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

Phase 2

• Conditions: Fatty Liver; Type 2 Diabetes; Diabetes Type 2; Diabetes; NAFLD; NASH; NASH - Nonalcoholic Steatohepatitis; Fatty Liver, Nonalcoholic
• Interventions: Drug: MET409 Active; Drug: MET409 Placebo; Drug: Empagliflozin

• Registration Number: NCT04702490
• Lead Sponsor: Metacrine, Inc.

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2020-12-15
• Study First Submitted: 2021-01-04
• Study First Submitted QC: 2021-01-08
• Study First Posted: 2021-01-11
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-28
• Last Update Posted: 2021-06-01
• Primary Completion: 2022-04
• Study Completion: 2022-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MET409A +Open-Label Empagliflozin	MET409 Active	MET409 Active (50mg) + Empagliflozin (10mg)
MET409P +Open-Label Empagliflozin	MET409 Placebo	MET409 Placebo (50mg) + Empagliflozin (10mg)
MET409 P	MET409 Placebo	MET409 Placebo (50mg)
MET409 A	MET409 Active	MET409 Active (50mg)
MET409A +Open-Label Empagliflozin	Empagliflozin	MET409 Active (50mg) + Empagliflozin (10mg)
MET409P +Open-Label Empagliflozin	Empagliflozin	MET409 Placebo (50mg) + Empagliflozin (10mg)

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of MET409 with or without empagliflozin (incidence of adverse events)	Up to 28 days after last dose	Incidence of Treatment-emergent adverse events, incidence of clinically significant changes in vital signs, abnormal laboratory safety tests, and abnormal ECGs.

Secondary Outcome Measures

Name	Time	Method
Pharmacological activity of MET409 alone or in combination with empagliflozin	16 weeks	Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF)
Pharmacodynamic profile of MET409 alone or in combination with empagliflozin	16 weeks	Bile acid precursor : Fibroblast growth factor 19 (FGF19)
Pharmacokinetic profile of MET409 alone or in combination with empagliflozin	12 weeks	AUClast

Trial Locations

Locations (1)

Metacrine Investigative Site; 🇺🇸 San Antonio, Texas, United States