Clinical Trials/NCT02941549

NCT02941549

Completed

Phase 2

A Randomised, Double-Blind, Placebo-Controlled, Exploratory Phase IIa Study To Assess The Safety And Efficacy Of Orally Administered Epeleuton In NAFLD Patients.

Afimmune16 sites in 3 countries96 target enrollmentDecember 20, 2016

ConditionsNon Alcoholic Fatty Liver Disease

InterventionsPlacebo capsules Epeleuton

DrugsEpeleuton

Overview

Phase: Phase 2
Intervention: Placebo capsules
Conditions: Non Alcoholic Fatty Liver Disease
Sponsor: Afimmune
Enrollment: 96
Locations: 16
Primary Endpoint: Change in Serum ALT (Alanine Aminotransferase) From Baseline to Week 16
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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)

Registry

clinicaltrials.gov

Start Date

December 20, 2016

End Date

March 4, 2019

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Afimmune

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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.

Exclusion Criteria

•Patients with an unstable metabolic condition such as weight change \> 5% in the 3 months prior to inclusion.
•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.

Arms & Interventions

Placebo

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

Intervention: Placebo capsules

1000 mg Epeleuton

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

Intervention: Epeleuton

2000 mg Epeleuton

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

Intervention: Epeleuton

Outcomes

Primary Outcomes

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

Time Frame: 16 Weeks

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

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

Time Frame: 16 Weeks

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

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

Time Frame: 20 Weeks

Subjects with at least 1 TEAE leading to treatment discontinuation

Secondary Outcomes

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)
Change in ELF (Enhanced Liver Fibrosis Score) From Baseline to Week 16(16 Weeks)
Change in HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) From Baseline to Weeks 2, 4, 8, 12 and 16(16 Weeks)
Change in Adipo-IR (Adipose Tissue Insulin Resistance) From Baseline to Weeks 2, 4, 8, 12 and 16.(16 Weeks)
Change in Hepatic Fat Measured by CAP (Controlled Attenuation Parameter) From Baseline to Week 16.(16 Weeks)