NASHPhase 2NCT04702490
Study to Evaluate MET409 Alone or in Combination With Empagliflozin in Patients With Type 2 Diabetes and NASH
A Phase 2 study testing MET409 Active and Empagliflozin in people with NASH and NASH - Nonalcoholic Steatohepatitis, run by Metacrine, Inc. at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- NASH, NASH - Nonalcoholic Steatohepatitis, Type 2 Diabetes
- What is being tested?
- MET409 Active and Empagliflozin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 2 sitesUnited States
- Study dates
- 15 Dec 2020to Jun 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Metacrine Investigative Site
Fort Myers, Florida, 33907
Metacrine Investigative Site
San Antonio, Texas, 78215
About this study
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)
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.
Read the 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.
- Conditions
- NASH, NASH - Nonalcoholic Steatohepatitis, Type 2 Diabetes, Diabetes Type 2, Diabetes, Fatty Liver
- Being tested
- MET409 Active, MET409 Placebo, Empagliflozin
- Keywords
- NASH, FXR, Fatty Liver, Diabetes
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Diabetes Mellitus, Type 2, Diabetes Mellitus, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MET409 ActiveDrug
MET409 Active (50mg)
MET409 PlaceboDrug
MET409 Placebo (50mg)
EmpagliflozinDrug
Empagliflozin (10mg)
| Study group | Role | What they receive |
|---|---|---|
| MET409 A | Experimental | MET409 Active (50mg) Receives: Drug: MET409 Active |
| MET409 P | Placebo comparator | MET409 Placebo (50mg) Receives: Drug: MET409 Placebo |
| MET409A +Open-Label Empagliflozin | Experimental | MET409 Active (50mg) + Empagliflozin (10mg) Receives: Drug: MET409 Active; Drug: Empagliflozin |
| MET409P +Open-Label Empagliflozin | Placebo comparator | MET409 Placebo (50mg) + Empagliflozin (10mg) Receives: Drug: MET409 Placebo; Drug: Empagliflozin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 28 days after last dose
Secondary outcomes (6)
Pharmacological activity of MET409 alone or in combination with empagliflozin
Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF)
Measured: 16 weeks
Pharmacokinetic profile of MET409 alone or in combination with empagliflozin
Cmax
Measured: 12 weeks
Pharmacokinetic profile of MET409 alone or in combination with empagliflozin
tmax
Measured: 12 weeks
Pharmacokinetic profile of MET409 alone or in combination with empagliflozin
AUClast
Measured: 12 weeks
Pharmacodynamic profile of MET409 alone or in combination with empagliflozin
Bile acid precursor : C4 (7αhydroxy-4-cholesten-3-one)
Measured: 16 weeks
Pharmacodynamic profile of MET409 alone or in combination with empagliflozin
Bile acid precursor : Fibroblast growth factor 19 (FGF19)
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2021
- Study start15 Dec 2020
- Primary completionApr 2022 (estimated)
- Study completionJun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NASHStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Metacrine, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Hubert C Chen, MD, Study chair, Metacrine, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04702490
- Sponsor's protocol ID
- MET409-201
- Status last verified
- May 2021
- First submitted
- 4 Jan 2021
- Last updated
- 1 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04702490
- Acronym / sponsor ID
- MET409-201
- Conditions
- NASH, NASH - Nonalcoholic Steatohepatitis, Type 2 Diabetes, Diabetes Type 2, Diabetes, Fatty Liver
- Keywords
- NASH, FXR, Fatty Liver, Diabetes
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Metacrine, Inc.Industry (pharma, biotech, devices)
- Study start
- 15 Dec 2020 (actual)
- Primary completion
- Apr 2022 (estimated)
- Study completion
- Jun 2022 (estimated)
- First posted
- 11 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| MET409 A | Experimental | Drug: MET409 ActiveMET409 Active (50mg) |
| MET409 P | Placebo comparator | Drug: MET409 PlaceboMET409 Placebo (50mg) |
| MET409A +Open-Label Empagliflozin | Experimental | Drug: MET409 Active, Drug: EmpagliflozinMET409 Active (50mg) + Empagliflozin (10mg) |
| MET409P +Open-Label Empagliflozin | Placebo comparator | Drug: MET409 Placebo, Drug: EmpagliflozinMET409 Placebo (50mg) + Empagliflozin (10mg) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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 (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MET409 ActiveMET409 Active (50mg) | Drug | MET409 A, MET409A +Open-Label Empagliflozin |
| MET409 PlaceboMET409 Placebo (50mg) | Drug | MET409 P, MET409P +Open-Label Empagliflozin |
| EmpagliflozinEmpagliflozin (10mg) | Drug | MET409A +Open-Label Empagliflozin, MET409P +Open-Label Empagliflozin |
Primary outcome
Safety and tolerability of MET409 with or without empagliflozin (incidence of adverse events)
Time frame: 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.
6 secondary outcomes
Pharmacological activity of MET409 alone or in combination with empagliflozin
Time frame: 16 weeks
Pharmacokinetic profile of MET409 alone or in combination with empagliflozin
Time frame: 12 weeks
Pharmacokinetic profile of MET409 alone or in combination with empagliflozin
Time frame: 12 weeks
Pharmacokinetic profile of MET409 alone or in combination with empagliflozin
Time frame: 12 weeks
Pharmacodynamic profile of MET409 alone or in combination with empagliflozin
Time frame: 16 weeks
Pharmacodynamic profile of MET409 alone or in combination with empagliflozin
Time frame: 16 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2021.
- MetacrineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hubert C Chen, MD study chair
Metacrine, Inc.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MET409 Active and Empagliflozin in people with NASH and NASH - Nonalcoholic Steatohepatitis, run by Metacrine, Inc. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of MET409 with or without empagliflozin (incidence of adverse events) (time frame: Up to 28 days after last dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2021.