Trial Outcomes & Findings for Study of Various Treatments in Non-alcoholic Fatty Liver Disease (NAFLD) Patients Who Have Aspects of Non-alcoholic Steatohepatitis (NASH) (NCT NCT04147195)

Participants were recruited from 10 sites in 3 countries.

Participants underwent a Screening period of up to 33 days followed by a Baseline assessment period of up to 27 days.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.