A Phase 2b Study of Icosabutate in Fatty Liver Disease
- Conditions
- Non Alcoholic Steatohepatitis (NASH)
- Interventions
- Drug: Placebo
- Registration Number
- NCT04052516
- Lead Sponsor
- NorthSea Therapeutics B.V.
- Brief Summary
A Phase 2b study to evaluate the efficacy of different doses of NST-4016 on the resolution of NASH without worsening of fibrosis
- Detailed Description
This is a 62 week (including screening and follow-up), multicenter, randomized, double blind, placebo-controlled, parallel group study in male and female patients with a histological diagnosis of NASH. The study includes a screening period, double blind treatment period, and post-treatment follow up
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 280
- Provides signed written informed consent and agrees to comply with the study protocol.
- Is a male or female aged 18 to 75 years, inclusive.
- Has a histological diagnosis of NASH prior to study entry
- Has (NAS) greater than or equal to 4, with a score of at least 1 in each component (steatosis, lobular inflammation, and ballooning),
- Has a fibrosis score F1 to F3, inclusive (F1 capped at 30%),
- Has a Proton Density Fat Fraction (PDFF) greater than or equal to 10% on MRI at screening
- Has a known history of alcohol abuse or daily heavy alcohol consumption
- Has had bariatric surgery within the past 5 years
- Has significant systemic or major illnesses other than liver disease
- Has a recent (within 6 months) history of cardiac dysrhythmias and/or cardiovascular disease
- Has uncontrolled arterial hypertension
- Positive for Hep B, Hepatitis C Virus (HCV) or HCV Polymerase Chain Reaction (PCR)
- Has type 1 diabetes mellitus
- Has diabetic ketoacidosis
- Has a history of liver decompensation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo oral capsules taken one daily for 52 weeks Icosabutate 300mg Icosabutate Icosabutate 300mg oral capsule taken once daily for 52 weeks Icosabutate 600mg Icosabutate Icosabutate 600mg oral capsules taken once daily for 52 weeks
- Primary Outcome Measures
Name Time Method Percentage of Patients With Resolution of NASH, Defined as Disappearance of Ballooning (Score = 0) With Lobular Inflammation Score 0 or 1, With no Worsening of Fibrosis. 52 weeks
- Secondary Outcome Measures
Name Time Method Percentage of Patients With Fibrosis Improvement, Defined as Greater Than or Equal to 1 Stage of Fibrosis Improvement and no Worsening of Steatohepatitis (Inflammation/Ballooning). 52 weeks Percentage of Patients With Fibrosis Improvement, Defined as Greater Than or Equal to 1 Stage of Fibrosis Improvement. 52 weeks Changes in the Liver Enzymes Aspartate Aminotransferase (AST)U/L, Alanine Aminotransferase ( ALT)U/L and Gamma Glutamyl Transferase (GGT) U/L From Baseline 52 weeks Change in Bilirubin Micromol/L From Baseline 52 weeks Change From Baseline in Inflammation Marker hsCRP 52 weeks Change From Baseline in Fibrosis Activity Marker Pro-C3 52 weeks Change From Baseline in Fibrosis Activity Marker Enhanced Liver Fibrosis (ELF) Test 52 weeks ELF is a blood test that measures liver fibrosis by analyzing three markers in the blood: Hyaluronic acid (HA), Procollagen III amino-terminal peptide (PIIINP), and Tissue inhibitor of matrix metalloproteinase 1 (TIMP-1). The higher the score the higher the levels of markers in the blood. ELF score = 2.278 + 0.851 × ln(HA) + 0.751 × ln(PIIINP) + 0.394 × ln(TIMP-1). As the score is a composite measure of the levels of three markers in the blood, there is not a finite range for this parameter.
Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) 52 weeks HOMA-IR is a measure of insulin resistance and metabolic status. The higher the score, the higher the level of insulin resistance. HOMA-IR = fasting glucose \[mmol/L)\] × fasting insulin \[mIU/L\]/22.5. As HOMA-IR is a composite score using 2 parameters, it does not have a finite range.
