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

Phase 2

Completed

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

• Registration Number: NCT03976401
• Lead Sponsor: Akero Therapeutics, Inc

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-05-28
• Study First Submitted: 2019-06-03
• Study First Submitted QC: 2019-06-04
• Study First Posted: 2019-06-06
• Primary Completion: 2021-02-10
• Study Completion: 2022-01-10
• Results First Submitted: 2022-06-06
• Status Verified: 2022-08
• Results First Submitted QC: 2022-08-03
• Last Update Submitted: 2022-08-03
• Results First Posted: 2022-08-04
• Last Update Posted: 2022-08-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 110

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.

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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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Main Study
EFX Dose (Cohort C)	EFX	-
Placebo (Cohort C)	Placebo	-
EFX Dose 1	EFX	Main Study
EFX Dose 2	EFX	Main Study
EFX Dose 3	EFX	Main Study

Primary Outcome Measures

Name	Time	Method
Main: Absolute Change From Baseline in Hepatic Fat Fraction Assessed by MRI-PDFF at Week 12.	12 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Main: Absolute Change From Baseline in Hepatic Fat Fraction Assessed by MRI-PDFF at Week 22-24.	22-24 weeks	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.
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.	22-24 weeks	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.
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.	12 weeks	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.
Cohort C: Change From Baseline in Liver Stiffness as Evaluated by FibroScan at Week 16	16 weeks	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.
Main: Percent Change From Baseline in Hepatic Fat Fraction Measured by MRI-PDFF at Week 12.	12 weeks	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.
Cohort C: Change From Baseline in Non-invasive Biomarkers Including Liver Fibrosis by ELF Test Score at Week 12 and 16.	12 and 16 weeks	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.
Main: Percent Change From Baseline in Hepatic Fat Fraction Measured by MRI-PDFF at Week 22-24.	22-24 weeks	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.
Main: Change From Baseline in ALT at Week 12, 16, and 20.	12, 16, and 20 weeks	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.
Cohort C: Change From Baseline in Non-invasive Biomarkers Including Pro-C3 at Week 12, 16, and 20.	12, 16, and 20 weeks	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.

Trial Locations

Locations (1)

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