Safety And Efficacy Study Of Orally Administered Epeleuton In Patients With NAFLD

NCT02941549 | Completed Phase 2 Results DMC

• 2 other identifiers: DS102A-022016-000311-33
• Study Type: interventional
• Target: 96
• Locations: 3 countries
• Sites: 16

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)

Conditions

Non Alcoholic Fatty Liver Disease

Outcome Measures

Primary Outcomes (3)

• Change in Serum ALT (Alanine Aminotransferase) From Baseline to Week 16

  Change in serum ALT from baseline to Week 16 using ANCOVA.

  16 Weeks

• Change in Liver Stiffness Measurements by Transient Elastography From Baseline to Week 16

  To evaluate change in liver stiffness measurements using Transient Elastography from baseline to Week 16 using FibroScan® 502 Touch model or equivalent.

  16 Weeks

• Number of Treatment Emergent Adverse Events (TEAEs) in Each Treatment Group Leading to Treatment Discontinuation

  Subjects with at least 1 TEAE leading to treatment discontinuation

  20 Weeks

Secondary Outcomes (9)

• Change in Serum ALT (Alanine Aminotransferase) From Baseline to Weeks 2, 4, 8 and 12

  12 Weeks

• Change in AST (Aspartate Aminotransferase) From Baseline to Weeks 2, 4, 8, 12 and 16

  16 Weeks

• Change in AST:ALT Ratio From Baseline to Weeks 2, 4, 8, 12 and 16

  16 Weeks

• Change in FIB-4 Index From Baseline to Week 16

  16 Weeks

• Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) From Baseline to Week 16

  16 Weeks

Study Arms (3)

Placebo

PLACEBO COMPARATOR

2 x placebo 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks

Other: Placebo capsules

1000 mg Epeleuton

EXPERIMENTAL

1 x Epeleuton 500 mg capsule and 1 x placebo 500 mg capsule orally administered twice a day (4 capsules daily) for 16 weeks

Drug: Epeleuton

2000 mg Epeleuton

EXPERIMENTAL

2 x Epeleuton 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks

Drug: Epeleuton

Interventions

Placebo capsules OTHER

Placebo

Epeleuton DRUG

1000 mg Epeleuton; 2000 mg Epeleuton

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with NAFLD by the presence of hepatic steatosis on imaging or histology in the absence of any secondary causes.
• Patients with an ALT ≥ 1.5 upper limit of normal (ULN) and \< 5 ULN on two occasions 7 or more days apart during screening.
• 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.
• 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.
• Patients whose pre-study clinical laboratory findings do not interfere with their participation in the study, in the opinion of the Investigator.
• Patients aged between 18 and 75 years inclusive.
• 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.
• 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.

You may not qualify if:

• Patients with medical/surgical history of gastric bypass surgery, orthotopic liver transplant (OLT) or listed for OLT.
• Patients with uncontrolled diabetes mellitus type 2, i.e. HbA1c ≥ 9% (75 mmol/mol) at the time of screening.
• 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.
• Patients with inflammatory bowel disease that is either active or requiring medical therapy.
• Patients with diagnosed or suspected autoimmune diseases such as systemic lupus erythematosus and/or rheumatoid arthritis.
• Patients with a history of or active non-liver malignancies other than curatively treated skin cancer (basal cell or squamous cell carcinomas).
• 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.
• 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.
• Patients with known hypersensitivity to any ingredients of the study treatment.
• Patients with a positive test for human immunodeficiency virus antibodies, Hepatitis B surface antigen or Hepatitis C antibodies at screening.
• 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.
• Patients with a significant history of drug/solvent abuse, in the opinion of the investigator.
• 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.
• Patients who have used dietary supplements rich in omega-3 or omega-6 fatty acids in the 4 weeks prior to baseline.
• 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.

Sponsors & Collaborators

• Afimmune: lead

Study Sites (16)

Georgia Site 1

Kutaisi, Georgia

Location

Georgia Site 2

Kutaisi, Georgia

Location

Georgia Site 3

Tbilisi, Georgia

Location

Ukraine Site 3

Dnipro, Ukraine

Location

Ukraine Site 1

Kharkiv, Ukraine

Location

Ukraine Site 2

Kyiv, Ukraine

Location

Ukraine Site 4

Kyiv, Ukraine

Location

UK Site 1

Birmingham, UK, United Kingdom

Location

UK Site 5

Birmingham, UK, United Kingdom

Location

UK Site 6

London, UK, United Kingdom

Location

UK Site 7

Norwich, UK, United Kingdom

Location

UK Site 3

Oxford, UK, United Kingdom

Location

UK Site 4

Plymouth, UK, United Kingdom

Location

UK Site 2

Portsmouth, UK, United Kingdom

Location

UK Site 9

Belfast, United Kingdom

Location

UK Site 8

Liverpool, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 32779505 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

epeleuton

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Afimmune

info@afimmune.com

+3532946380

Study Officials

• Philip Newsome, MBChB, FRCPE, Ph.D

  University of Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2016
• First Posted: October 21, 2016
• Study Start: December 20, 2016
• Primary Completion: January 2, 2019
• Study Completion: March 4, 2019
• Last Updated: October 12, 2022
• Results First Posted: April 21, 2022

Record last verified: 2022-09

Locations

UA (4); GB (9); GE (3)