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Completed

NCT Number: NCT03976401

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

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.

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Key information

Conditions

NASH - Nonalcoholic Steatohepatitis Digestive System Diseases Fatty Liver Liver Diseases Non-alcoholic Fatty Liver Disease

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Akero Clinical Study Site, San Juan, Puerto Rico

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

EFX

Drug

Administered by subcutaneous injection

Placebo

Drug

Administered by subcutaneous injection

Primary outcomes

  1. Main: Absolute Change From Baseline in Hepatic Fat Fraction Assessed by MRI-PDFF at Week 12.

    Time frame: 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 outcomes

  1. Main: Absolute Change From Baseline in Hepatic Fat Fraction Assessed by MRI-PDFF at Week 22-24.

    Time frame: 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.

  2. Main: Percent Change From Baseline in Hepatic Fat Fraction Measured by MRI-PDFF at Week 12.

    Time frame: 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.

  3. Main: Percent Change From Baseline in Hepatic Fat Fraction Measured by MRI-PDFF at Week 22-24.

    Time frame: 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.

  4. 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.

    Time frame: 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.

  5. 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.

    Time frame: 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.

  6. Main: Change From Baseline in ALT at Week 12, 16, and 20.

    Time frame: 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.

  7. Cohort C: Change From Baseline in Liver Stiffness as Evaluated by FibroScan at Week 16

    Time frame: 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.

  8. Cohort C: Change From Baseline in Non-invasive Biomarkers Including Pro-C3 at Week 12, 16, and 20.

    Time frame: 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.

  9. Cohort C: Change From Baseline in Non-invasive Biomarkers Including Liver Fibrosis by ELF Test Score at Week 12 and 16.

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Akero Therapeutics, Inc

Industry

Registry information

Official study title

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

Important dates

Study start
2019
Primary completion
2021
Study completion
2022
First posted
Jun 6, 2019
Registry last updated
Aug 4, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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