A randomised, double-blind, placebo-controlled, multicentre, Phase 3 study evaluating long-term efficacy and safety of lanifibranor in adult patients with non-cirrhotic non-alcoholic steatohepatitis (NASH) and fibrosis 2 (F2)/fibrosis 3 (F3) stage of liver fibrosis.
The 3 peroxisome proliferator-activated receptors (PPAR) isoforms play an important role in several components of NASH, from hepatic triglyceride accumulation to fibrosis. Lanifibranor, a pan-PPAR agonist, has demonstrated significant improvement in histological endpoints of NASH in the previous Phase 2b study in patients with highly active NASH. A positive effect of lanifibranor on glucose and lipid metabolism was also demonstrated. This suggests that lanifibranor has the potential to address histological and metabolic aspects of NASH and may be a promising candidate for its treatment.
This Phase 3 study is conducted to evaluate lanifibranor in adults with NASH and liver fibrosis stage 2 or 3.
Who are they looking for?
- Male or female, aged ≥18 years at the time of signing informed consent
- If biopsy performed before Screening, histological diagnosis of NASH with liver fibrosis made no more than 6 months before Screening
- Upon central biopsy reading process: diagnosis of NASH according to the Steatosis-Activity-Fibrosis (SAF):
a Steatosis score ≥1
b Activity score: A3 or A4
Fibrosis score: F2 or F3
MELD score ≤12
- Stable dose for the specified period is required prior to the historical liver biopsy or before Screening visit (whichever is longer) until Baseline visit (Visit 0) for the drugs listed below:
a Antidiabetic treatment if glucagon-like peptide-1 receptor agonists (GLP1 receptor agonists) or sodium-glucose co-transporter-2 inhibitors (SGLT2 inhibitors): Stable dose for at least 3 months
b Vitamin E (if at a dose ≥400 IU/day): Stable dose for at least 6 months
c Statins: Stable dose for at least 3 months
- All chronically administered drugs not covered by criterion #7 (including but not limited to antidiabetic treatments other than GLP1 receptor agonists and SGLT2 inhibitors, antihypertensives, antidepressants, cardiovascular, antihyperlipidemic, etc) must be stable for at least 3 months prior to Screening
- History of at least 1 unsuccessful attempt to reduce body weight by diet and/or exercise within the past 6 years up to 6 months prior to Screening
- Weight stable for 6 months prior to Screening and between the qualifying liver biopsy and Baseline (no more than 5% change for both periods)
- No attempt to change lifestyle (diet and/or exercise) during the 3 months prior to Screening
- Patient agrees to follow recommendations with lifestyle modifications, which will be monitored throughout the whole study period.
- Negative serum pregnancy test at study Screening for females of childbearing potential confirmed by central laboratory. Females of childbearing potential must practice a consistent and proper use of highly effective method of contraception throughout the study and for 1 month after treatment discontinuation. Highly effective contraceptive methods are defined as follows: combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, and sexual abstinence.
For more information, contact Irene at Irena.Petrovski@health.nsw.gov.au