A Study of Efruxifermin in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH) (Symmetry)

June 23, 2026 updated by: Akero Therapeutics, Inc

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Efruxifermin in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH)

This is a multi-center evaluation of efruxifermin (EFX) in a randomized, double-blind, placebo-controlled study in cirrhotic subjects with biopsy-proven F4 compensated NASH.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
213

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
      • Mexico City, Mexico
        • Akero Clinical Study Site
      • Monterrey, Mexico
        • Akero Clinical Study Site
  • Puerto Rico
      • San Juan, Puerto Rico, 00927
        • Akero Clinical Study Site
  • United States
    • Arizona
      • Chandler, Arizona, United States, 85224
        • Akero Clinical Study Site
      • Glendale, Arizona, United States, 85306
        • Akero Clinical Study Site
      • Tucson, Arizona, United States, 85711
        • Akero Clinical Study Site
      • Tucson, Arizona, United States, 85712
        • Akero Clinical Study Site
    • Arkansas
      • North Little Rock, Arkansas, United States, 72117
        • Akero Clinical Study Site
    • California
      • Fresno, California, United States, 93720
        • Akero Clinical Study Site
      • Long Beach, California, United States, 90808
        • Akero Clinical Study Site
      • Los Angeles, California, United States, 90036
        • Akero Clinical Study Site
      • Pasadena, California, United States, 91105
        • Akero Clinical Study Site
    • Colorado
      • Englewood, Colorado, United States, 80113
        • Akero Clinical Study Site
    • Florida
      • Clearwater, Florida, United States, 33761
        • Akero Clinical Study Site
      • Fort Myers, Florida, United States, 33907
        • Akero Clinical Study Site
      • Fort Myers, Florida, United States, 33912
        • Akero Clinical Study Site
      • Hialeah Gardens, Florida, United States, 33016
        • Akero Clinical Study Site
      • Lakewood Rch, Florida, United States, 34211
        • Akero Clinical Study Site
      • Miami Lakes, Florida, United States, 33016
        • Akero Clinical Study Site
      • Ocala, Florida, United States, 34471
        • Akero Clinical Study Site
      • Sarasota, Florida, United States, 34240
        • Akero Clinical Study Site
    • Indiana
      • South Bend, Indiana, United States, 46635
        • Akero Clinical Study Site
    • Kansas
      • Topeka, Kansas, United States, 66606
        • Akero Clinical Study Site
    • Louisiana
      • Bastrop, Louisiana, United States, 71220
        • Akero Clinical Study Site
      • Marrero, Louisiana, United States, 70072
        • Akero Clinical Study Site
    • Nevada
      • Las Vegas, Nevada, United States, 89109
        • Akero Clinical Study Site
    • North Carolina
      • Concord, North Carolina, United States, 28027
        • Akero Clinical Study Site
      • Fayetteville, North Carolina, United States, 28304
        • Akero Clinical Study Site
      • Morehead City, North Carolina, United States, 28557
        • Akero Clinical Study Site
    • Ohio
      • Springboro, Ohio, United States, 45066
        • Akero Clinical Study Site
      • Westlake, Ohio, United States, 44145
        • Akero Clinical Study Site
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Akero Clinical Study Site
      • Greenwood, South Carolina, United States, 29646
        • Akero Clinical Study Site
      • Summerville, South Carolina, United States, 29485
        • Akero Clinical Study Site
    • Tennessee
      • Nashville, Tennessee, United States, 37211
        • Akero Clinical Study Site
    • Texas
      • Austin, Texas, United States, 78746
        • Akero Clinical Study Site
      • Dallas, Texas, United States, 75246
        • Akero Clinical Study Site
      • Edinburg, Texas, United States, 78504
        • Akero Clinical Study Site
      • Edinburg, Texas, United States, 78539
        • Akero Clinical Study Site
      • Fort Worth, Texas, United States, 75044
        • Akero Clinical Study Site
      • Fort Worth, Texas, United States, 76104
        • Akero Clinical Study Site
      • Houston, Texas, United States, 77030
        • Akero Clinical Study Site
      • Houston, Texas, United States, 77079
        • Akero Clinical Study Site
      • San Antonio, Texas, United States, 78215
        • Akero Clinical Study Site
      • Waco, Texas, United States, 76710
        • Akero Clinical Study Site
      • Webster, Texas, United States, 77598
        • Akero Clinical Study Site
      • Wichita Falls, Texas, United States, 76301
        • Akero Clinical Study Site
    • Utah
      • Ogden, Utah, United States, 84405
        • Akero Clinical Study Site
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Akero Clinical Study Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Males and non-pregnant, non-lactating females between 18-75 years of age inclusive, based on the date of signing informed consent.
  • Main Study Only: Previous history or presence of Type 2 diabetes or 2 out of 4 components of metabolic syndrome (obesity, dyslipidemia, elevated blood pressure, elevated fasting glucose).
  • Main Study Only: Biopsy-proven compensated cirrhosis due to NASH.
  • Cohort D Only: Diagnosis of type 2 diabetes
  • Cohort D Only: Use of GLP-1R agonist for at least 90 days
  • Cohort D Only: Biopsy-proven liver fibrosis stages 1, 2, or 3

