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

NCT04702490 | Unknown Phase 2 FDA Drug

• 1 other identifier: MET409-201
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

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.

Conditions

NASH; NASH - Nonalcoholic Steatohepatitis; Type 2 Diabetes; Diabetes Type 2; Diabetes; Fatty Liver; Fatty Liver, Nonalcoholic; NAFLD

Keywords

NASH; FXR; Fatty Liver; Diabetes

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Pharmacological activity of MET409 alone or in combination with empagliflozin

  16 weeks

• Pharmacokinetic profile of MET409 alone or in combination with empagliflozin

  12 weeks

• Pharmacokinetic profile of MET409 alone or in combination with empagliflozin

  12 weeks

• Pharmacokinetic profile of MET409 alone or in combination with empagliflozin

  12 weeks

• Pharmacodynamic profile of MET409 alone or in combination with empagliflozin

  16 weeks

Study Arms (4)

MET409 A

EXPERIMENTAL

MET409 Active (50mg)

Drug: MET409 Active

MET409 P

PLACEBO COMPARATOR

MET409 Placebo (50mg)

Drug: MET409 Placebo

MET409A +Open-Label Empagliflozin

EXPERIMENTAL

MET409 Active (50mg) + Empagliflozin (10mg)

Drug: MET409 Active; Drug: Empagliflozin

MET409P +Open-Label Empagliflozin

PLACEBO COMPARATOR

MET409 Placebo (50mg) + Empagliflozin (10mg)

Drug: MET409 Placebo; Drug: Empagliflozin

Interventions

MET409 Active DRUG

MET409 Active (50mg)

MET409 A; MET409A +Open-Label Empagliflozin

MET409 Placebo DRUG

MET409 Placebo (50mg)

MET409 P; MET409P +Open-Label Empagliflozin

Empagliflozin DRUG

Empagliflozin (10mg)

MET409A +Open-Label Empagliflozin; MET409P +Open-Label Empagliflozin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Metacrine, Inc.: lead

Study Sites (2)

Metacrine Investigative Site

Fort Myers, Florida, 33907, United States

Location

Metacrine Investigative Site

San Antonio, Texas, 78215, United States

Location

Related Links

• Metacrine

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2; Diabetes Mellitus; Fatty Liver

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Hubert C Chen, MD

  Metacrine, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2021
• First Posted: January 11, 2021
• Study Start: December 15, 2020
• Primary Completion: April 1, 2022
• Study Completion: June 1, 2022
• Last Updated: June 1, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)