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

• 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.

• 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	Drug: Placebo; Administered by subcutaneous injection
Experimental: EFX 28 mg	Drug: EFX; Administered by subcutaneous injection
Experimental: EFX 50 mg	Drug: EFX; Administered by subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in liver fibrosis with no worsening steatohepatitis assessed by NASH CRN system	24 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Resolution of steatohepatitis with no worsening of fibrosis assessed by the NASH CRN system	24 Weeks, 96 Weeks
Change from baseline in liver fibrosis with no worsening of steatohepatitis assessed by the NASH CRN system	96 Weeks
Responder based on NASH CRN: patients who had a decrease of ≥ one point in fibrosis score	24 Weeks, 96 Weeks
Change from baseline in hepatic fat fraction	24 Weeks, 96 Weeks
Change from baseline of lipoproteins - Non-HDL-C, HDL-C, and LDL-C	24 Weeks, 48 Weeks, 96 Weeks
Change from baseline of markers of glycemic control - HbA1c	24 Weeks, 48 Weeks, 96 Weeks
Change from baseline of markers of glycemic control - C-Peptide	24 Weeks, 48 Weeks, 96 Weeks
Change from baseline of markers of glycemic control - Adiponectin	24 Weeks, 48 Weeks, 96 Weeks
Change from baseline of markers of glycemic control - HOMA-IR	24 Weeks, 48 Weeks, 96 Weeks
Change from baseline of non-invasive fibrosis biomarkers - ELF	24 Weeks, 48 Weeks, 96 Weeks
Change from baseline of non-invasive fibrosis biomarkers - Pro-C3	24 Weeks, 48 Weeks, 96 Weeks
Change from baseline of non-invasive fibrosis biomarkers - NIS-4	24 Weeks, 48 Weeks, 96 Weeks
Change from baseline of non-invasive fibrosis biomarkers - liver stiffness assessed by transient elastography (FibroScan®)	24 Weeks, 48 Weeks, 96 Weeks
Change from baseline of body weight	24 Weeks, 48 Weeks, 96 Weeks

Collaborators and Investigators

• Sponsor: Akero Therapeutics, Inc

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2021
• Primary Completion (Actual): July 25, 2022
• Study Completion (Anticipated): May 1, 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): April 21, 2023
• Last Update Submitted That Met QC Criteria: April 20, 2023
• Last Verified: April 1, 2023

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