- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03976401
A Study of Efruxifermin in Subjects With Histologically Confirmed Nonalcoholic Steatohepatitis (NASH)
A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Efruxifermin in Subjects With Nonalcoholic Steatohepatitis (NASH)
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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San Juan, Puerto Rico, 00927
- Akero Clinical Study Site
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Arizona
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Tucson, Arizona, United States, 85711
- Akero Clinical Study Site
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Arkansas
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Little Rock, Arkansas, United States, 72117
- Akero Clinical Study Site
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California
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Huntington Park, California, United States, 90255
- Akero Clinical Study Site
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Los Angeles, California, United States, 90036
- Akero Clinical Study Site
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Los Angeles, California, United States, 90057
- Akero Clinical Study Site
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Panorama City, California, United States, 91402
- Akero Clinical Study Site
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Poway, California, United States, 92064
- Akero Clinical Study Site
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Florida
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Boca Raton, Florida, United States, 33434
- Akero Clinical Study Site
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Lakewood Ranch, Florida, United States, 34211
- Akero Clinical Study Site
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Miami, Florida, United States, 33156
- Akero Clinical Study Site
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New Port Richey, Florida, United States, 34653
- Akero Clinical Study Site
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Ocoee, Florida, United States, 34761
- Akero Clinical Study Site
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Port Orange, Florida, United States, 32127
- Akero Clinical Study Site
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Sarasota, Florida, United States, 34240
- Akero Clinical Study Site
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Louisiana
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Baton Rouge, Louisiana, United States, 70809
- Akero Clinical Study Site
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Marrero, Louisiana, United States, 70072
- Akero Clinical Study Site
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Missouri
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Kansas City, Missouri, United States, 64131
- Akero Clinical Study Site
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New Jersey
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Berlin, New Jersey, United States, 08009
- Akero Clinical Study Site
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Tennessee
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Chattanooga, Tennessee, United States, 37421
- Akero Clinical Study Site
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Texas
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Cedar Park, Texas, United States, 78613
- Akero Clinical Study Site
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Dallas, Texas, United States, 75246
- Akero Clinical Study Site
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Edinburg, Texas, United States, 78539
- Akero Clinical Study Site
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Fort Worth, Texas, United States, 76104
- Akero Clinical Study Site
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San Antonio, Texas, United States, 78215
- Akero Clinical Study Site
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San Antonio, Texas, United States, 78229
- Akero Clinical Study Site
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Webster, Texas, United States, 77598
- Akero Clinical Study Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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
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Administered by subcutaneous injection
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EXPERIMENTAL: EFX Dose 2
Main Study
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Administered by subcutaneous injection
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EXPERIMENTAL: EFX Dose 3
Main Study
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Administered by subcutaneous injection
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PLACEBO_COMPARATOR: Placebo
Main Study
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Administered by subcutaneous injection
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EXPERIMENTAL: EFX Dose (Cohort C)
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Administered by subcutaneous injection
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PLACEBO_COMPARATOR: Placebo (Cohort C)
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Administered by subcutaneous injection
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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
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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.
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12 weeks
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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
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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.
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22-24 weeks
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Main: Percent Change From Baseline in Hepatic Fat Fraction Measured by MRI-PDFF at Week 12.
Time Frame: 12 weeks
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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.
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12 weeks
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Main: Percent Change From Baseline in Hepatic Fat Fraction Measured by MRI-PDFF at Week 22-24.
Time Frame: 22-24 weeks
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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.
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22-24 weeks
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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
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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.
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12 weeks
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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
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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.
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22-24 weeks
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Main: Change From Baseline in ALT at Week 12, 16, and 20.
Time Frame: 12, 16, and 20 weeks
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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.
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12, 16, and 20 weeks
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Cohort C: Change From Baseline in Liver Stiffness as Evaluated by FibroScan at Week 16
Time Frame: 16 weeks
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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.
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16 weeks
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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
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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.
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12, 16, and 20 weeks
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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
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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
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- AK-US-001-0101
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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