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

Phase 2

Completed

• Conditions: NASH - Nonalcoholic Steatohepatitis
• Interventions: Drug: Placebo; Drug: Efruxifermin

• Registration Number: NCT04767529
• Lead Sponsor: Akero Therapeutics, Inc

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-02-16
• Study First Submitted: 2021-02-16
• Study First Submitted QC: 2021-02-22
• Study First Posted: 2021-02-23
• Primary Completion: 2024-05-02
• Study Completion: 2024-05-02
• Results First Submitted: 2025-02-12
• Status Verified: 2025-04
• Results First Submitted QC: 2025-04-23
• Last Update Submitted: 2025-04-23
• Results First Posted: 2025-05-08
• Last Update Posted: 2025-05-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 128

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	double-blind, once-weekly subcutaneous injection
Efruxifermin 28 mg	Efruxifermin	double-blind, once-weekly subcutaneous injection
Efruxifermin 50 mg	Efruxifermin	double-blind, once-weekly subcutaneous injection

Primary Outcome Measures

Name	Time	Method
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)	24 Weeks	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

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in C-peptide at Week 24 and Week 96	24 Weeks, 96 Weeks	Change from baseline in C-peptide in EFX vs placebo groups
Change From Baseline in Adiponectin at Week 24 and Week 96	24 Weeks, 96 Weeks	Change from baseline in adiponectin in EFX vs placebo groups
Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage and no Worsening of Steatohepatitis at Week 96	96 Weeks	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
Proportion of Subjects Who Achieve Resolution of Steatohepatitis and no Worsening of Liver Fibrosis at Week 24 and Week 96	24 and 96 weeks	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)
Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage at Week 24 and Week 96	24 and 96 Weeks	Proportion of subjects in EFX vs placebo groups who achieve improvement in liver fibrosis (decrease ≥ 1 stage in NASH CRN fibrosis score)
Change From Baseline in Hepatic Fat Fraction in EFX vs Placebo Groups	24 and 96 Weeks	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
Change From Baseline in Lipoproteins at Week 24 and Week 96	24 and 96 weeks	Change from baseline of lipoproteins (triglycerides, Non-HDL-C, HDL-C and LDL-C) in EFX vs placebo groups
Change From Baseline of Hemoglobin A1c (Glycated Hemoglobin, HbA1c) at Week 24 and Week 96	24 Weeks, 96 Weeks	Change from baseline in hemoglobin A1c (glycated hemoglobin, HbA1c) in EFX vs placebo groups
Change From Baseline in Collagen III Neo-Peptide (C3M) at Week 24 and Week 96	24 and 96 Weeks	Change from Baseline in Collagen III Neo-Peptide (C3M) in EFX vs placebo groups
Change From Baseline in NIS4 Score at Week 24 and Week 96	24 and 96 Weeks	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
Change in Body Weight at Week 24 and Week 96	24 and 96 weeks	Change from baseline in body weight (kg) in EFX vs placebo groups
Change From Baseline in Liver Stiffness (kPa) at Week 24 and Week 96	24 and 96 weeks	Change from Baseline in Liver Stiffness Evaluated by FibroScan in EFX vs placebo groups at Week 24 and Week 96: Full Analysis Set
Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 24 and Week 96	24 Weeks, 96 Weeks	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
Change From Baseline in Enhanced Liver Fibrosis (ELF) Score at Week 24 and Week 96	24 and 96 Weeks	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
Change From Baseline in N-terminal Type III Collagen Propeptide (Pro-C3) at Week 24 and Week 96	24 and 96 Weeks	Change from Baseline in N-terminal Type III Collagen Propeptide (Pro-C3) in EFX vs placebo groups

Trial Locations

Locations (1)

Akero Clinical Study Site; 🇵🇷 San Juan, Puerto Rico