A Phase 2b Study of Icosabutate in Fatty Liver Disease (ICONA)

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study of NST-4016 in Patients With Nonalcoholic Steatohepatitis (NASH)

A Phase 2b study to evaluate the efficacy of different doses of NST-4016 on the resolution of NASH without worsening of fibrosis

Study Overview

• Status: Active, not recruiting
• Conditions: Non Alcoholic Steatohepatitis (NASH)
• Intervention / Treatment: Drug: Placebo; Drug: Icosabutate

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

• Study Type: Interventional
• Enrollment (Actual): 280
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00927-4807
    • Fundacion de Investigacion (FDI)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Central ResearchAssociates Inc.
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Arizona Liver Health
    • Glendale, Arizona, United States, 85306
      • Arizona Liver Health - Glendale
    • Tucson, Arizona, United States, 85712
      • Adobe Clinical Research, LLC
    • Tucson, Arizona, United States, 85711
      • Arizona Liver Health
  • Arkansas
    • North Little Rock, Arkansas, United States, 72117
      • Arkansas Gastroenterology - North Little Rock
  • California
    • Fresno, California, United States, 93720
      • Fresno Clinical Research Center
    • Huntington Park, California, United States, 90255
      • National Research Institute - Huntington Park
    • Los Angeles, California, United States, 90057
      • National Research Institute - Wilshire
    • Panorama City, California, United States, 91402
      • National Research Institute - Panorama
    • Poway, California, United States, 92064
      • Alliance Clinical Research
    • Santa Ana, California, United States, 92704
      • National Research Institute - Santa Ana
  • Colorado
    • Englewood, Colorado, United States, 80113
      • South Denver Gastroenterology
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Excel Medical Clinical Trials, LLC
    • Ocoee, Florida, United States, 34761
      • Sensible Healthcare LLC
    • Sarasota, Florida, United States, 34240
      • Covenant Research LLC
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Gastrointestinal Specialists of Georgia PC
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Texas Digestive Disease Consultants
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Gastrointestinal Associates, PA
    • Jackson, Mississippi, United States, 39216
      • Southern Therapy and Advanced Research LLC
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Research Institute
  • North Carolina
    • Fayetteville, North Carolina, United States, 28304
      • Cumberland Research Associates, LLC
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Aventiv Research, Inc.
  • Tennessee
    • Clarksville, Tennessee, United States, 37040
      • Premier Research
    • Germantown, Tennessee, United States, 38138
      • Gastro One
  • Texas
    • Austin, Texas, United States, 78746
      • Pinnacle Clinical Research
    • Dallas, Texas, United States, 75246
      • Texas Digestive Disease Consultants
    • Edinburg, Texas, United States, 78539
      • South Texas Research Institute
    • Houston, Texas, United States, 77030
      • Liver Associates of Texas
    • McAllen, Texas, United States, 78504
      • Doctors Hospital at Renaissance, LLC
    • San Antonio, Texas, United States, 78234
      • Brooke Army Medical Center
    • San Antonio, Texas, United States, 78229
      • Pinnacle Clinical Research
    • San Antonio, Texas, United States, 78209
      • Quality Research Inc
    • San Antonio, Texas, United States, 78215
      • American Research Corporation
    • Webster, Texas, United States, 77598
      • Texas Digestive Disease Consultants - Webster
  • Virginia
    • Richmond, Virginia, United States, 23249
      • Hunter Holmes McGuire VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo oral capsules taken one daily for 52 weeks	Drug: Placebo; Matching placebo oral capsule
Experimental: Icosabutate 300mg; Icosabutate 300mg oral capsule taken once daily for 52 weeks	Drug: Icosabutate; Icosabutate oral capsule once daily; Other Names: NST-4016
Experimental: Icosabutate 600mg; Icosabutate 600mg oral capsules taken once daily for 52 weeks	Drug: Icosabutate; Icosabutate oral capsule once daily; Other Names: NST-4016

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
Change from baseline in Nonalcoholic fatty liver disease (NAFLD) activity score (NAS)	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	52 weeks
Changes in individual histological scores for steatosis, ballooning, inflammation, and fibrosis from baseline	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	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 mg/dL from baseline		52 weeks

Collaborators and Investigators

• Sponsor: NorthSea Therapeutics B.V.

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2019
• Primary Completion (Anticipated): October 31, 2022
• Study Completion (Anticipated): January 30, 2023

Study Registration Dates

• First Submitted: August 7, 2019
• First Submitted That Met QC Criteria: August 8, 2019
• First Posted (Actual): August 9, 2019

Study Record Updates

• Last Update Posted (Actual): December 20, 2021
• Last Update Submitted That Met QC Criteria: December 17, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: NST-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No