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

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ClinicalTrials.gov Identifier: NCT03976401
Recruitment Status : Completed
First Posted : June 6, 2019
Results First Posted : August 4, 2022
Last Update Posted : August 4, 2022
Sponsor:
Information provided by (Responsible Party):
Akero Therapeutics, Inc

Study Description
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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.

Condition or disease Intervention/treatment Phase
NASH - Nonalcoholic Steatohepatitis Drug: EFX Drug: Placebo Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Efruxifermin in Subjects With Nonalcoholic Steatohepatitis (NASH)
Actual Study Start Date : May 28, 2019
Actual Primary Completion Date : February 10, 2021
Actual Study Completion Date : January 10, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: EFX Dose 1
Main Study
 Drug: EFX
Administered by subcutaneous injection
Experimental: EFX Dose 2
Main Study
 Drug: EFX
Administered by subcutaneous injection
Experimental: EFX Dose 3
Main Study
 Drug: EFX
Administered by subcutaneous injection
Placebo Comparator: Placebo
Main Study
 Drug: Placebo
Administered by subcutaneous injection
Experimental: EFX Dose (Cohort C) Drug: EFX
Administered by subcutaneous injection
Placebo Comparator: Placebo (Cohort C) Drug: Placebo
Administered by subcutaneous injection


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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.



Eligibility Criteria
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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03976401


Locations
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United States, Arizona
Akero Clinical Study Site
Tucson, Arizona, United States, 85711
United States, Arkansas
Akero Clinical Study Site
Little Rock, Arkansas, United States, 72117
United States, California
Akero Clinical Study Site
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
United States, Florida
Akero Clinical Study Site
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
United States, Louisiana
Akero Clinical Study Site
Baton Rouge, Louisiana, United States, 70809
Akero Clinical Study Site
Marrero, Louisiana, United States, 70072
United States, Missouri
Akero Clinical Study Site
Kansas City, Missouri, United States, 64131
United States, New Jersey
Akero Clinical Study Site
Berlin, New Jersey, United States, 08009
United States, Tennessee
Akero Clinical Study Site
Chattanooga, Tennessee, United States, 37421
United States, Texas
Akero Clinical Study Site
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
Puerto Rico
Akero Clinical Study Site
San Juan, Puerto Rico, 00927
Sponsors and Collaborators
Akero Therapeutics, Inc
  Study Documents (Full-Text)

Documents provided by Akero Therapeutics, Inc:
Study Protocol  [PDF] October 8, 2020
Statistical Analysis Plan: Main Study  [PDF] March 4, 2020
Statistical Analysis Plan: Cohort C  [PDF] March 5, 2021

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Akero Therapeutics, Inc
ClinicalTrials.gov Identifier: NCT03976401    
Other Study ID Numbers: AK-US-001-0101
First Posted: June 6, 2019    Key Record Dates
Results First Posted: August 4, 2022
Last Update Posted: August 4, 2022
Last Verified: August 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases