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

Sponsor

Metacrine, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04702490

Collaborator

(none)

120

Enrollment

Locations

Arms

17.5

Anticipated Duration (Months)

Patients Per Site

3.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
NASH NASH - Nonalcoholic Steatohepatitis Type 2 Diabetes Diabetes Type 2 Diabetes Fatty Liver Fatty Liver, Nonalcoholic NAFLD	Drug: MET409 Active Drug: MET409 Placebo Drug: Empagliflozin	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Dec 15, 2020

Anticipated Primary Completion Date :

Apr 1, 2022

Anticipated Study Completion Date :

Jun 1, 2022

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.