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

NCT04767529 | Completed Phase 2 Results FDA Drug

• 1 other identifier: AK-US-001-0102
• Study Type: interventional
• Target: 128
• Locations: 2 countries
• Sites: 55

Brief Summary

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.

Conditions

NASH - Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

• Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage and no Worsening of Steatohepatitis 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

  24 and 96 weeks

• Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage at Week 24 and Week 96

  24 and 96 Weeks

• Change From Baseline in Hepatic Fat Fraction in EFX vs Placebo Groups

  24 and 96 Weeks

• Change From Baseline in Lipoproteins at Week 24 and Week 96

  24 and 96 weeks

Study Arms (3)

placebo

PLACEBO COMPARATOR

double-blind, once-weekly subcutaneous injection

Drug: Placebo

Efruxifermin 28 mg

EXPERIMENTAL

double-blind, once-weekly subcutaneous injection

Drug: Efruxifermin

Efruxifermin 50 mg

PLACEBO COMPARATOR

double-blind, once-weekly subcutaneous injection

Drug: Efruxifermin

Interventions

Efruxifermin DRUG

subcutaneous injection

Also known as: EFX

Efruxifermin 28 mg; Efruxifermin 50 mg

Placebo DRUG

subcutaneous injection

placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Akero Therapeutics, Inc: lead

Study Sites (55)

Akero Clinical Study Site

Chandler, Arizona, 85224, United States

Location

Akero Clinical Study Site

Glendale, Arizona, 85304, United States

Location

Akero Clinical Study Site

Tucson, Arizona, 85712, United States

Location

Akero Clinical Study Site

North Little Rock, Arkansas, 72117, United States

Location

Akero Clinical Study Site

Chula Vista, California, 91910, United States

Location

Akero Clinical Study Site

Fresno, California, 93720, United States

Location

Akero Clinical Study Site

La Jolla, California, 92037, United States

Location

Akero Clinical Study Site

Los Angeles, California, 90036, United States

Location

Akero Clinical Study Site

Los Angeles, California, 90048, United States

Location

Akero Clinical Study Site

Los Angeles, California, 90057, United States

Location

Akero Clinical Study Site

Orange, California, 92866, United States

Location

Akero Clinical Study Site

Panorama City, California, 91402, United States

Location

Akero Clinical Study Site

Rialto, California, 92866, United States

Location

Akero Clinical Study Site

Santa Ana, California, 92704, United States

Location

Akero Clinical Study Site

Fort Myers, Florida, 33912, United States

Location

Akero Clinical Study Site

Inverness, Florida, 34452, United States

Location

Akero Clinical Study Site

Lakewood Rch, Florida, 34211, United States

Location

Akero Clinical Study Site

Miami, Florida, 33134, United States

Location

Akero Clinical Study Site

Miami, Florida, 33147, United States

Location

Akero Clinical Study Site

Miami Lakes, Florida, 33016, United States

Location

Akero Clinical Study Site

Ocala, Florida, 34471, United States

Location

Akero Clinical Study Site

Sarasota, Florida, 94240, United States

Location

Akero Clinical Study Site

Marietta, Georgia, 30060, United States

Location

Akero Clinical Study Site

Topeka, Kansas, 66606, United States

Location

Akero Clinical Study Site

Baton Rouge, Louisiana, 70809, United States

Location

Akero Clinical Study Site

Marrero, Louisiana, 70072, United States

Location

Akero Clinical Study Site

Ypsilanti, Michigan, 48197, United States

Location

Akero Clinical Study Site

Flowood, Mississippi, 39232, United States

Location

Akero Clinical Study Site

Jackson, Mississippi, 39216, United States

Location

Akero Clinical Study Site

Las Vegas, Nevada, 89106, United States

Location

Akero Clinical Study Site

Charlotte, North Carolina, 28204, United States

Location

Akero Clinical Study Site

Durham, North Carolina, 27712, United States

Location

Akero Clinical Study Site

Morehead City, North Carolina, 28557, United States

Location

Akero Clinical Study Site

Cincinnati, Ohio, 45219, United States

Location

Akero Clinical Study Site

Greenville, South Carolina, 29605, United States

Location

Akero Clinical Study Site

Hermitage, Tennessee, 37076, United States

Location

Akero Clinical Study Site

Nashville, Tennessee, 37211, United States

Location

Akero Clinical Study Site

Arlington, Texas, 76012, United States

Location

Akero Clinical Study Site

Austin, Texas, 78757, United States

Location

Akero Clinical Study Site

Cedar Park, Texas, 75246, United States

Location

Akero Clinical Study Site

Dallas, Texas, 75234, United States

Location

Akero Clinical Study Site

Dallas, Texas, 75246, United States

Location

Akero Clinical Study Site

Edinburg, Texas, 78539, United States

Location

Akero Clinical Study Site

Fort Worth, Texas, 76104, United States

Location

Akero Clinical Study Site

Garland, Texas, 75044, United States

Location

Akero Clinical Study Site

Houston, Texas, 77058, United States

Location

Akero Clinical Study Site

San Antonio, Texas, 78209, United States

Location

Akero Clinical Study Site

San Antonio, Texas, 78215, United States

Location

Akero Clinical Study Site

San Antonio, Texas, 78229, United States

Location

Akero Clinical Study Site

San Marcos, Texas, 78666, United States

Location

Akero Clinical Study Site

Webster, Texas, 77598, United States

Location

Akero Clinical Study Site

Charlottesville, Virginia, 22908, United States

Location

Akero Clinical Study Site

Richmond, Virginia, 23249, United States

Location

Akero Clinical Study Site

Richmond, Virginia, 23298, United States

Location

Akero Clinical Study Site

San Juan, 927, Puerto Rico

Location

Related Publications (2)

• 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.

  PMID: 37802088 BACKGROUND

• Noureddin M, Frias JP, Neff GW, Lucas KJ, Behling C, Bedossa P, Dubourg J, Chan D, Burch M, Fong E, de Temple B, Minerva M, Barrett K, Shringarpure R, Tillman EJ, Rolph T, Cheng A, Yale K. Safety and efficacy of once-weekly efruxifermin versus placebo in metabolic dysfunction-associated steatohepatitis (HARMONY): 96-week results from a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet. 2025 Aug 16;406(10504):719-730. doi: 10.1016/S0140-6736(25)01073-6.

  PMID: 40818852 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Kitty Yale
• Organization: Akero Therapeutics, Inc.

harmonystudies@akerotx.com

(650) 487-6488

Study Officials

• Akero Study Director

  Study Director

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2021
• First Posted: February 23, 2021
• Study Start: February 16, 2021
• Primary Completion: May 2, 2024
• Study Completion: May 2, 2024
• Last Updated: June 18, 2025
• Results First Posted: May 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

PR (1); US (54)