A Study of HTD1801 in Adults With Nonalcoholic Steatohepatitis (NASH) and Type 2 Diabetes Mellitus (T2DM)

The primary endpoint was the absolute change in liver fat content (LFC) as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) from Baseline to Week 18.

Change in fasting glucose from Baseline to Week 18 .

Changes in HbA1c from Baseline to Week 18.

Proportion of subjects who achieved ≥ 30% relative reduction in liver fat content (LFC) as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) from Baseline to Week 18.

Relative change in liver fat content (LFC) as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) from Baseline to Week 18.

Number of subjects who normalized liver fat content (LFC) to <5% as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) at Week 18.

Number of subjects who achieved ≥5% absolute reduction in liver fat content (LFC) as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) from Baseline to Week 18.

Change in homeostasis model assessment-estimated insulin resistance (HOMA-IR) from Baseline to Week 18. The higher the HOMA-IR score, the more insulin resistant a person is. Values of <1 are considered optimal while values >2.9 indicate significant insulin resistance.

Change in low-density lipoprotein cholesterol (LDL-c) from Baseline to Week 18.

Change in serum triglycerides from Baseline to Week 18.

Change in high-density lipoprotein cholesterol (HDL-c) from Baseline to Week 18.

Absolute change in aspartate aminotransferase (AST) from Baseline to Week 18.

Absolute change in alanine aminotransferase (ALT) from Baseline to Week 18.

Proportion of subjects with elevated alanine aminotransferase (ALT) at Baseline who normalized ALT at Week 18.

Change in Pro-C3 from Baseline to Week 18 for subjects with elevated Pro-C3 at Baseline.

Change in the enhanced liver fibrosis (ELF) score. The ELF score is calculated using a published algorithm combining the values of a set of extracellular matrix markers, including TIMP-1, PIIINP, and HA. The ELF score has been reported to show good correlations with fibrosis stages in chronic liver disease, with higher ELF scores associated with higher fibrosis stages. The ELF score is hence used as a prognostic marker for disease progression: ELF score < 9.8 : Low risk of progression, ELF score 9.8 to < 11.3 : Moderate risk of progression and ELF score > = 11.3 : High risk of progression.

Change in tissue inhibitor of metalloproteinases 1 (TIMP-1) from Baseline to Week 18.

Change in N-terminal pro-peptide of type III collagen (PIIINP) from Baseline to Week 18.

Change in hyaluronic acid (HA) from Baseline to Week 18.

Changes in total bile acids from Baseline to Week 18.

Change in fibroblast growth factor 19 (FGF19) from Baseline to Week 18

AEs were mapped to MedDRA version 20.1 preferred term (PT) and system organ class (SOC). If the subject experienced multiple events that mapped to a single preferred term, the greatest severity grade according to CTCAE Version 4.0, and strongest investigator assessment of relation to study medication was assigned to the preferred term. If an event had a missing severity or relationship, it was classified as having the highest severity and/or strongest relationship to study medication. The occurrence of TEAEs was summarized by treatment group by SOC, PT, and severity. Separate summaries of treatment-emergent serious adverse events (SAEs), TEAEs related to study drug, severe or life threatening TEAEs, and TEAEs leading to the discontinuation of study treatment were generated. Additionally, the occurrence of liver-specific AEs was summarized by treatment group. All reported adverse events were listed for individual subjects showing verbatim term, PT and SOC.