Non Alcoholic Steatohepatitis (NASH)Phase 2ICONANCT04052516

A Phase 2b Study of Icosabutate in Fatty Liver Disease

A Phase 2 study testing Icosabutate in people with Non Alcoholic Steatohepatitis (NASH), run by NorthSea Therapeutics B.V. at 39 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Non Alcoholic Steatohepatitis (NASH)
What is being tested?: Icosabutate
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 280 participants
Where: 39 sitesin 2 countries
Study dates: 17 Jul 2019to 19 Dec 2022
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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)

Show all 9Show fewer

Has type 1 diabetes mellitus
Has diabetic ketoacidosis
Has a history of liver decompensation

Trial locations and contacts

39 sites in 2 countries.

Country

City, postcode or hospital

39 sites in 2 countries

United States38 sites

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

Other trials in United States

Puerto Rico1 site

Fundacion de Investigacion (FDI)
San Juan, 00927-4807

Other trials in Puerto Rico

About this study

Official title: 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

Read the 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

Conditions: Non Alcoholic Steatohepatitis (NASH)
Being tested: Icosabutate, Placebo
Medical subject headings: Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

IcosabutateDrug
Also called NST-4016
Icosabutate oral capsule once daily
PlaceboDrug
Matching placebo oral capsule

Study groups in NCT04052516
Study group	Role	What they receive
Placebo	Placebo comparator	Placebo oral capsules taken one daily for 52 weeks Receives: Drug: Placebo
Icosabutate 300mg	Experimental	Icosabutate 300mg oral capsule taken once daily for 52 weeks Receives: Drug: Icosabutate
Icosabutate 600mg	Experimental	Icosabutate 600mg oral capsules taken once daily for 52 weeks Receives: Drug: Icosabutate

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 52 weeks

Secondary outcomes (12)

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).
Measured: 52 weeks
Percentage of Patients With Fibrosis Improvement, Defined as Greater Than or Equal to 1 Stage of Fibrosis Improvement.
Measured: 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
Measured: 52 weeks
Change in Bilirubin Micromol/L From Baseline
Measured: 52 weeks
Change From Baseline in Inflammation Marker hsCRP
Measured: 52 weeks
Change From Baseline in Fibrosis Activity Marker Pro-C3
Measured: 52 weeks
Change From Baseline in Fibrosis Activity Marker Enhanced Liver Fibrosis (ELF) Test
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.
Measured: 52 weeks
Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
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.
Measured: 52 weeks
Change From Baseline in Composite Disease Activity Score (Composite NASH Score of Inflammation, Ballooning, Fibrosis)
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.
Measured: 52 weeks
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
Measured: 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
Measured: 52 weeks
Change From Baseline in Magnetic Resonance Imaging-Proton Density-Fat Fraction (MRI-PDFF)
MRI-PDFF is a quantitative imaging biomarker that measures the fat fraction of tissue by correcting factors influencing magnetic resonance signal intensity.
Measured: 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

17 Jul 201919 Dec 2022

First posted9 Aug 2019
Study start17 Jul 2019
Primary completion20 Feb 2022
Study completion19 Dec 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Non Alcoholic Steatohepatitis (NASH)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 280 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04052516
Sponsor's protocol ID: NST-02
Acronym: ICONA
Status last verified: Feb 2025
First submitted: 7 Aug 2019
Last updated: 28 Feb 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Harrison SA, Alkhouri N, Ortiz-Lasanta G, Rudraraju M, Tai D, Wack K, Shah A, Besuyen R, Steineger HH, Fraser DA, Sanyal AJ; ICONA Study Investigators. A phase IIb randomised-controlled trial of the FFAR1/FFAR4 agonist icosabutate in MASH. J Hepatol. 2025 Aug;83(2):293-303. doi: 10.1016/j.jhep.2025.01.032. Epub 2025 Feb 10.
PubMed 39938653

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Efficacy of Carnitine Complex in Improving Hepatic Steatosis in Potential Liver Donors
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RecruitingPhase 3
A Study Evaluating Efruxifermin in Subjects With Non-Cirrhotic Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis
NASH With Fibrosis, MASH With Fibrosis
Recruiting
NAFLD Clinical Care Pathway
NAFLD, MASLD
RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD
RecruitingPhase 1
A Study of Efimosfermin Alfa in Adults With Hepatic Impairment
Non-alcoholic Fatty Liver Disease

