A Study of Efruxifermin in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH) (Symmetry)

Phase 2

Active, not recruiting

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

• Registration Number: NCT05039450
• 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 cirrhotic subjects with biopsy-proven F4 compensated NASH.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-07-29
• Study Start: 2021-07-30
• Study First Submitted QC: 2021-09-02
• Study First Posted: 2021-09-09
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-21
• Last Update Posted: 2023-04-25
• Primary Completion: 2023-10
• Study Completion: 2024-04

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Males and non-pregnant, non-lactating females between 18-75 years of age inclusive, based on the date of signing informed consent.
• Main Study Only: Previous history or presence of Type 2 diabetes or 2 out of 4 components of metabolic syndrome (obesity, dyslipidemia, elevated blood pressure, elevated fasting glucose).
• Main Study Only: Biopsy-proven compensated cirrhosis due to NASH.
• Cohort D Only: Diagnosis of type 2 diabetes
• Cohort D Only: Use of GLP-1R agonist for at least 90 days
• Cohort D Only: Biopsy-proven liver fibrosis stages 1, 2, or 3

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Exclusion Criteria

• Main Study Only: Weight loss > 10% in the 90 days prior to screening until randomization or from the time of collection of the liver biopsy used to assess subject eligibility until randomization, whichever is longer.
• Type 1 diabetes or uncontrolled Type 2 diabetes
• Cohort D Only: Weight loss > 5% in the 90 days prior to screening
• Cohort D Only: Presence of cirrhosis on liver biopsy

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 (Main Study)	EFX	-
EFX 50 mg (Cohort D)	EFX	-
Placebo (Cohort D)	Placebo	-
EFX 28 mg (Main Study)	EFX	-
Placebo (Main Study)	Placebo	-

Primary Outcome Measures

Name	Time	Method
Main: Change from baseline in fibrosis with no worsening steatohepatitis assessed by NASH CRN system	Week 36	Proportion of subjects who achieve ≥ 1 stage improvement in fibrosis (based on NASH CRN fibrosis score) and no worsening of steatohepatitis at Week 36.

Secondary Outcome Measures

Name	Time	Method
Main: Change from baseline in fibrosis in subjects with no worsening of steatohepatitis assessed by the NASH CRN system	Week 36, Week 96	Proportion of subjects who achieve ≥ 1 stage improvement in fibrosis (based on NASH CRN fibrosis score) at Week 36 and Week 96
Main: Resolution of NASH with no worsening of fibrosis assessed by the NASH CRN system	Week 36, Week 96	Proportion of subjects who achieve NASH resolution (defined as a NAS of 0-1 for inflammation and 0 for ballooning) as determined by the NASH CRN criteria at Week 36 and Week 96
Cohort D: To assess the safety and tolerability of EFX compared to placebo when added to an existing GLP-1R agonist in subjects with type 2 diabetes and liver fibrosis due to NASH	Through Week 12	Safety and tolerability will be assessed through the reporting of AEs, clinical laboratory assessments, ECGs, ultrasounds, vital sign assessments, and concomitant medication usage
Main: Change from baseline in non-invasive markers of fibrosis	Week 36, Week 48, Week 72, Week 96	Change from baseline in ELF score, Pro-C3 (ug/L),and liver stiffness assessed by liver elastography (kPa, CAP)
Main: Change from baseline in lipoproteins	Week 36, Week 48, Week 72, Week 96	Change from baseline in Triglycerides (mg/dL), total cholesterol (mg/dL), HDL-C (mg/dL), non-HDL-C (mg/dL), and LDL-C (mg/dL)
Main: Change from baseline of markers in insulin sensitivity and glycemic control	Week 36, Week 48, Week 72, Week 96	Change from baseline in HbA1c (%), C-peptide (ug/L), adiponectin (mg/L), insulin (mIU/L), and HOMA-IR
Main: Change from baseline in body weight	Week 36, Week 48, Week 96	Change from baseline in body weight (kg)
Main: To assess the immunogenicity of EFX	Through Week 96	Detect and measure ADA, including NAb, against EFX
Main: To assess the safety and tolerability of EFX	Through Week 96	Safety and tolerability will be assessed through the reporting of AEs, clinical laboratory tests, ECGs, ultrasounds, vital sign assessments, and concomitant medication usage

Trial Locations

Locations (1)

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