Diabetes, Diabetes Type 2, Fatty Liver, Fatty Liver, Nonalcoholic, NAFLD, NASH, NASH - Nonalcoholic Steatohepatitis, Type 2 Diabetes
Conditions
Keywords
NASH, FXR, Fatty Liver, Diabetes
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.
Interventions
DRUGMET409 Active
MET409 Active (50mg)
DRUGMET409 Placebo
MET409 Placebo (50mg)
DRUGEmpagliflozin
Empagliflozin (10mg)
Sponsors
Metacrine, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Pharmacodynamic profile of MET409 alone or in combination with empagliflozin | 16 weeks | Bile acid precursor : C4 (7αhydroxy-4-cholesten-3-one) |
Countries
United States
Outcome results
None listed