AzTrials
AzTrials

Non-alcoholic Fatty Liver DiseasePhase 2NEXSCOTNCT04147195

Study of Various Treatments in Non-alcoholic Fatty Liver Disease (NAFLD) Patients Who Have Aspects of Non-alcoholic Steatohepatitis (NASH)

A Phase 2 study testing LYS006 and Tropifexor in people with Non-alcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis, run by Novartis Pharmaceuticals at 10 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This clinical study was designed to evaluate the safety, tolerability, pharmacokinetics and efficacy of various single and combination treatments in adult patients with non-alcoholic fatty liver disease (NAFLD) who manifest a non-alcoholic steatohepatitis (NASH)-like biomarker phenotype. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
LYS006 and Tropifexor
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
10 sitesin 3 countries
Study dates
4 Jun 2020to 6 Jan 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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Phenotypic diagnosis of NASH based on the presence of all of the following:
  • ALT ≥ 43 IU/L (males) or ≥ 28 IU/L (females)
  • BMI ≥ 27 kg/m2 (race other than Asian) or ≥ 23 kg/m2 (Asian race)
  • History of type 2 diabetes mellitus with HbA1c ≤ 9%
  • ELF test score ≥ 8.5 and ≤ 10.5
  • Liver fat ≥ 8%
  • Patients must weigh between 40 kg (88 lbs.) and 150 kg (330 lbs.)

Who cannot join

  • Use of other investigational drugs within 5 half-lives of randomization or within 3 months, whichever is longer
  • Use of obeticholic acid (OCA) or pharmacologically-active weight loss drugs within 1 month of randomization
  • Use of strong CYP3A4/5 inhibitors or strong CYP3A4 inducers within 5 half-lives or 7 days of randomization, whichever is longer
  • History or presence of other concomitant liver diseases
  • History or current diagnosis of ECG abnormalities
  • Patients with contraindications to MRI imaging
Show all 11Show fewer
  • Current or history of significant alcohol consumption
  • Clinical evidence of hepatic decompensation or severe liver impairment
  • Women of child bearing potential (unless on highly effective methods of contraception)
  • Presence of liver cirrhosis
  • Use of OAT3 inhibitors within 5 half-lives or 7 days of randomization, whichever is longer

Trial locations and contacts

10 sites in 3 countries.

10 sites in 3 countries

United States8 sites
  • Novartis Investigative Site

    Coronado, California, 92118

  • Novartis Investigative Site

    Honolulu, Hawaii, 96814

  • Novartis Investigative Site

    Los Angeles, California, 90057

  • Novartis Investigative Site

    Marietta, Georgia, 30060

  • Novartis Investigative Site

    Miami Lakes, Florida, 33014

  • Novartis Investigative Site

    Morehead City, North Carolina, 28557

  • Novartis Investigative Site

    San Antonio, Texas, 78215

  • Novartis Investigative Site

    South Bend, Indiana, 46635

Other trials in United States

Argentina1 site
  • Novartis Investigative Site

    Buenos Aires, C1012AAR

Other trials in Argentina

Germany1 site
  • Novartis Investigative Site

    Essen, Nordrhine Westphalia, 45136

Other trials in Germany

About this study

Official title: NASH EXploratory Single and COmbination Treatment (NEXSCOT): An Open Label, Multicenter, Platform Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Various Single and Combination Treatments in Patients With Non-alcoholic Fatty Liver Disease (NAFLD) Who Manifest a Non-alcoholic Steatohepatitis (NASH)-Like Biomarker Phenotype

This clinical study was designed to evaluate the safety, tolerability, pharmacokinetics and efficacy of various single and combination treatments in adult patients with non-alcoholic fatty liver disease (NAFLD) who manifest a non-alcoholic steatohepatitis (NASH)-like biomarker phenotype.

Read the detailed description

This was a Phase II, non-confirmatory, multicenter, open label, platform study in NAFLD participants with a NASH-like biomarker phenotype to examine the effects of single and combination therapies over 12 weeks of treatment. The study consisted of four distinct study periods:

  • Screening Period (Day -60 to -28): Lasted up to a maximum of 33 days where participants were assessed for inclusion and exclusion criteria prior the baseline assessments.
  • Baseline Period (Day -27 to -1): Lasted up to a maximum of 27 days and comprised baseline assessments and randomization.
  • Treatment Period (Day 1 to 85): Participants were randomized in a 1:1 ratio to LYS006 20 mg (twice a day) arm or to LYS006 20 mg (twice a day) and tropifexor 200ug (once a day). Participants were treated daily during 12 weeks.
  • Follow-up Period (Day 85 to 113): After completion of the treatment period, participants were observed until the End Of Study (EOS) visit at Day 113.
Being tested
LYS006, Tropifexor
Keywords
Non-alcoholic fatty liver disease, NAFLD, Non-alcoholic steatohepatitis, NASH, Platform design, LYS006, LJN452, Tropifexor
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.

