Back to results

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

Primary Purpose

NASH, NASH - Nonalcoholic Steatohepatitis, Type 2 Diabetes

Status

Unknown status

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

MET409 Active

MET409 Placebo

Empagliflozin

About this trial

This is an interventional treatment trial for NASH focused on measuring NASH, FXR, Fatty Liver, Diabetes

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Metacrine Investigative Site
Metacrine Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

MET409 A

MET409 P

MET409A +Open-Label Empagliflozin

MET409P +Open-Label Empagliflozin

Arm Description

MET409 Active (50mg)

MET409 Placebo (50mg)

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Pharmacological activity of MET409 alone or in combination with empagliflozin

Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF)

Pharmacokinetic profile of MET409 alone or in combination with empagliflozin

Cmax

Pharmacokinetic profile of MET409 alone or in combination with empagliflozin

tmax

Pharmacokinetic profile of MET409 alone or in combination with empagliflozin

AUClast

Pharmacodynamic profile of MET409 alone or in combination with empagliflozin

Bile acid precursor : C4 (7αhydroxy-4-cholesten-3-one)

Pharmacodynamic profile of MET409 alone or in combination with empagliflozin

Bile acid precursor : Fibroblast growth factor 19 (FGF19)

Full Information

NCT ID

NCT04702490

First Posted

January 4, 2021

Last Updated

May 28, 2021

Sponsor

Metacrine, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT04702490

Brief Title

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

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Unknown status

Study Start Date

December 15, 2020 (Actual)

Primary Completion Date

April 2022 (Anticipated)

Study Completion Date

June 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Metacrine, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

NASH, FXR, Fatty Liver, Diabetes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

120 (Actual)

8. Arms, Groups, and Interventions

Arm Title

MET409 A

Arm Type

Experimental

Arm Description

MET409 Active (50mg)

Arm Title

MET409 P

Arm Type

Placebo Comparator

Arm Description

MET409 Placebo (50mg)

Arm Title

MET409A +Open-Label Empagliflozin

Arm Type

Experimental

Arm Description

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

Arm Title

MET409P +Open-Label Empagliflozin

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

MET409 Active

Intervention Description

MET409 Active (50mg)

Intervention Type

Drug

Intervention Name(s)

MET409 Placebo

Intervention Description

MET409 Placebo (50mg)

Intervention Type

Drug

Intervention Name(s)

Empagliflozin

Intervention Description

Empagliflozin (10mg)

Primary Outcome Measure Information:

Title

Safety and tolerability of MET409 with or without empagliflozin (incidence of adverse events)

Description

Incidence of Treatment-emergent adverse events, incidence of clinically significant changes in vital signs, abnormal laboratory safety tests, and abnormal ECGs.

Time Frame

Up to 28 days after last dose

Secondary Outcome Measure Information:

Title

Pharmacological activity of MET409 alone or in combination with empagliflozin

Description

Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF)

Time Frame

16 weeks

Title

Pharmacokinetic profile of MET409 alone or in combination with empagliflozin

Description

Cmax

Time Frame

12 weeks

Title

Pharmacokinetic profile of MET409 alone or in combination with empagliflozin

Description

tmax

Time Frame

12 weeks

Title

Pharmacokinetic profile of MET409 alone or in combination with empagliflozin

Description

AUClast

Time Frame

12 weeks

Title

Pharmacodynamic profile of MET409 alone or in combination with empagliflozin

Description

Bile acid precursor : C4 (7αhydroxy-4-cholesten-3-one)

Time Frame

16 weeks

Title

Pharmacodynamic profile of MET409 alone or in combination with empagliflozin

Description

Bile acid precursor : Fibroblast growth factor 19 (FGF19)

Time Frame

16 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hubert C Chen, MD

Organizational Affiliation

Metacrine, Inc.

Official's Role

Study Chair

Facility Information:

Facility Name

Metacrine Investigative Site

City

Fort Myers

State/Province

Florida

ZIP/Postal Code

33907

Country

United States

Facility Name

Metacrine Investigative Site

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78215

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Links:

URL

https://www.metacrine.com/

Description

Metacrine

Learn more about this trial

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

We'll reach out to this number within 24 hrs