Exclusion Criteria:

  • Main Study Only: Weight loss > 10% in the 90 days prior to screening until randomization or from the time of collection of the liver biopsy used to assess subject eligibility until randomization, whichever is longer.
  • Type 1 diabetes or uncontrolled Type 2 diabetes
  • Cohort D Only: Weight loss > 5% in the 90 days prior to screening
  • Cohort D Only: Presence of cirrhosis on liver biopsy

Other inclusion and exclusion criteria may apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo (Main Study)
Drug: Placebo
Placebo
Experimental: EFX 28 mg (Main Study)
Drug: EFX
Investigational drug, Efruxifermin
Experimental: EFX 50 mg (Main Study)
Drug: EFX
Investigational drug, Efruxifermin
Experimental: EFX 50 mg (Cohort D)
Drug: EFX
Investigational drug, Efruxifermin
Placebo Comparator: Placebo (Cohort D)
Drug: Placebo
Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Main: Change From Baseline in Fibrosis With no Worsening Steatohepatitis Assessed by NASH CRN System
Time Frame: Week 36
Proportion of subjects who achieve ≥ 1 stage improvement in fibrosis (based on NASH CRN fibrosis score) and no worsening of steatohepatitis at Week 36. No worsening of steatohepatitis was defined as no increase in score for any of the 3 components of NAS. The evaluation of the NAS endpoint was calculated using the following 3 categorical features: steatosis [0-3], lobular inflammation [0-3], and hepatocellular ballooning [0-2]. NAS was derived as the unweighted sum of steatosis, lobular inflammation, and hepatocellular ballooning scores.
Week 36

