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

August 3, 2022 updated by: Akero Therapeutics, Inc

A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Efruxifermin in Subjects With 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.

Study Overview

Status

Completed

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

110

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • San Juan, Puerto Rico, 00927
        • Akero Clinical Study Site
    • Arizona
      • Tucson, Arizona, United States, 85711
        • Akero Clinical Study Site
    • Arkansas
      • Little Rock, Arkansas, United States, 72117
        • Akero Clinical Study Site
    • California
      • Huntington Park, California, United States, 90255
        • Akero Clinical Study Site
      • Los Angeles, California, United States, 90036
        • Akero Clinical Study Site
      • Los Angeles, California, United States, 90057
        • Akero Clinical Study Site
      • Panorama City, California, United States, 91402
        • Akero Clinical Study Site
      • Poway, California, United States, 92064
        • Akero Clinical Study Site
    • Florida
      • Boca Raton, Florida, United States, 33434
        • Akero Clinical Study Site
      • Lakewood Ranch, Florida, United States, 34211
        • Akero Clinical Study Site
      • Miami, Florida, United States, 33156
        • Akero Clinical Study Site
      • New Port Richey, Florida, United States, 34653
        • Akero Clinical Study Site
      • Ocoee, Florida, United States, 34761
        • Akero Clinical Study Site
      • Port Orange, Florida, United States, 32127
        • Akero Clinical Study Site
      • Sarasota, Florida, United States, 34240
        • Akero Clinical Study Site
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70809
        • Akero Clinical Study Site
      • Marrero, Louisiana, United States, 70072
        • Akero Clinical Study Site
    • Missouri
      • Kansas City, Missouri, United States, 64131
        • Akero Clinical Study Site
    • New Jersey
      • Berlin, New Jersey, United States, 08009
        • Akero Clinical Study Site
    • Tennessee
      • Chattanooga, Tennessee, United States, 37421
        • Akero Clinical Study Site
    • Texas
      • Cedar Park, Texas, United States, 78613
        • Akero Clinical Study Site
      • Dallas, Texas, United States, 75246
        • Akero Clinical Study Site
      • Edinburg, Texas, United States, 78539
        • Akero Clinical Study Site
      • Fort Worth, Texas, United States, 76104
        • Akero Clinical Study Site
      • San Antonio, Texas, United States, 78215
        • Akero Clinical Study Site
      • San Antonio, Texas, United States, 78229
        • Akero Clinical Study Site
      • Webster, Texas, United States, 77598
        • Akero Clinical Study Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: EFX Dose 1
Main Study
Administered by subcutaneous injection
EXPERIMENTAL: EFX Dose 2
Main Study
Administered by subcutaneous injection
EXPERIMENTAL: EFX Dose 3
Main Study
Administered by subcutaneous injection
PLACEBO_COMPARATOR: Placebo
Main Study
Administered by subcutaneous injection
EXPERIMENTAL: EFX Dose (Cohort C)
Administered by subcutaneous injection
PLACEBO_COMPARATOR: Placebo (Cohort C)
Administered by subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
22-24 weeks
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.
12 weeks
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.
22-24 weeks
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.
12 weeks
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.
22-24 weeks
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.
12, 16, and 20 weeks
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.
16 weeks
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.
12, 16, and 20 weeks
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.

12 and 16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 28, 2019

Primary Completion (ACTUAL)

February 10, 2021

Study Completion (ACTUAL)

January 10, 2022

Study Registration Dates

First Submitted

June 3, 2019

First Submitted That Met QC Criteria

June 4, 2019

First Posted (ACTUAL)

June 6, 2019

Study Record Updates

Last Update Posted (ACTUAL)

August 4, 2022

Last Update Submitted That Met QC Criteria

August 3, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Other Study ID Numbers

  • AK-US-001-0101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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