A Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With (NASH) and Fibrosis Stages F2 and F3 ( NATiV3 )
IVA337: A total of 1000 patients will be randomised to receive lanifibranor (800 mg/day) or lanifibranor (1200 mg/day), or matching placebo, employing a 1:1:1 randomisation scheme, respectively, without interruption between Part A and Part B.
Placebo: A total of 1000 patients will be randomised to receive lanifibranor (800 mg/day) or lanifibranor (1200 mg/day), or matching placebo, employing a 1:1:1 randomisation scheme, respectively, without interruption between Part A and Part B.
Study summary
This Phase 3 study is conducted to evaluate lanifibranor in adults with NASH and liver fibrosis histological stage F2 or F3
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Prescreening Criteria:
* Diagnosed with NASH on prior liver biopsy
* Type 2 diabetes with high waist circumference or obesity or hepatic steatosis on ultrasound
* At least 3 of the components of metabolic syndrome
Inclusion Criteria:
1. Male or female, aged ≥18 years at the time of signing informed consent
2. Upon central biopsy reading process: diagnosis of NASH according to the Steatosis-Activity-Fibrosis (SAF):
1. Steatosis score ≥1
2. Activity score: A3 or A4
3. Fibrosis score: F2 or F3
3. No qualitative change in dose for the drugs listed below:
1. Antidiabetic treatment if glucagon-like peptide-1 receptor agonists (GLP1 receptor agonists) or sodium-glucose co-transporter-2 inhibitors (SGLT2 inhibitors): for at least 3 months
2. Vitamin E (if at a dose ≥400 IU/day): for at least 6 months
3. Statins: for at least 3 months
4. No qualitative change in dose for all other chronically administered drugs for at least 3 months prior to Screening
5. Weight stable for 6 months prior to Screening and between the qualifying liver biopsy and Baseline (no more than 5% change for both periods)
6. 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.
Exclusion Criteria:
Liver-related:
1. Documented causes of chronic liver disease other than NASH
2. Histologically documented liver cirrhosis (fibrosis stage F4)
3. History or current diagnosis of hepatocellular carcinoma (HCC)
4. History of or planned liver transplant
5. Positive human immunodeficiency virus (HIV) serology
6. ALT or AST \>5 × ULN
7. AST\<0.6 ULN if the liver biopsy has to be performed in the scope of the study
8. Abnormal synthetic liver function as defined by Screening central laboratory evaluation
9. Haemoglobin \<110 g/L (11 g/dL) for females and \<120 g/L (12 g/dL) for males
10. Patient currently receiving any approved treatment for NASH or obesity
11. Current or recent history (\<5 years) of significant alcohol consumption
12. Treatment with drugs that may cause non-alcoholic fatty liver disease (NAFLD) administered for at least 2 weeks within 12 months prior to qualifying liver biopsy
Glycaemia related:
13. HbA1c \>9% at Screening
14. Diabetes mellitus other than type 2
15. Current treatment with insulin
16. Treatment with PPAR-gamma agonists (thiazolidinediones \[TZDs\]) 12 months before screening or historical biopsy.
Obesity related:
17. Bariatric surgery: Restrictive procedures are allowed, if performed \>6 months prior to the qualifying liver biopsy; malabsorptive procedures and procedures combining both restrictive and malabsorptive methods are not allowed within 5 years of the qualifying liver biopsy.
Cardiovascular related:
18. History of heart failure with reduced left ventricular ejection fraction (LVEF)
19. Atrial fibrillation requiring anticoagulation
20. Unstable heart failure
21. Uncontrolled hypertension at Screening (values \>160/100 mm Hg)
General safety:
22. Women currently breastfeeding
23. Previous exposure to lanifibranor
24. Participation in any clinical trial investigational medicinal product/device within 3 months from Screening or 5 half-lives from Screening, whichever is longer
25. Concomitant treatment with PPAR-alpha agonists (fibrates)
Primary outcome measure(s)
Resolution of NASH and improvement of fibrosis — Part A: Date of randomisation until the date of biopsy at Week 72 Part A: DBPC: Resolution of NASH and improvement of fibrosis at Week 72, defined by NASH CRN scores for ballooning of 0 and inflammation of 0 to 1, and fibrosis score ≥1 stage decrease compared to Baseline
Safety Analyses — 48 weeks after completion of DBPC period Part B: ATE:
* Using the DBPC on-treatment period, comparing the 2 active arms versus placebo
* Using the DBPC +ATE on treatment periods, assessing the 2 active arms. For adverse events, adjudicated liver events, and DILI and MACE events, in addition to the raw cumulative incidence proportions, the exposure-adjusted incidence rates will be provided based on the time patients are at risk.
Trial sites (459)
Facility
City
Region
Status
Objective Health - Birmingham Gastroenterology Associates
Birmingham
Alabama
Digestive Health Specialist of the Southeast
Dothan
Alabama
North Alabama GI Research Center llc
Madison
Alabama
The Institute For Liver Health - Chandler
Chandler
Arizona
Arizona Liver Health - Peoria
Peoria
Arizona
Dignity Health - St. Joseph's Hospital and Medical Center
Phoenix
Arizona
Saint Joseph's Hospital and Medical Center
Phoenix
Arizona
Adobe Gastroenterology
Tucson
Arizona
Arizona Liver Health
Tucson
Arizona
ARcare Center for Clinical Research - Conway
Conway
Arkansas
ARcare Center for Clinical Research
Little Rock
Arkansas
Arkansas Diagnostic Center
Little Rock
Arkansas
Arkansas Gastroenterology
North Little Rock
Arkansas
Summit - Arkansas Gastroenterology
North Little Rock
Arkansas
Fomatmedicalresearch
Camarillo
California
GW Research
Chula Vista
California
Velocity Clinical Research, Chula Vista
Chula Vista
California
TriWest Research Associates
El Cajon
California
Cure Clinical Research, LLC
Fountain Valley
California
SC Clinical Research
Garden Grove
California
Velocity Clinical Research - Gardena
Gardena
California
National Research Institute - Santa Ana
Huntington Park
California
The Clinical Trials Network - Gastro Care Institute
Lancaster
California
National Research Institute - Westlake
Los Angeles
California
National Research Institute - Panorama City
Panorama City
California
California Liver Reearch
Pasadena
California
Cadena Care Institute
Poway
California
Stanford University Medical Center
Redwood City
California
Research and Education, Inc.
San Diego
California
California Pacific Medical Center Research Institute
San Francisco
California
Quest Clinical Research
San Francisco
California
Silicon Valley Research Institute
San Jose
California
Clinical Trial Management Services
Thousand Oaks
California
San Fernando Valley Health Institute
Van Nuys
California
South Denver Gastroenterology - Swedish Medical Center Office
Englewood
Colorado
Yale School of Medicine
New Haven
Connecticut
Synergy Healthcare
Bradenton
Florida
Florida Research Institute
Bradenton
Florida
Tampa Bay Medical Research
Clearwater
Florida
Gastro Florida
Clearwater
Florida
+ 419 more sites — see the full list on the official registry below.
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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