Clinical trial NCT04702490: Study to Evaluate MET409 Alone or in Combination With Empagliflozin in Patients With Type 2 Diabetes and NASH
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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: NASH
NASH - Nonalcoholic Steatohepatitis
Type 2 Diabetes
Diabetes Type 2
Diabetes
Fatty Liver
Fatty Liver, Nonalcoholic
NAFLD
Keywords: NASH
FXR
Fatty Liver
Diabetes
Lead sponsor: Metacrine, Inc.
Sponsor class: INDUSTRY
First posted: 2021-01-11
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Safety and tolerability of MET409 with or without empagliflozin (incidence of adverse events)
timeFrame: Up to 28 days after last dose
Secondary outcomes:
measure: Pharmacological activity of MET409 alone or in combination with empagliflozin
timeFrame: 16 weeks
measure: Pharmacokinetic profile of MET409 alone or in combination with empagliflozin
timeFrame: 12 weeks
measure: Pharmacokinetic profile of MET409 alone or in combination with empagliflozin
timeFrame: 12 weeks
measure: Pharmacokinetic profile of MET409 alone or in combination with empagliflozin
timeFrame: 12 weeks
measure: Pharmacodynamic profile of MET409 alone or in combination with empagliflozin
timeFrame: 16 weeks
measure: Pharmacodynamic profile of MET409 alone or in combination with empagliflozin
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Fort Myers
country: United States
facility: Metacrine Investigative Site
state: Florida
city: San Antonio
country: United States
facility: Metacrine Investigative Site
state: Texas
Study officials:
affiliation: Metacrine, Inc.
name: Hubert C Chen, MD
role: STUDY_CHAIR
References: