Phase 2b Study in NASH to Assess IVA337 (NATIVE)
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|ClinicalTrials.gov Identifier: NCT03008070|
Recruitment Status : Completed
First Posted : January 2, 2017
Last Update Posted : April 16, 2020
Non-alcoholic steatohepatitis, abbreviated as NASH, is a chronic liver disease that may progress to cirrhosis. The disease is mostly associated with obesity and type 2 diabetes mellitus, or insulin resistance and is very common. However, Treatment of NASH is a significant unmet clinical need.
IVA337 (lanifibranor) is a next generation pan-PPAR (peroxisome proliferator-activated receptors) agonist addressing the pathophysiology of NASH : metabolic, inflammatory and fibrotic.
The purpose of this research is to evaluate the efficacy and the safety of two doses of IVA337 (800mg, 1200 mg) per day for 24 weeks versus placebo in adult NASH patients with liver steatosis and moderate to severe necroinflammation without cirrhosis.
|Condition or disease||Intervention/treatment||Phase|
|Non-Alcoholic Steatohepatitis (NASH)||Drug: IVA337 Drug: Placebo||Phase 2|
Randomized (stratified on diabetes), placebo-controlled, double-blind, parallel-assignment, dose-range multicenter study
There are 3 parallel treatment groups: placebo, IVA337 800mg once a day (Quaque Die, QD) and IVA337 1200mg QD (identical tablets of 400mg IVA337 or placebo). Both, patient and investigator are blinded.
For each patient, the study duration will be an overall of 6 to 8 months (with a 10-day to 4-week selection period, a 24-week treatment period and a 4-week follow-up period).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||247 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized, Double-blind, Placebo-controlled, Multicenter, Dose-range, Proof-of-concept, 24-week Treatment Study of IVA337 in Adult Subjects With Nonalcoholic Steatohepatitis (NASH)|
|Actual Study Start Date :||February 7, 2017|
|Actual Primary Completion Date :||February 20, 2020|
|Actual Study Completion Date :||March 16, 2020|
Experimental: IVA337 1200mg
IVA337 400mg, once a day (Quaque Die, QD) with food
Experimental: IVA337 800mg
IVA337 400mg, once a day (Quaque Die, QD) with food
Placebo Comparator: Placebo
Placebo to match, once a day (Quaque Die, QD) with food
Placebo to match
- Responder analysis based on the improvement of the SAF (steatosis: S, activity : A, and fibrosis: F) activity score. [ Time Frame: 24 weeks ]Responder is defined as a decrease from Baseline of at least 2 points of the SAF activity score combining hepatocellular inflammation and ballooning without worsening of fibrosis
- Percent of patients with resolution of NASH from baseline to end of treatment [ Time Frame: 24 weeks ]
- Percent of patients with a change in components of SAF score from baseline to end of treatment : Steatosis, Lobular inflammation, Ballooning, Fibrosis [ Time Frame: 24 weeks ]
- Change in fibrosis score on a 4-points scale (SAF score) from baseline to end of treatment [ Time Frame: 24 weeks ]
- Change in fibrosis score on modified Ishak score from baseline to end of treatment [ Time Frame: 24 weeks ]
- Liver enzymes change from baseline to end of treatment [ Time Frame: 24 weeks ]Alanine amino transferase (ALT), Aspartate amino transferase (AST), Gamma glutamyl transpeptidase (γGT)
- Inflammatory markers change from baseline to end of treatment [ Time Frame: 24 weeks ]fibrinogen, High-sensitivity C-reactive protein (hs-CRP), alpha2 macroglobulin and haptoglobin
- Glucose metabolism change from baseline to end of treatment [ Time Frame: 24 weeks ](fasting glucose and insulin, Homeostasis model assessment of insulin resistance (HOMA) index and, in subjects with type 2 diabetes mellitus (T2DM), HbA1c
- Main plasma lipids levels change from baseline to end of treatment [ Time Frame: 24 weeks ]Total cholesterol (TC), High-density lipoprotein cholesterol (HDL-C), calculated Low density lipoprotein cholesterol (LDL-C), Triglycerides (TG) and apoA1
- Adiponectin change from baseline to end of treatment [ Time Frame: 24 weeks ]
- Exploratory biomarkers change from baseline to end of treatment [ Time Frame: 24 weeks ]inflammation, lipids, glucides, fibrosis, bone remodeling
- Transient Elastography (TE) and Controlled Attenuation Parameter (CAP) change from baseline to end of treatment [ Time Frame: 24 weeks ]
- If deemed necessary: Immunohistochemistry: change in the semi quantitative score of ballooning and stellate cell activation from baseline to end of treatment [ Time Frame: 24 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03008070
|Principal Investigator:||Sven FRANCQUE, MD, PhD||Division of Gastroenterology and Hepatology, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem, Belgium|