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

Diabetes Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04702490
• Other study ID #: MET409-201
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 15, 2020
• Est. completion date: June 2022

Study information

• Verified date: May 2021
• Source: Metacrine, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: June 2022
• Est. primary completion date: April 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetes Type 2
• Fatty Liver
• Fatty Liver, Nonalcoholic
• NAFLD
• NASH
• NASH - Nonalcoholic Steatohepatitis
• Non-alcoholic Fatty Liver Disease
• Type 2 Diabetes

Intervention

Drug:
• MET409 Active
MET409 Active (50mg)
• MET409 Placebo
MET409 Placebo (50mg)
• Empagliflozin
Empagliflozin (10mg)

Locations

Country	Name	City	State
United States	Metacrine Investigative Site	Fort Myers	Florida
United States	Metacrine Investigative Site	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Metacrine, Inc.

Country where clinical trial is conducted

United States, 

Outcome

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

External Links

•   Metacrine