Clinical trial NCT02941549: Safety And Efficacy Study Of Orally Administered Epeleuton In Patients With NAFLD
Official title: A Randomised, Double-Blind, Placebo-Controlled, Exploratory Phase IIa Study To Assess The Safety And Efficacy Of Orally Administered Epeleuton In NAFLD Patients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non Alcoholic Fatty Liver Disease
Lead sponsor: Afimmune
Sponsor class: INDUSTRY
First posted: 2016-10-21
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Change in Serum ALT (Alanine Aminotransferase) From Baseline to Week 16
timeFrame: 16 Weeks
measure: Change in Liver Stiffness Measurements by Transient Elastography From Baseline to Week 16
timeFrame: 16 Weeks
measure: Number of Treatment Emergent Adverse Events (TEAEs) in Each Treatment Group Leading to Treatment Discontinuation
timeFrame: 20 Weeks
Secondary outcomes:
measure: Change in Serum ALT (Alanine Aminotransferase) From Baseline to Weeks 2, 4, 8 and 12
timeFrame: 12 Weeks
measure: Change in AST (Aspartate Aminotransferase) From Baseline to Weeks 2, 4, 8, 12 and 16
timeFrame: 16 Weeks
measure: Change in AST:ALT Ratio From Baseline to Weeks 2, 4, 8, 12 and 16
timeFrame: 16 Weeks
measure: Change in FIB-4 Index From Baseline to Week 16
timeFrame: 16 Weeks
measure: Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) From Baseline to Week 16
timeFrame: 16 Weeks
measure: Change in ELF (Enhanced Liver Fibrosis Score) From Baseline to Week 16
timeFrame: 16 Weeks
measure: Change in HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) From Baseline to Weeks 2, 4, 8, 12 and 16
timeFrame: 16 Weeks
measure: Change in Adipo-IR (Adipose Tissue Insulin Resistance) From Baseline to Weeks 2, 4, 8, 12 and 16.
timeFrame: 16 Weeks
measure: Change in Hepatic Fat Measured by CAP (Controlled Attenuation Parameter) From Baseline to Week 16.
timeFrame: 16 Weeks
Other outcomes:
Locations:
city: Kutaisi
country: Georgia
facility: Georgia Site 1
city: Kutaisi
country: Georgia
facility: Georgia Site 2
city: Tbilisi
country: Georgia
facility: Georgia Site 3
city: Dnipro
country: Ukraine
facility: Ukraine Site 3
city: Kharkiv
country: Ukraine
facility: Ukraine Site 1
city: Kyiv
country: Ukraine
facility: Ukraine Site 2
city: Kyiv
country: Ukraine
facility: Ukraine Site 4
city: Birmingham
country: United Kingdom
facility: UK Site 1
state: UK
city: Birmingham
country: United Kingdom
facility: UK Site 5
state: UK
city: London
country: United Kingdom
facility: UK Site 6
state: UK
city: Norwich
country: United Kingdom
facility: UK Site 7
state: UK
city: Oxford
country: United Kingdom
facility: UK Site 3
state: UK
city: Plymouth
country: United Kingdom
facility: UK Site 4
state: UK
city: Portsmouth
country: United Kingdom
facility: UK Site 2
state: UK
city: Belfast
country: United Kingdom
facility: UK Site 9
city: Liverpool
country: United Kingdom
facility: UK Site 8
Study officials:
affiliation: University of Birmingham
name: Philip Newsome, MBChB, FRCPE, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Climax J, Newsome PN, Hamza M, Weissbach M, Coughlan D, Sattar N, McGuire DK, Bhatt DL. Effects of Epeleuton, a Novel Synthetic Second-Generation n-3 Fatty Acid, on Non-Alcoholic Fatty Liver Disease, Triglycerides, Glycemic Control, and Cardiometabolic and Inflammatory Markers. J Am Heart Assoc. 2020 Aug 18;9(16):e016334. doi: 10.1161/JAHA.119.016334. Epub 2020 Aug 11.