All Non Alcoholic Steatohepatitis (NASH) trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study of NST-4016 in Patients With Nonalcoholic Steatohepatitis (NASH)
ClinicalTrials.gov ID: NCT04052516
Acronym / sponsor ID: ICONA / NST-02
Conditions: Non Alcoholic Steatohepatitis (NASH)
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 280 participants (actual)
Lead sponsor: NorthSea Therapeutics B.V.Industry (pharma, biotech, devices)
Study start: 17 Jul 2019 (actual)
Primary completion: 20 Feb 2022 (actual)
Study completion: 19 Dec 2022 (actual)
First posted: 9 Aug 2019 (actual)
Results: Posted 28 Feb 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Placebo	Placebo comparator	Drug: PlaceboPlacebo oral capsules taken one daily for 52 weeks
Icosabutate 300mg	Experimental	Drug: IcosabutateIcosabutate 300mg oral capsule taken once daily for 52 weeks
Icosabutate 600mg	Experimental	Drug: IcosabutateIcosabutate 600mg oral capsules taken once daily for 52 weeks

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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%),

Key exclusion criteria (9 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
IcosabutateAlso: NST-4016Icosabutate oral capsule once daily	Drug	Icosabutate 300mg, Icosabutate 600mg
PlaceboMatching placebo oral capsule	Drug	Placebo

Primary outcome

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.
Time frame: 52 weeks

12 secondary outcomes

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).
Time frame: 52 weeks
Percentage of Patients With Fibrosis Improvement, Defined as Greater Than or Equal to 1 Stage of Fibrosis Improvement.
Time frame: 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
Time frame: 52 weeks
Change in Bilirubin Micromol/L From Baseline
Time frame: 52 weeks
Change From Baseline in Inflammation Marker hsCRP
Time frame: 52 weeks
Change From Baseline in Fibrosis Activity Marker Pro-C3
Time frame: 52 weeks
Change From Baseline in Fibrosis Activity Marker Enhanced Liver Fibrosis (ELF) Test
Time frame: 52 weeks
Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
Time frame: 52 weeks
Change From Baseline in Composite Disease Activity Score (Composite NASH Score of Inflammation, Ballooning, Fibrosis)
Time frame: 52 weeks
Change From Baseline in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)
Time frame: 52 weeks
Changes in Individual Histological Scores for Steatosis, Ballooning, Inflammation, and Fibrosis From Baseline
Time frame: 52 weeks
Change From Baseline in Magnetic Resonance Imaging-Proton Density-Fat Fraction (MRI-PDFF)
Time frame: 52 weeks

Results and safety

Results posted to the registry on 28 Feb 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	92	79
Icosabutate 300mg	93	78
Icosabutate 600mg	95	78

Primary outcome: 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.

Time frame: 52 weeks. Number. Unit: percentage of participants

Measure	Placebo n = 46	Icosabutate 300mg n = 52	Icosabutate 600mg n = 53
Value	8.7	17.3	20.8

Placebo vs Icosabutate 300mg: Odds Ratio (OR): 1.70 (95% CI 0.62 to 4.63), p = 0.2991, Cochran-Mantel-Haenszel
Placebo vs Icosabutate 600mg: Odds Ratio (OR): 2.01 (95% CI 0.80 to 5.08), p = 0.1386, Cochran-Mantel-Haenszel

Population analysed: 3-Panel Modified Intent-To-Treat (mITT) Population - The 3-Panel mITT Population included all patients who had a baseline and Week 52 (or ET, if applicable) liver biopsy read and fulfilled eligibility criteria based on the 3-panel read paradigm. This population was considered the primary population for the efficacy analysis of the histology data. Biopsy fibrosis score F2/F3

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).. Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	4 of 91 (4.4%)	82 of 91 (90.1%)	1 of 91
Icosabutate 300mg	5 of 92 (5.4%)	80 of 92 (87%)	0 of 92
Icosabutate 600mg	8 of 95 (8.4%)	80 of 95 (84.2%)	1 of 95

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39938653Harrison SA, Alkhouri N, Ortiz-Lasanta G, Rudraraju M, Tai D, Wack K, Shah A, Besuyen R, Steineger HH, Fraser DA, Sanyal AJ; ICONA Study Investigators. A phase IIb randomised-controlled trial of the FFAR1/FFAR4 agonist icosabutate in MASH. J Hepatol. 2025 Aug;83(2):293-303. doi: 10.1016/j.jhep.2025.01.032. Epub 2025 Feb 10.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

39 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Icosabutate in people with Non Alcoholic Steatohepatitis (NASH), run by NorthSea Therapeutics B.V. at 39 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 39 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: 52 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04052516, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2025.