A Study of Efruxifermin in Non-Cirrhotic Subjects With Histologically Confirmed Nonalcoholic Steatohepatitis (NASH) (Harmony)

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

This is a multi-center evaluation of efruxifermin (EFX) in a randomized, double-blind, placebo-controlled study in non-cirrhotic subjects with biopsy-proven F2 - F3 NASH.

Study Overview

• Status: Completed
• Conditions: NASH - Nonalcoholic Steatohepatitis
• Intervention / Treatment: Drug: Placebo; Drug: Efruxifermin

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 927
    • Akero Clinical Study Site
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Akero Clinical Study Site
    • Glendale, Arizona, United States, 85304
      • 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
    • Chula Vista, California, United States, 91910
      • Akero Clinical Study Site
    • Fresno, California, United States, 93720
      • Akero Clinical Study Site
    • La Jolla, California, United States, 92037
      • Akero Clinical Study Site
    • Los Angeles, California, United States, 90036
      • Akero Clinical Study Site
    • Los Angeles, California, United States, 90057
      • Akero Clinical Study Site
    • Los Angeles, California, United States, 90048
      • Akero Clinical Study Site
    • Orange, California, United States, 92866
      • Akero Clinical Study Site
    • Panorama City, California, United States, 91402
      • Akero Clinical Study Site
    • Rialto, California, United States, 92866
      • Akero Clinical Study Site
    • Santa Ana, California, United States, 92704
      • Akero Clinical Study Site
  • Florida
    • Fort Myers, Florida, United States, 33912
      • Akero Clinical Study Site
    • Inverness, Florida, United States, 34452
      • Akero Clinical Study Site
    • Lakewood Ranch, Florida, United States, 34211
      • Akero Clinical Study Site
    • Miami, Florida, United States, 33134
      • Akero Clinical Study Site
    • Miami, Florida, United States, 33147
      • 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, 94240
      • Akero Clinical Study Site
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Akero Clinical Study Site
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Akero Clinical Study Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Akero Clinical Study Site
    • Marrero, Louisiana, United States, 70072
      • Akero Clinical Study Site
  • Michigan
    • Ypsilanti, Michigan, United States, 48197
      • Akero Clinical Study Site
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Akero Clinical Study Site
    • Jackson, Mississippi, United States, 39216
      • Akero Clinical Study Site
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Akero Clinical Study Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Akero Clinical Study Site
    • Durham, North Carolina, United States, 27712
      • Akero Clinical Study Site
    • Morehead City, North Carolina, United States, 28557
      • Akero Clinical Study Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Akero Clinical Study Site
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Akero Clinical Study Site
  • Tennessee
    • Hermitage, Tennessee, United States, 37076
      • Akero Clinical Study Site
    • Nashville, Tennessee, United States, 37211
      • Akero Clinical Study Site
  • Texas
    • Arlington, Texas, United States, 76012
      • Akero Clinical Study Site
    • Austin, Texas, United States, 78757
      • Akero Clinical Study Site
    • Cedar Park, Texas, United States, 75246
      • Akero Clinical Study Site
    • Dallas, Texas, United States, 75246
      • Akero Clinical Study Site
    • Dallas, Texas, United States, 75234
      • Akero Clinical Study Site
    • Edinburg, Texas, United States, 78539
      • Akero Clinical Study Site
    • Fort Worth, Texas, United States, 76104
      • Akero Clinical Study Site
    • Garland, Texas, United States, 75044
      • Akero Clinical Study Site
    • Houston, Texas, United States, 77058
      • Akero Clinical Study Site
    • San Antonio, Texas, United States, 78215
      • Akero Clinical Study Site
    • San Antonio, Texas, United States, 78229
      • Akero Clinical Study Site
    • San Antonio, Texas, United States, 78209
      • Akero Clinical Study Site
    • San Marcos, Texas, United States, 78666
      • Akero Clinical Study Site
    • Webster, Texas, United States, 77598
      • Akero Clinical Study Site
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Akero Clinical Study Site
    • Richmond, Virginia, United States, 23298
      • Akero Clinical Study Site
    • Richmond, Virginia, United States, 23249
      • 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 the screening visit.
• Previous history or presence of 2 out of 4 components of metabolic syndrome (obesity, dyslipidemia, elevated blood pressure, elevated fasting glucose) or type 2 diabetes.
• FibroScan measurement > 8.5 kPa [kilopascal].

