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

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: Active, not recruiting
• Conditions: NASH - Nonalcoholic Steatohepatitis
• Intervention / Treatment: Drug: Placebo; Drug: EFX

• Study Type: Interventional
• Enrollment (Actual): 182
• Phase: Phase 2

Contacts and Locations

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 Ranch, 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

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
Main: Change from baseline in fibrosis with no worsening steatohepatitis assessed by NASH CRN system	Proportion of subjects who achieve ≥ 1 stage improvement in fibrosis (based on NASH CRN fibrosis score) and no worsening of steatohepatitis at Week 36.	Week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Main: Change from baseline in fibrosis in subjects with no worsening of steatohepatitis assessed by the NASH CRN system	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 in subjects with no worsening of steatohepatitis assessed by the NASH CRN system	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 non-invasive markers of fibrosis	Change from baseline in ELF score, Pro-C3 (ug/L),and liver stiffness assessed by liver elastography (kPa, CAP)	Week 36, Week 48, Week 72, Week 96
Main: Change from baseline in lipoproteins	Change from baseline in Triglycerides (mg/dL), total cholesterol (mg/dL), HDL-C (mg/dL), non-HDL-C (mg/dL), and LDL-C (mg/dL)	Week 36, Week 48, Week 72, Week 96
Main: Change from baseline of markers in insulin sensitivity and glycemic control	Change from baseline in HbA1c (%), C-peptide (ug/L), adiponectin (mg/L), insulin (mIU/L), and HOMA-IR	Week 36, Week 48, Week 72, Week 96
Main: Change from baseline in body weight	Change from baseline in body weight (kg)	Week 36, Week 48, Week 96
Main: To assess the immunogenicity of EFX	Detect and measure ADA, including NAb, against EFX	Through Week 96
Main: To assess the safety and tolerability of EFX	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	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
Main: Resolution of NASH assessed by the NASH CRN system	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 with no worsening of NASH assessed by the NASH CRN system	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

Collaborators and Investigators

• Sponsor: Akero Therapeutics, Inc

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2021
• Primary Completion (Actual): August 25, 2023
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: July 29, 2021
• First Submitted That Met QC Criteria: September 2, 2021
• First Posted (Actual): September 9, 2021

Study Record Updates

• Last Update Posted (Actual): April 9, 2025
• Last Update Submitted That Met QC Criteria: April 7, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID 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