A Phase 2a Study to Assess EYP001a in Patients with NASH
Research type
Research Study
Full title
A Phase 2a, Randomized, Double-Blind, Multicenter, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of EYP001a in Patients With Nonalcoholic Steatohepatitis
IRAS ID
256511
Contact name
Kosh Agrawal
Contact email
Sponsor organisation
ENYO Pharma SA
Eudract number
2018-003119-22
Clinicaltrials.gov Identifier
Duration of Study in the UK
0 years, 7 months, 9 days
Research summary
Research Summary:
Nonalcoholic Steatohepatitis (NASH) is one of the most common chronic liver disorders in western countries. The disease is defined as a liver fat content (LFC) >5%, inflammation and, variably, fibrosis (tissue scarring) at the time of diagnosis. While prognosis is varied, if uncontrolled, NASH will naturally evolve to cirrhosis, liver failure and possibly liver cancer. At this time, treatment options are limited to weight loss and lifestyle changes as there are no approved medicines to treat the disease.EYP001a is a new medicine under development for the treatment of NASH. EYP001a has been designed to activate FXR (Farnesoid X receptor), a key component in bile, lipids and glucose metabolism.
This is a 2-part, randomised, double-blind, placebo-controlled phase 2a study to assess the effects of 2 doses and 2 dosing regimens of EYP001a in NASH patients with Stage 2 and 3 (F2 and F3) fibrosis. The study will evaluate changes in LFC, inflammation and fibrosis, in addition to safety, tolerability, pharmacokinetics (the impact of the body on the medicine) and pharmacodynamics (the impact of the medicine on the body).
The study will be conducted in 2 parts:Part A: Safety Run-in Cohort
Part B: Remaining PatientsParticipants will be randomised in a 1:1:1:1 ratio to one of the four parallel treatment arms for a 12-week treatment period: 1. EYP001a 100mg twice daily, 2. EYP001a 200mg once daily, 3. EYP001a 400mg once daily, 4. Placebo twice daily.
The first 24 participants will be assessed in Part A and undergo a more frequent monitoring schedule and PK Profiling than the remaining participants assigned to Part B. Enrollment in Part B will not start until the safety review committee has evaluated the safety lead-in data and decided it is appropriate to continue enrollment in the study. The UK will participate in Part B of the study only.
Summary of Results:
: Despite the small sample size of Part A (N=24), this study met the primary endpoint with a significant and clinically relevant Liver Fat Content reduction in the pooled vonafexor group compared with the placebo group at Week 12. Body weight was notably reduced from baseline in the vonafexor pooled group compared with placebo and waist circumference was notably reduced from baseline in the pooled vonafexor group. In addition, the pooled vonafexor group showed improved liver biology and the noninvasive imaging fibro-inflammatory biomarker, all related to NASH severity.
The primary endpoint of this study was met in Part B with a significant and clinically relevant Liver Fat Content reduction in both the vonafexor 100 mg administered once daily and vonafexor 200 mg administered once daily groups compared with the placebo group at Week 12. Both doses of vonafexor also improved Liver Fat Content reduction based on thresholds, reduced levels of fibro-inflammatory biomarker, reduced body measurements values, improved liver biology levels, all related to NASH severity.
No unexpected safety concerns were observed with vonafexor in either male or female NASH subjects with Stage F2 to F3 fibrosis in Part A and Part B.REC name
London - West London & GTAC Research Ethics Committee
REC reference
19/LO/0385
Date of REC Opinion
9 Aug 2019
REC opinion
Further Information Favourable Opinion