• Biopsy-proven NASH. Must have had a liver biopsy obtained ≤ 180 days prior to randomization with fibrosis stage 2 to 3 and a non-alcoholic fatty liver disease (NAFLD) activity score (NAS) of ≥ 4 with at least a score of 1 in each of the following NAS components:

  • Steatosis (scored 0 to 3),
  • Ballooning degeneration (scored 0 to 2), and
  • Lobular inflammation (scored 0 to 3).

Exclusion Criteria:

• Weight loss > 5% in the 3 months prior to screening until randomization or from the time of the diagnostic liver biopsy until randomization, whichever is longer.
• Presence of cirrhosis on liver biopsy (stage 4 fibrosis).
• Type 1 or uncontrolled Type 2 diabetes.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; double-blind, once-weekly subcutaneous injection	Drug: Placebo; subcutaneous injection
Experimental: Efruxifermin 28 mg; double-blind, once-weekly subcutaneous injection	Drug: Efruxifermin; subcutaneous injection; Other Names: EFX
Placebo Comparator: Efruxifermin 50 mg; double-blind, once-weekly subcutaneous injection	Drug: Efruxifermin; subcutaneous injection; Other Names: EFX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Efruxifermin (EFX) vs Placebo on Fibrosis Regression in Participants With Metabolic Dysfunction-associated Steatohepatitis (MASH)-Associated Stage 2 or 3 Fibrosis (F2 or F3)	Proportions of subjects in EFX vs placebo groups with improvement in liver fibrosis, defined as ≥ 1 stage NASH Clinical Research Network [CRN] fibrosis score (score ranges from 0 to 4, increasing with fibrosis severity), and no worsening of steatohepatitis (no increase in NASH Activity Score [NAS], which ranges from 0 to 8 and is the sum of scores of steatosis, lobular inflammation, and hepatocyte ballooning), at Week 24	24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage and no Worsening of Steatohepatitis at Week 96	Proportions of subjects in EFX vs baseline groups who achieve improvement in liver fibrosis (decrease of ≥ 1 stage in NASH CRN fibrosis score) and no worsening of steatohepatitis (no increase in NAS for ballooning, inflammation, or steatosis) at Week 96	96 Weeks
Proportion of Subjects Who Achieve Resolution of Steatohepatitis and no Worsening of Liver Fibrosis at Week 24 and Week 96	Proportions of subjects in EFX vs placebo groups who achieve resolution of steatohepatitis (defined as a NAS of 0-1 for inflammation, 0 for ballooning, and any value for steatosis) and no worsening of liver fibrosis (determined by the NASH CRN criteria)	24 and 96 weeks
Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage at Week 24 and Week 96	Proportion of subjects in EFX vs placebo groups who achieve improvement in liver fibrosis (decrease ≥ 1 stage in NASH CRN fibrosis score)	24 and 96 Weeks
Change From Baseline in Hepatic Fat Fraction in EFX vs Placebo Groups	Change from baseline in hepatic fat fraction, measured by magnetic resonance imaging proton-density fat fraction (MRI-PDFF): Week 24 and Week 96 MRI-PDFF Analysis Set	24 and 96 Weeks
Change From Baseline in Lipoproteins at Week 24 and Week 96	Change from baseline of lipoproteins (triglycerides, Non-HDL-C, HDL-C and LDL-C) in EFX vs placebo groups	24 and 96 weeks
Change From Baseline of Hemoglobin A1c (Glycated Hemoglobin, HbA1c) at Week 24 and Week 96	Change from baseline in hemoglobin A1c (glycated hemoglobin, HbA1c) in EFX vs placebo groups	24 Weeks, 96 Weeks
Change From Baseline in C-peptide at Week 24 and Week 96	Change from baseline in C-peptide in EFX vs placebo groups	24 Weeks, 96 Weeks
Change From Baseline in Adiponectin at Week 24 and Week 96	Change from baseline in adiponectin in EFX vs placebo groups	24 Weeks, 96 Weeks
Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 24 and Week 96	Change from baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in EFX vs placebo groups The Homeostatic Model Assessment of Insulin Resistance, HOMA-IR, is a calculated index that estimates insulin resistance based on fasting glucose and insulin levels. Higher values indicate greater insulin resistance. < 1.0: Normal insulin sensitivity 1.0-1.9: Mild insulin resistance 2.0-2.9: Moderate insulin resistance > 2.9: Severe insulin resistance	24 Weeks, 96 Weeks
Change From Baseline in Enhanced Liver Fibrosis (ELF) Score at Week 24 and Week 96	Change from Baseline in Enhanced Liver Fibrosis (ELF) Score in EFX vs placebo groups The Enhanced Liver Fibrosis (ELF) score is a non-invasive blood test that assesses the risk of liver fibrosis and its progression. Lower risk (<9.8): Suggests a lower risk of advanced liver fibrosis. Mid risk (9.8-11.2): Indicates a moderate risk of disease progression. Higher risk (≥11.3): Suggests a higher risk of developing cirrhosis or liver-related events	24 and 96 Weeks
Change From Baseline in N-terminal Type III Collagen Propeptide (Pro-C3) at Week 24 and Week 96	Change from Baseline in N-terminal Type III Collagen Propeptide (Pro-C3) in EFX vs placebo groups	24 and 96 Weeks
Change From Baseline in Collagen III Neo-Peptide (C3M) at Week 24 and Week 96	Change from Baseline in Collagen III Neo-Peptide (C3M) in EFX vs placebo groups	24 and 96 Weeks
Change From Baseline in NIS4 Score at Week 24 and Week 96	Change from Baseline in NIS4 score in EFX vs placebo groups NIS4 scores range from 0 to 1 and are calculated by combining the results of four individual biomarker assays [miR34a-5p, α2-macroglobulin (A2M), YKL-40 and HbA1c] each of which contributes to the test's ability to detect liver inflammation and/or fibrosis. >0.63: Higher risk of NASH or advanced fibrosis 0.37-0.63: Moderate risk, and additional testing may be considered <0.36: Lower risk of of NASH or advanced fibrosis	24 and 96 Weeks
Change in Body Weight at Week 24 and Week 96	Change from baseline in body weight (kg) in EFX vs placebo groups	24 and 96 weeks
Change From Baseline in Liver Stiffness (kPa) at Week 24 and Week 96	Change from Baseline in Liver Stiffness Evaluated by FibroScan in EFX vs placebo groups at Week 24 and Week 96: Full Analysis Set	24 and 96 weeks

Collaborators and Investigators

• Sponsor: Akero Therapeutics, Inc
• Investigators: Study Director: Akero Study Director, Study Director

Publications and helpful links

General Publications

• Harrison SA, Frias JP, Neff G, Abrams GA, Lucas KJ, Sanchez W, Gogia S, Sheikh MY, Behling C, Bedossa P, Shao L, Chan D, Fong E, de Temple B, Shringarpure R, Tillman EJ, Rolph T, Cheng A, Yale K; HARMONY Study Group. Safety and efficacy of once-weekly efruxifermin versus placebo in non-alcoholic steatohepatitis (HARMONY): a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Gastroenterol Hepatol. 2023 Dec;8(12):1080-1093. doi: 10.1016/S2468-1253(23)00272-8. Epub 2023 Oct 3.

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2021
• Primary Completion (Actual): May 2, 2024
• Study Completion (Actual): May 2, 2024

Study Registration Dates

• First Submitted: February 16, 2021
• First Submitted That Met QC Criteria: February 22, 2021
• First Posted (Actual): February 23, 2021

Study Record Updates

• Last Update Posted (Actual): June 18, 2025
• Last Update Submitted That Met QC Criteria: June 2, 2025
• Last Verified: June 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-001-0102

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