the time of screening.

          4. Patients with decompensated or severe liver disease as evidenced by one or more of the
             following: confirmed cirrhosis or suspicion of cirrhosis, esophageal varices, ascites,
             suspicion of portal hypertension, hospitalization for liver disease within 60 days of
             screening, bilirubin ≥ 2 x ULN, or ALT or AST ≥ 5 x ULN. Patients with Gilbert's
             syndrome are eligible if the conjugated bilirubin is ≤ 1.5 x ULN.

          5. Patients with inflammatory bowel disease that is either active or requiring medical
             therapy.

          6. Patients with diagnosed or suspected autoimmune diseases such as systemic lupus
             erythematosus and/or rheumatoid arthritis.

          7. Patients with a history of or active non-liver malignancies other than curatively
             treated skin cancer (basal cell or squamous cell carcinomas).

          8. Patients with a significant systemic or major illness other than liver disease,
             including coronary artery disease, cerebrovascular disease, pulmonary disease, renal
             insufficiency, serious psychiatric disease, respiratory or hypertensive disease, as
             well as diabetes and arthritis that, in the opinion of the Investigator, would
             preclude the patient from participating in and completing the study.

          9. Patients requiring anti-diabetic treatment (including insulin sensitizing agents),
             and/or lipid lowering treatment, and who are not on a stable dose for at least 3
             months prior to screening should be excluded. If patients are insulin dependent this
             treatment should have commenced at least 3 months prior to screening, however changes
             in dose are permitted.

         10. Patients with known hypersensitivity to any ingredients of the study treatment.

         11. Patients with a positive test for human immunodeficiency virus antibodies, Hepatitis B
             surface antigen or Hepatitis C antibodies at screening.

         12. Patients with liver disease of other etiologies such as drug-induced, autoimmune
             hepatitis, primary biliary cholangitis, primary sclerosing cholangitis,
             haemochromatosis, alpha-1 antitrypsin deficiency or Wilson's disease.

         13. Patients with a significant history of drug/solvent abuse, in the opinion of the
             investigator.

         14. Patients with a history of alcohol abuse in the opinion of the Investigator, or who
             currently drinks in excess of 21 units per week (males) or 14 units per week
             (females), whereby a unit consists of 10ml or 8mg of pure alcohol.

         15. Patients who have used dietary supplements rich in omega-3 or omega-6 fatty acids in
             the 4 weeks prior to baseline.

         16. Patients who have participated in any other clinical study with an investigational
             drug within 3 months before the first day of administration of study treatment.

         17. Patients who are pregnant, planning pregnancy, breastfeeding and/or are unwilling to
             use adequate contraception (as specified in inclusion criterion 7) during the study.

         18. Patients, in the opinion of the Investigator, not suitable to participate in the
             study.