Study to Evaluate MET409 Alone or in Combination With Empagliflozin in Patients With Type 2 Diabetes and NASH

A Phase 2A Study to Evaluate MET409 Alone or in Combination With Empagliflozin in Patients With Type 2 Diabetes Mellitus (T2DM) and Nonalcoholic Steatohepatitis (NASH)

A randomized, multi-center study evaluating MET409 (50 mg) alone or in combination with empagliflozin (10 mg) for 12 weeks. Assignment to MET409 will be double-blind and placebo-controlled. Empagliflozin will be incorporated into two of the treatment arms in an open-label manner.

Subjects assigned to receive empagliflozin will be dosed at 10 mg per day for the duration of the study.

Approximately 30 subjects will be enrolled per treatment arm.

Key Inclusion Criteria:

• Males and females 18 through 75 years of age.
• Diagnosis of NASH based on NAFLD Activity Score (NAS) ≥ 4 with at least 1 point in each of steatosis, inflammation, and ballooning; Magnetic Resonance Elastography (MRE) showing kPa ≥ 2.61 or a multiparametric MRI (ie, LiverMultiScan) showing iron-corrected T1(cT1) > 830 ms within 6 months of enrollment; or Transient elastography (TE, FibroScan) with liver stiffness ≥ 8.5 kPa and controlled attenuation parameter (CAP) > 300 dB/m obtained within 3 months of enrollment.
• Liver fat content ≥ 8% measured by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) during screening.
• Diagnosis of T2DM for ≤ 10 years, with hemoglobin A1c ≤ 10.0% during screening, stable and controlled with diet or treatment for at least 3 months.

Key Exclusion Criteria:

• History of significant liver disease (eg, alcoholic liver disease, viral hepatitis, etc.) or liver transplant.
• Presence of cirrhosis on any prior liver biopsy (stage 4 fibrosis).
• Excessive consumption of alcohol.
• Use of any insulin (injectable or inhaled), SGLT-2 inhibitor or glucagon-like peptide 1 (GLP-1, injectable or oral) products for > 7 days within 3 months of screening.
• Weight loss > 10% in the 6 months prior to screening or > 5% during screening.
• Use of drugs historically associated with causing NAFLD for more than 4 consecutive weeks within 12 months prior to screening.
• Concomitant use of drugs that are strong or moderate CYP3A4 inhibitors.
• Concomitant consumption of grapefruit juice with the study drug.
• History of diabetic ketoacidosis (DKA) within 1 month prior to the Screening Visit, or more than 2 episodes within 6 months prior to the Screening Visit.
• History of > 2 episodes of urosepsis or pyelonephritis within 5 years of screening.