Title
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)
Phase
Phase 2Lead Sponsor
Akero Therapeutics, IncStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
NASH - Nonalcoholic SteatohepatitisIntervention/Treatment
amg 876 ...Study Participants
110This 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.
Administered by subcutaneous injection
Administered by subcutaneous injection
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).
| Event Type | Organ System | Event Term | Main Study EFX 28 mg | Main Study EFX 50 mg | Main Study EFX 70 mg | Main Study Placebo | Cohort C EFX 50 mg | Cohort C Placebo |
|---|
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 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 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 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 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.
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.
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: 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.
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.
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.
