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

NASH - Nonalcoholic Steatohepatitis Clinical Trial

Official title:

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Efruxifermin in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05039450
• Other study ID #: AK-US-001-0103
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 30, 2021
• Est. completion date: April 2024

Study information

• Verified date: April 2023
• Source: Akero Therapeutics, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: April 2024
• Est. primary completion date: October 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Fatty Liver
• NASH - Nonalcoholic Steatohepatitis
• Non-alcoholic Fatty Liver Disease

Intervention

Drug:
• EFX
Investigational drug, Efruxifermin
• Placebo
Placebo

Locations

Country	Name	City	State
Mexico	Akero Clinical Study Site	Mexico City
Mexico	Akero Clinical Study Site	Monterrey
Puerto Rico	Akero Clinical Study Site	San Juan
United States	Akero Clinical Study Site	Austin	Texas
United States	Akero Clinical Study Site	Bastrop	Louisiana
United States	Akero Clinical Study Site	Chandler	Arizona
United States	Akero Clinical Study Site	Clearwater	Florida
United States	Akero Clinical Study Site	Concord	North Carolina
United States	Akero Clinical Study Site	Dallas	Texas
United States	Akero Clinical Study Site	Edinburg	Texas
United States	Akero Clinical Study Site	Edinburg	Texas
United States	Akero Clinical Study Site	Englewood	Colorado
United States	Akero Clinical Study Site	Fayetteville	North Carolina
United States	Akero Clinical Study Site	Fort Myers	Florida
United States	Akero Clinical Study Site	Fort Myers	Florida
United States	Akero Clinical Study Site	Fort Worth	Texas
United States	Akero Clinical Study Site	Fort Worth	Texas
United States	Akero Clinical Study Site	Fresno	California
United States	Akero Clinical Study Site	Glendale	Arizona
United States	Akero Clinical Study Site	Greenville	South Carolina
United States	Akero Clinical Study Site	Greenwood	South Carolina
United States	Akero Clinical Study Site	Hialeah Gardens	Florida
United States	Akero Clinical Study Site	Houston	Texas
United States	Akero Clinical Study Site	Houston	Texas
United States	Akero Clinical Study Site	Lakewood Ranch	Florida
United States	Akero Clinical Study Site	Las Vegas	Nevada
United States	Akero Clinical Study Site	Long Beach	California
United States	Akero Clinical Study Site	Los Angeles	California
United States	Akero Clinical Study Site	Marrero	Louisiana
United States	Akero Clinical Study Site	Miami Lakes	Florida
United States	Akero Clinical Study Site	Morehead City	North Carolina
United States	Akero Clinical Study Site	Nashville	Tennessee
United States	Akero Clinical Study Site	North Little Rock	Arkansas
United States	Akero Clinical Study Site	Ocala	Florida
United States	Akero Clinical Study Site	Ogden	Utah
United States	Akero Clinical Study Site	Pasadena	California
United States	Akero Clinical Study Site	Richmond	Virginia
United States	Akero Clinical Study Site	San Antonio	Texas
United States	Akero Clinical Study Site	Sarasota	Florida
United States	Akero Clinical Study Site	South Bend	Indiana
United States	Akero Clinical Study Site	Springboro	Ohio
United States	Akero Clinical Study Site	Summerville	South Carolina
United States	Akero Clinical Study Site	Topeka	Kansas
United States	Akero Clinical Study Site	Tucson	Arizona
United States	Akero Clinical Study Site	Tucson	Arizona
United States	Akero Clinical Study Site	Waco	Texas
United States	Akero Clinical Study Site	Webster	Texas
United States	Akero Clinical Study Site	Westlake	Ohio
United States	Akero Clinical Study Site	Wichita Falls	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Akero Therapeutics, Inc

Countries where clinical trial is conducted

United States,  Mexico,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Main: Change from baseline in fibrosis with no worsening steatohepatitis assessed by NASH CRN system	Proportion of subjects who achieve = 1 stage improvement in fibrosis (based on NASH CRN fibrosis score) and no worsening of steatohepatitis at Week 36.	Week 36
Secondary	Main: Resolution of NASH with no worsening of fibrosis assessed by the NASH CRN system	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	Week 36, Week 96
Secondary	Main: Change from baseline in fibrosis in subjects with no worsening of steatohepatitis assessed by the NASH CRN system	Proportion of subjects who achieve = 1 stage improvement in fibrosis (based on NASH CRN fibrosis score) and no worsening of steatohepatitis at Week 96	Week 96
Secondary	Main: Change from baseline in fibrosis in subjects with no worsening of steatohepatitis assessed by the NASH CRN system	Proportion of subjects who achieve = 1 stage improvement in fibrosis (based on NASH CRN fibrosis score) at Week 36 and Week 96	Week 36, Week 96
Secondary	Main: Change from baseline in non-invasive markers of fibrosis	Change from baseline in ELF score, Pro-C3 (ug/L),and liver stiffness assessed by liver elastography (kPa, CAP)	Week 36, Week 48, Week 72, Week 96
Secondary	Main: Change from baseline in lipoproteins	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)	Week 36, Week 48, Week 72, Week 96
Secondary	Main: Change from baseline of markers in insulin sensitivity and glycemic control	Change from baseline in HbA1c (%), C-peptide (ug/L), adiponectin (mg/L), insulin (mIU/L), and HOMA-IR	Week 36, Week 48, Week 72, Week 96
Secondary	Main: Change from baseline in body weight	Change from baseline in body weight (kg)	Week 36, Week 48, Week 96
Secondary	Main: To assess the immunogenicity of EFX	Detect and measure ADA, including NAb, against EFX	Through Week 96
Secondary	Main: To assess the safety and tolerability of EFX	Safety and tolerability will be assessed through the reporting of AEs, clinical laboratory tests, ECGs, ultrasounds, vital sign assessments, and concomitant medication usage	Through Week 96
Secondary	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	Safety and tolerability will be assessed through the reporting of AEs, clinical laboratory assessments, ECGs, ultrasounds, vital sign assessments, and concomitant medication usage	Through Week 12