  • LYS006Drug

    5 mg LYS006 capsules orally administered 20 mg b.i.d for 12 weeks

  • TropifexorDrug

    Also called LJN452

    100 ug LJN452 capsules orally administered 200ug once daily for 12 weeks

Study groups in NCT04147195
Study groupRoleWhat they receive
LYS006ExperimentalLYS006 20 mg was administered orally twice per day (b.i.d) for 12 weeks
Receives: Drug: LYS006
LYS006 + LJN452ExperimentalLYS006 20 mg was administered orally twice per day (b.i.d) in addition to LJN452 200ug administered orally once daily for 12 weeks
Receives: Drug: Tropifexor

What is being measured

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

  1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Number of participants with AEs and SAEs including significant changes from baseline in vital signs, electrocardiograms and laboratory parameters qualifying and reported as AEs. The number of participants in each category is reported in the table.

    Measured: From the start of treatment to 28 days after end of treatment, assessed up to maximum duration of 113 Days

Secondary outcomes (12)
  1. Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score

    The markers of fibrosis assessed in this test comprised hyaluronic acid (HA), tissue inhibitor of metalloproteinase (TIMP1) and procollagen III N-terminal peptide (PIIINP); these are components of the extracellular matrix and basement sinusoidal membrane of the liver and are elevated during fibrogenesis as a result of activation of the hepatic stellate cell. The ELF test is a composite score: < 7.7: no to mild fibrosis; ≥ 7.7 - < 9.8: Moderate fibrosis; ≥ 9.8 - < 11.3: Severe fibrosis; ≥ 11.3: Cirrhosis.

    Baseline is defined as the last non-missing measurement taken at the Screening and Baseline visits (prior to the first dose of study drug administered at the Day 1). A negative change from Baseline indicates decreased fibrosis.

    Measured: Baseline and Days 57, 85 and EOS (Day 113)

  2. Change From Baseline in Cholesterol: Fasting Lipid Profile Endpoint

    Fasting lipid profile (total cholesterol) was examined as a cardiometabolic risk parameter. Total cholesterol was measured on blood samples under fasted conditions and analyzed at a central laboratory.

    Baseline is defined as the last non-missing measurement taken at the Screening and Baseline visits (prior to the first dose of study drug administered at the Day 1). A negative change from Baseline indicates cardiovascular risk.

    Measured: Baseline and Days 15, 29, 43, 57, 85 and EOS (Day 113)

  3. Change From Baseline in Percent Liver Fat at Day 85

    Percent (%) Liver fat was measured by Magnetic Resonance Imaging Proton Density Liver Fat Fraction (MRIPDFF). Participants underwent magnetic resonance imaging twice during the course of the study (baseline and end of treatment) to quantitate liver fat.

    Baseline is defined as the last non-missing measurement taken at the Screening and Baseline visits (prior to the first dose of study drug administered at the Day 1). A negative change from Baseline indicates a reduction in a component of NAFLD.

    Measured: Baseline and Day 85

  4. Change From Baseline in Total Body Weight

    Body weight (to the nearest 0.1 kilogram [kg] was measured on a calibrated scale. The measurement was performed with the study participant in underwear and without shoes; or while wearing minimal indoor clothing.

    Baseline is defined as the last non-missing measurement taken at the Screening and Baseline visits (prior to the first dose of study drug administered at the Day 1). A negative change from Baseline indicates improvement in obesity.

    Measured: Baseline and Days 15, 29, 43, 57, 85 and EOS (Day 113)

  5. Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Day 85

    HOMA-IR is a test that uses a simultaneous fasting blood glucose test and fasting insulin test to accurately estimate the degree of insulin resistance (IR) and β-cell function (the cells of the pancreas that produce insulin). HOMA-IR scores are classified as follows: Insulin sensitive is considered less than 1.0, Healthy is considered 0.5-1.4, Above 1.8 is early insulin resistance and Above 2.7 is considered significant insulin resistance

    HOMA-IR= [Fasting glucose (mmol/L) x (fasting insulin (pmol/L)/6)] / 22.5

    Baseline is defined as the last non-missing measurement taken at the Screening and Baseline visits (prior to the first dose of study drug administered at the Day 1). A negative change from Baseline indicates improvement in insulin sensitivity.