Change From Baseline in Composite Disease Activity Score (Composite NASH Score of Inflammation, Ballooning, Fibrosis) 52 weeks The disease activity score can range from 0 to 8 and is calculated by the sum of scores of steatosis (0-3), lobular inflammation (0-3) and hepatocyte ballooning (0-2). The higher the score the more severe the disease.
Change From Baseline in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) 52 weeks A histological scoring system that assesses a liver biopsy and gives scores for steatosis (0-3), lobular inflammation (0-3), and hepatocyte ballooning (0-2) giving a total score of (0-8). The higher the score the more severe the disease
Changes in Individual Histological Scores for Steatosis, Ballooning, Inflammation, and Fibrosis From Baseline 52 weeks Changes in scores for the individual component parts of the Nonalcoholic fatty liver disease (NAFLD) activity score (NAS) as judged by a pathologist examining sections from a liver biopsy; steatosis (range 0-3), lobular inflammation (range 0-3), and hepatocyte ballooning (range 0-2) In all cases a higher number denotes more severe disease activity
Change From Baseline in Magnetic Resonance Imaging-Proton Density-Fat Fraction (MRI-PDFF) 52 weeks MRI-PDFF is a quantitative imaging biomarker that measures the fat fraction of tissue by correcting factors influencing magnetic resonance signal intensity.
Trial Locations
- Locations (36)
Covenant Research LLC
🇺🇸Sarasota, Florida, United States
Gastrointestinal Specialists of Georgia PC
🇺🇸Marietta, Georgia, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Aventiv Research, Inc.
🇺🇸Columbus, Ohio, United States
National Research Institute - Wilshire
🇺🇸Los Angeles, California, United States
Arizona Liver Health
🇺🇸Tucson, Arizona, United States
South Denver Gastroenterology
🇺🇸Englewood, Colorado, United States
Texas Digestive Disease Consultants
🇺🇸Dallas, Texas, United States
Fundacion de Investigacion (FDI)
🇵🇷San Juan, Puerto Rico
Arizona Liver Health - Glendale
🇺🇸Glendale, Arizona, United States
Alliance Clinical Research
🇺🇸Poway, California, United States
National Research Institute - Panorama
🇺🇸Panorama City, California, United States
Southern Therapy and Advanced Research LLC
🇺🇸Jackson, Mississippi, United States
Adobe Clinical Research, LLC
🇺🇸Tucson, Arizona, United States
Cumberland Research Associates, LLC
🇺🇸Fayetteville, North Carolina, United States
Liver Associates of Texas
🇺🇸Houston, Texas, United States
Pinnacle Clinical Research
🇺🇸San Antonio, Texas, United States
Quality Research Inc
🇺🇸San Antonio, Texas, United States
American Research Corporation
🇺🇸San Antonio, Texas, United States
Brooke Army Medical Center
🇺🇸San Antonio, Texas, United States
Texas Digestive Disease Consultants - Webster
🇺🇸Webster, Texas, United States
Arkansas Gastroenterology - North Little Rock
🇺🇸North Little Rock, Arkansas, United States
Fresno Clinical Research Center
🇺🇸Fresno, California, United States
Central ResearchAssociates Inc.
🇺🇸Birmingham, Alabama, United States
National Research Institute - Huntington Park
🇺🇸Huntington Park, California, United States
Sensible Healthcare LLC
🇺🇸Ocoee, Florida, United States
Gastrointestinal Associates, PA
🇺🇸Flowood, Mississippi, United States
Kansas City Research Institute
🇺🇸Kansas City, Missouri, United States
Gastro One
🇺🇸Germantown, Tennessee, United States
Premier Research
🇺🇸Clarksville, Tennessee, United States
Hunter Holmes McGuire VA Medical Center
🇺🇸Richmond, Virginia, United States
Excel Medical Clinical Trials, LLC
🇺🇸Boca Raton, Florida, United States
Tandem Clinical Research
🇺🇸Marrero, Louisiana, United States
National Research Institute - Santa Ana
🇺🇸Santa Ana, California, United States
South Texas Research Institute
🇺🇸Edinburg, Texas, United States
Doctors Hospital at Renaissance, LLC
🇺🇸McAllen, Texas, United States