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

NASH - Nonalcoholic Steatohepatitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03976401
• Other study ID #: AK-US-001-0101
• Status: Completed
• Phase: Phase 2
• Start date: May 28, 2019
• Est. completion date: January 10, 2022

Study information

• Verified date: August 2022
• 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 administered for 16 weeks in subjects with biopsy proven F1 - F4 NASH.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: January 10, 2022
• Est. primary completion date: February 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Key Inclusion Criteria:

• Males and non-pregnant, non-lactating females between 18 - 80 years of age inclusive, based on the date of the screening visit.
• Main Study only: Body mass index (BMI) > 25 kg/m^2 (unless the patient has biopsy-proven NASH documented within the last 2 years).
• Main Study only: Must have confirmation of = 10% liver fat content on magnetic resonance imaging- proton density fat fraction (MRI-PDFF) at screening.
• Main Study only: Biopsy-proven NASH. Must have had a liver biopsy within 180 days of randomization with fibrosis stage 1 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)
• Cohort C only: FibroScan® measurement > 13.1 kPa.
• Cohort C only: Cirrhosis due to NASH. Liver biopsy consistent with F4 fibrosis according to the NAS system, confirmed by the central or local reader.

Exclusion Criteria:

• Weight gain or loss > 5% in the 3 months prior to randomization or > 10% in the 6 months prior to screening.
• Type 1 and insulin-dependent Type 2 diabetes.
• Poorly controlled hypertension (blood pressure > 160/100).

Related Conditions & MeSH terms

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

Intervention

Drug:
• EFX
Administered by subcutaneous injection
• Placebo
Administered by subcutaneous injection

Locations

Country	Name	City	State
Puerto Rico	Akero Clinical Study Site	San Juan
United States	Akero Clinical Study Site	Baton Rouge	Louisiana
United States	Akero Clinical Study Site	Berlin	New Jersey
United States	Akero Clinical Study Site	Boca Raton	Florida
United States	Akero Clinical Study Site	Cedar Park	Texas
United States	Akero Clinical Study Site	Chattanooga	Tennessee
United States	Akero Clinical Study Site	Dallas	Texas
United States	Akero Clinical Study Site	Edinburg	Texas
United States	Akero Clinical Study Site	Fort Worth	Texas
United States	Akero Clinical Study Site	Huntington Park	California
United States	Akero Clinical Study Site	Kansas City	Missouri
United States	Akero Clinical Study Site	Lakewood Ranch	Florida
United States	Akero Clinical Study Site	Little Rock	Arkansas
United States	Akero Clinical Study Site	Los Angeles	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	Florida
United States	Akero Clinical Study Site	New Port Richey	Florida
United States	Akero Clinical Study Site	Ocoee	Florida
United States	Akero Clinical Study Site	Panorama City	California
United States	Akero Clinical Study Site	Port Orange	Florida
United States	Akero Clinical Study Site	Poway	California
United States	Akero Clinical Study Site	San Antonio	Texas
United States	Akero Clinical Study Site	San Antonio	Texas
United States	Akero Clinical Study Site	Sarasota	Florida
United States	Akero Clinical Study Site	Tucson	Arizona
United States	Akero Clinical Study Site	Webster	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Akero Therapeutics, Inc

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Main: Absolute Change From Baseline in Hepatic Fat Fraction Assessed by MRI-PDFF at Week 12.	Main study. ANCOVA multiple imputation with treatment group and F1 fibrosis score (F1 vs F2-3) as factors and baseline hepatic fat fraction measured by MRI-PDFF as a covariate.	12 weeks
Secondary	Main: Absolute Change From Baseline in Hepatic Fat Fraction Assessed by MRI-PDFF at Week 22-24.	Main study. Included subjects with =30% relative fat reduction on MRI-PDFF at Week 12 that were required to return between Weeks 22 - 24. ANCOVA model with treatment group and F1 fibrosis score (F1 vs F2-3) as factors and baseline hepatic fat fraction as a covariate were performed.	22-24 weeks
Secondary	Main: Percent Change From Baseline in Hepatic Fat Fraction Measured by MRI-PDFF at Week 12.	Main study. ANCOVA multiple imputation with treatment group and F1 fibrosis score (F1 vs F2-3) as factors and baseline hepatic fat fraction measured by MRI-PDFF as a covariate.	12 weeks
Secondary	Main: Percent Change From Baseline in Hepatic Fat Fraction Measured by MRI-PDFF at Week 22-24.	Main study. ANCOVA multiple imputation with treatment group and F1 fibrosis score (F1 vs F2-3) as factors and baseline hepatic fat fraction measured by MRI-PDFF as a covariate.	22-24 weeks
Secondary	Main: Responder: Subjects Who Achieved a Clinically Meaningful Relative Reduction of at Least 30% in Liver Fat Content as Measured by MRI-PDFF at Week 12.	Main Study. The analyses included the treatment group and F1 fibrosis score (F1 vs F2-3) as factors and baseline hepatic fat fraction measured by MRI-PDFF as a covariate.	12 weeks
Secondary	Main: Responder Based on NAFLD Activity Score System (NAS): Subjects Who Had a Decrease of =2 Points in NAS With at Least a 1-point Reduction in Either Lobular Inflammation or Hepatocellular Ballooning and With no Concurrent Worsening of Fibrosis Stage.	Main study: Responders were defined for subjects with = 30% relative fat reduction on MRI-PDFF at Week 12 and required to return between Weeks 22 - 24. Fisher's exact test was used for the analysis using the Full Analysis Set with missing values imputed as non-responders and repeated on Liver Biopsy Evaluable Analysis Set without imputation.	22-24 weeks
Secondary	Main: Change From Baseline in ALT at Week 12, 16, and 20.	ANCOVA model with treatment group, baseline hepatic fat fraction (<15% vs =15%), and F1 fibrosis score (F1 vs F2-3) as factors and baseline value as a covariate.	12, 16, and 20 weeks
Secondary	Cohort C: Change From Baseline in Liver Stiffness as Evaluated by FibroScan at Week 16	Cohort C: ANCOVA model with treatment group as a factor and baseline liver stiffness as evaluated by FibroScan® as a covariate using the Full Analysis Set. Missing values at Week 16 were imputed using the last-observed-carried-forward (LOCF) method.	16 weeks
Secondary	Cohort C: Change From Baseline in Non-invasive Biomarkers Including Pro-C3 at Week 12, 16, and 20.	Cohort C. ANCOVA model with treatment group as a factor and baseline liver stiffness as evaluated by FibroScan® as a covariate using the Full Analysis Set. Missing values were imputed using the last-observed-carried-forward (LOCF) method.	12, 16, and 20 weeks
Secondary	Cohort C: Change From Baseline in Non-invasive Biomarkers Including Liver Fibrosis by ELF Test Score at Week 12 and 16.	Cohort C. The enhanced liver fibrosis (ELF) score describes the severity of liver fibrosis where a score of <7.7 indicates no or mild fibrosis, a score of =7.7 to <9.8 indicates moderate fibrosis, and a score of =9.8 indicates severe fibrosis. A change from baseline with a negative value indicates a decrease in severity of liver fibrosis.; An ANCOVA model with treatment group as a factor and baseline liver stiffness as evaluated by FibroScan® as a covariate using the Full Analysis Set was used. Missing values were imputed using the last-observed-carried-forward (LOCF) method.	12 and 16 weeks