    Measured: Baseline and Day 85

  6. Change From Baseline in Fasting Glucose

    Fasting Glucose was examined as a cardiometabolic risk parameter. Total fasting glucose was measured on blood samples under fasted conditions and analyzed at a central laboratory.

    Baseline is defined as the last non-missing measurement taken at the Screening and Baseline visits (prior to the first dose of study drug administered at the Day 1). A negative change from Baseline indicates improvement in glycemic control.

    Measured: Baseline and Days 15, 29, 43, 57, 85 and EOS (Day 113)

  7. Change From Baseline in Fasting Insulin at Day 85

    Fasting insulin was examined as a cardiometabolic risk parameter. Total fasting insulin was measured on blood samples under fasted conditions and analyzed at a central laboratory.

    Baseline is defined as the last non-missing measurement taken at the Screening and Baseline visits (prior to the first dose of study drug administered at the Day 1). A negative change from Baseline indicates improvement in insulin sensitivity.

    Measured: Baseline and Day 85

  8. Change From Baseline in Hemoglobin A1c (HbA1c)

    HbA1c was examined as a cardiometabolic risk parameter. HbA1c was measured on blood samples under fasted conditions and analyzed at a central laboratory.

    Baseline is defined as the last non-missing measurement taken at the Screening and Baseline visits (prior to the first dose of study drug administered at the Day 1). A negative change from Baseline indicates improvement in glycemic control.

    Measured: Baseline and Days 15, 29, 43, 57, 85 and EOS (Day 113)

  9. Change From Baseline in Alanine Aminotransferase (ALT)

    Alanine aminotransferase (ALT) is an enzyme found primarily in the liver. ALT is increased with liver damage. In this study, the blood levels of ALT was used to detect liver inflammation.

    Baseline is defined as the mean of the last 2 non-missing measurements taken at the Screening and Baseline visits (prior to the first dose of study drug administered at the Day 1). A negative change from Baseline indicates a reduction in liver inflammation.

    Measured: Baseline and days 15, 29, 43, 57, 85 and EOS (Day 113)

  10. Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)

    High-sensitivity C-reactive protein is a blood test marker for inflammation in the body. HsCRP was measured from a blood sample and analyzed at a central laboratory.

    Baseline is defined as the last non-missing measurement taken at the Screening and Baseline visits (prior to the first dose of study drug administered at the Day 1). A negative change from Baseline indicates a reduction in liver inflammation.

    Measured: Baseline and Days 57, 85 and EOS (Day 113)

  11. LYS006 Plasma Concentration

    LYS006 plasma concentrations were determined by a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. No methods for imputation of missing data were used.

    Measured: pre-dose at Days 1, 29, 57 and 85 and post-dose (1, 2, 3 and 4 hours) at Days 29 and 57

  12. Maximum Observed Plasma Concentration (Cmax) of LYS006

    LYS006 plasma concentrations were determined by a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. Cmax of LYS006 was determined with Phoenix WinNonlin (Version 8.0 or higher). No methods for imputation of missing data were used.

    Measured: pre-dose and post-dose (1, 2, 3 and 4 hours) at Days 29 and 57

Timeline

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

  1. First posted1 Nov 2019
  2. Study start4 Jun 2020
  3. Primary completion6 Jan 2022
  4. Study completion6 Jan 2022

Why it stopped: Sponsor Decision

Resources

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
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04147195
Sponsor's protocol ID
CADPT02A12001
Other IDs
2018-002692-17, 2018
Acronym
NEXSCOT
Status last verified
Aug 2023
First submitted
22 Oct 2019
Last updated
21 Aug 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Publications

  • Frias J, Schmouder R, Lawitz E, Zhang Y, Zhou H, Badman MK, Ukomadu C, Weiss HM, Zack J, Yadav B, Martic M, Drakeford C, Koo P, Naoumov NV, Greenbaum LE. Clinical trial: A Phase 2 Randomised Platform Study to Assess Monotherapy and Combination Treatment Regimens in Metabolic Dysfunction-Associated Steatohepatitis. Aliment Pharmacol Ther. 2026 Mar;63(5):637-647. doi: 10.1111/apt.70475. Epub 2025 Nov 26.

    PubMed 41305844

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LYS006 and Tropifexor in people with Non-alcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis, run by Novartis Pharmaceuticals at 10 sites in 3 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 7 inclusion and 11 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: stopped early, as of the sponsor's last update on 21 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States, Argentina, Germany. 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. 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 26 Jan 2023). 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?

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: From the start of treatment to 28 days after end of treatment, assessed up to maximum duration of 113 Days). 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 NCT04147195, 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 21 Aug 2023.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in