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.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetes; Fatty Liver; Type 2 Diabetes; NAFLD; NASH - Nonalcoholic Steatohepatitis; Diabetes Type 2; NASH; Fatty Liver, Nonalcoholic
• Intervention / Treatment: Drug: MET409 Active; Drug: MET409 Placebo; Drug: Empagliflozin

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 Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Fort Myers, Florida, United States, 33907
      • Metacrine Investigative Site
  • Texas
    • San Antonio, Texas, United States, 78215
      • Metacrine Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MET409 A; MET409 Active (50mg)	Drug: MET409 Active; MET409 Active (50mg)
Placebo Comparator: MET409 P; MET409 Placebo (50mg)	Drug: MET409 Placebo; MET409 Placebo (50mg)
Experimental: MET409A +Open-Label Empagliflozin; MET409 Active (50mg) + Empagliflozin (10mg)	Drug: MET409 Active; MET409 Active (50mg); Drug: Empagliflozin; Empagliflozin (10mg)
Placebo Comparator: MET409P +Open-Label Empagliflozin; MET409 Placebo (50mg) + Empagliflozin (10mg)	Drug: MET409 Placebo; MET409 Placebo (50mg); Drug: Empagliflozin; Empagliflozin (10mg)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacological activity of MET409 alone or in combination with empagliflozin	Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF)	16 weeks
Pharmacokinetic profile of MET409 alone or in combination with empagliflozin	Cmax	12 weeks
Pharmacokinetic profile of MET409 alone or in combination with empagliflozin	tmax	12 weeks
Pharmacokinetic profile of MET409 alone or in combination with empagliflozin	AUClast	12 weeks
Pharmacodynamic profile of MET409 alone or in combination with empagliflozin	Bile acid precursor : C4 (7αhydroxy-4-cholesten-3-one)	16 weeks
Pharmacodynamic profile of MET409 alone or in combination with empagliflozin	Bile acid precursor : Fibroblast growth factor 19 (FGF19)	16 weeks

Collaborators and Investigators

• Sponsor: Metacrine, Inc.
• Investigators: Study Chair: Hubert C Chen, MD, Metacrine, Inc.

Publications and helpful links

Helpful Links

• Metacrine

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2020
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): June 1, 2022

Study Registration Dates

• First Submitted: January 4, 2021
• First Submitted That Met QC Criteria: January 8, 2021
• First Posted (Actual): January 11, 2021

Study Record Updates

• Last Update Posted (Actual): June 1, 2021
• Last Update Submitted That Met QC Criteria: May 28, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Diabetes; NASH; Fatty Liver; FXR
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Liver Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Liver; Non-alcoholic Fatty Liver Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: MET409-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No