A Study Evaluating Efruxifermin in Subjects With Non-Cirrhotic Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis

Phase 3

Recruiting

• Conditions: NASH With Fibrosis; MASH With Fibrosis
• Interventions: Drug: Efruxifermin; Drug: Placebo

• Registration Number: NCT06215716
• 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 subjects with non-cirrhotic NASH/MASH and fibrosis stage 2 or 3 (F2 or F3).

The study will enroll subjects in two cohorts for a total samples size of 1650 subjects.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-12-01
• Study First Submitted: 2023-12-06
• Study First Submitted QC: 2024-01-10
• Study First Posted: 2024-01-22
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-08
• Last Update Posted: 2025-01-09
• Primary Completion: 2032-11
• Study Completion: 2032-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1650

Inclusion Criteria

• Males and non-pregnant, non-lactating females between 18 - 80 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.

• Cohort 1: Biopsy-proven NASH/MASH. Must have had a liver biopsy obtained ≤ 180 days prior to screening with fibrosis stage 2 or 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).

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Exclusion Criteria

• Other causes of liver disease based on medical history and/or liver histology and/or central laboratory results.
• Presence of cirrhosis on liver biopsy (fibrosis stage 4).
• Type 1 or uncontrolled Type 2 diabetes.

Other inclusion and exclusion criteria may apply.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EFX 50 mg	Efruxifermin	-
Placebo	Placebo	-
EFX 28 mg	Efruxifermin	-

Primary Outcome Measures

Name	Time	Method
Cohort 1 Only: Resolution of NASH/MASH and a ≥ 1 stage improvement in fibrosis	52 Weeks	Based on NAS (scored by 0-1 for steatosis, 0-3 for inflammation, and 0-2 for ballooning) and NASH CRN fibrosis score (scored by a fibrosis score of 0-4, where 0 = no fibrosis, 1 = centrilobular pericellular fibrosis, 2 = centrilobular and periportal fibrosis, 3 = bridging fibrosis, 4 = cirrhosis)
Event-free survival	240 Weeks	Based on time from randomization to the first clinical event including evidence of disease progression, liver decompensation events, liver transplantation or eligibility for liver transplantation, and all-cause mortality.

Secondary Outcome Measures

Name	Time	Method
To assess the safety and tolerability of EFX through the reporting of abnormal clinical laboratory tests, ECGs, ultrasounds, vital sign assessments (number of patients)	52 Weeks, 240 Weeks
To assess the immunogenicity of EFX through the reporting of antidrug antibodies (number of patients)	52 Weeks, 240 Weeks
Change from baseline of markers of liver injury	52 Weeks, 240 Weeks	Uric acid (mg/dL)
To assess the safety and tolerability of EFX through the reporting of adverse events (frequency of events)	52 Weeks, 240 Weeks
Change from baseline of lipoproteins	52 Weeks, 240 Weeks	Total cholesterol (mg/dL), TG (mg/dL), Non-HDL-C (mg/dL), HDL-C (mg/dL), and LDL-C (mg/dL)
Change from baseline of markers of insulin sensitivity and glycemic control	52 Weeks, 240 Weeks	Adiponectin (mg/L)
Change from baseline of body weight (kg)	52 Weeks, 240 Weeks
To assess the safety and tolerability of EFX through the reporting of extent of exposure (weeks)	52 Weeks, 240 Weeks
Cohort 1 Only: ≥ 1 stage improvement in fibrosis and no worsening of steatohepatitis	52 Weeks	Based on NAS (scored by 0-1 for steatosis, 0-3 for inflammation, and 0-2 for ballooning) and NASH CRN fibrosis score (scored by a fibrosis score of 0-4, where 0 = no fibrosis, 1 = centrilobular pericellular fibrosis, 2 = centrilobular and periportal fibrosis, 3 = bridging fibrosis, 4 = cirrhosis)
To assess the safety and tolerability of EFX through the reporting of adverse events (severity of events)	52 Weeks, 240 Weeks
Cohort 1 Only: Resolution of NASH/MASH and no worsening of fibrosis	52 Weeks	Based on NAS (scored by 0-1 for steatosis, 0-3 for inflammation, and 0-2 for ballooning) and NASH CRN fibrosis score (scored by a fibrosis score of 0-4, where 0 = no fibrosis, 1 = centrilobular pericellular fibrosis, 2 = centrilobular and periportal fibrosis, 3 = bridging fibrosis, 4 = cirrhosis)
Change from baseline of non-invasive markers of liver fibrosis	52 Weeks, 240 Weeks	Liver stiffness assessed by transient elastography (FibroScan®) (kPa, CAP)

Trial Locations

Locations (1)

Akero Clinical Study Site; 🇬🇧 Newcastle-upon-Tyne, England, United Kingdom