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Main: Resolution of NASH Assessed by the NASH CRN System
Time Frame: Week 36, Week 96
Proportion of subjects who achieve NASH resolution (defined as a NAS of 0-1 for inflammation and 0 for ballooning) as determined by the NASH CRN criteria at Week 36 and Week 96.
Week 36, Week 96
Main: Fibrosis Improvement and Resolution of NASH Assessed by the NASH CRN System
Time Frame: Week 36, Week 96
Proportion of subjects who achieve NASH resolution (defined as a NAS of 0-1 for inflammation and 0 for ballooning) and ≥ 1 stage improvement in fibrosis (based on NASH CRN fibrosis score) at Week 36 and Week 96
Week 36, Week 96
Main: Change From Baseline in Fibrosis With no Worsening of Steatohepatitis Assessed by the NASH CRN System
Time Frame: Week 96
Proportion of subjects who achieve ≥ 1 stage improvement in fibrosis (based on NASH CRN fibrosis score) and no worsening of steatohepatitis at Week 96
Week 96
Main: Change From Baseline in Fibrosis by NASH CRN System
Time Frame: Week 36, Week 96
Proportion of subjects who achieve ≥ 1 stage improvement in fibrosis (based on NASH CRN fibrosis score) at Week 36 and Week 96
Week 36, Week 96
Main: Change From Baseline in S-Pro-C3
Time Frame: Week 36, Week 48, Week 72, Week 96
Change from baseline in Serum Pro-C3 (N-terminal type III collagen propeptide), a biomarker of type III collagen formation reflecting fibrogenesis, measured in ug/L.
Week 36, Week 48, Week 72, Week 96
Main: Change From Baseline in Enhanced Liver Fibrosis (ELF) Score
Time Frame: Week 36, Week 48, Week 72, Week 96
ELF score is a composite serum biomarker score derived from HA, PIIINP, and TIMP-1 concentrations. Scores range approximately from 6 to 16, with higher scores indicating greater liver fibrosis severity.
Week 36, Week 48, Week 72, Week 96
Main: Change From Baseline in Liver Stiffness Assessed by Liver Elastography (kPa)
Time Frame: Week 36, Week 48, Week 72, Week 96
Change from baseline in liver stiffness assessed by liver elastography (kPa)
Week 36, Week 48, Week 72, Week 96
Main: Change From Baseline in Lipoproteins
Time Frame: Week 36, Week 48, Week 72, Week 96
Change from baseline in Triglycerides (mg/dL), total cholesterol (mg/dL), high-density lipoprotein (HDL-C) (mg/dL), non-HDL-C (mg/dL), and low-density lipoprotein (LDL-C) (mg/dL)
Week 36, Week 48, Week 72, Week 96
Main: Change From Baseline in HbA1c (%)
Time Frame: Week 36, Week 48, Week 72, Week 96
Glycated hemoglobin (HbA1c), expressed as a percentage, reflects average blood glucose levels over approximately 2 to 3 months and is used as a measure of glycemic control
Week 36, Week 48, Week 72, Week 96
Main: Change From Baseline in C-peptide (ug/L)
Time Frame: Week 36, Week 48, Week 72, Week 96
C-peptide reflects endogenous insulin secretion and pancreatic beta-cell function. Change from baseline represents the difference between the post-baseline value and the baseline measurement.
Week 36, Week 48, Week 72, Week 96
Main: Change From Baseline in Adiponectin (mg/L)
Time Frame: Week 36, Week 48, Week 72, Week 96
Adiponectin is involved in glucose and lipid metabolism and is used as a marker of metabolic status. Change from baseline represents the difference between the post-baseline value and the baseline measurement.
Week 36, Week 48, Week 72, Week 96
Main: Change From Baseline in Insulin (mIU/L)
Time Frame: Week 36, Week 48, Week 72, Week 96
Insulin reflects endogenous insulin levels measured after a period of fasting. Change from baseline represents the difference between the post-baseline value and the baseline measurement.
Week 36, Week 48, Week 72, Week 96
Main: Change From Baseline in HOMA-IR
Time Frame: Week 36, Week 48, Week 72, Week 96
HOMA-IR has no fixed upper limit. Values near 1 are typically observed in individuals with normal insulin sensitivity, while progressively higher values indicate increasing insulin resistance. The clinical significance of a given value may vary depending on the population and assay methodology. Change from baseline represents the difference between the post-baseline value and the baseline measurement.
Week 36, Week 48, Week 72, Week 96
Main: Change From Baseline in Body Weight
Time Frame: Week 36, Week 48, Week 96
Change from baseline in body weight (kg)
Week 36, Week 48, Week 96
Main: Number of Participants With ADA Against EFX
Time Frame: Through Week 96
Detect and measure ADA against EFX
Through Week 96
Main: To Assess the Safety and Tolerability of EFX
Time Frame: Through Week 96
Safety and tolerability will be assessed through the reporting of AEs, clinical laboratory tests, ECGs, ultrasounds, vital sign assessments, and concomitant medication usage
Through Week 96
Cohort D: To Assess the Safety and Tolerability of EFX Compared to Placebo When Added to an Existing GLP-1R Agonist in Subjects With Type 2 Diabetes and Liver Fibrosis Due to NASH
Time Frame: Through Week 12
Safety and tolerability will be assessed through the reporting of AEs, clinical laboratory assessments, ECGs, ultrasounds, vital sign assessments, and concomitant medication usage
Through Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Akero Therapeutics, Inc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 30, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 15, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 28, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 29, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 9, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 21, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 23, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AK-US-001-0103

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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