Clinical trial NCT03976401: A Study of Efruxifermin in Subjects With Histologically Confirmed Nonalcoholic Steatohepatitis (NASH)
Official title: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Efruxifermin in Subjects With Nonalcoholic Steatohepatitis (NASH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: NASH - Nonalcoholic Steatohepatitis
Lead sponsor: Akero Therapeutics, Inc
Sponsor class: INDUSTRY
First posted: 2019-06-06
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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).

Primary outcomes:
measure: Main: Absolute Change From Baseline in Hepatic Fat Fraction Assessed by MRI-PDFF at Week 12.
timeFrame: 12 weeks
Secondary outcomes:
measure: Main: Absolute Change From Baseline in Hepatic Fat Fraction Assessed by MRI-PDFF at Week 22-24.
timeFrame: 22-24 weeks
measure: Main: Percent Change From Baseline in Hepatic Fat Fraction Measured by MRI-PDFF at Week 12.
timeFrame: 12 weeks
measure: Main: Percent Change From Baseline in Hepatic Fat Fraction Measured by MRI-PDFF at Week 22-24.
timeFrame: 22-24 weeks
measure: 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.
timeFrame: 12 weeks
measure: 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.
timeFrame: 22-24 weeks
measure: Main: Change From Baseline in ALT at Week 12, 16, and 20.
timeFrame: 12, 16, and 20 weeks
measure: Cohort C: Change From Baseline in Liver Stiffness as Evaluated by FibroScan at Week 16
timeFrame: 16 weeks
measure: Cohort C: Change From Baseline in Non-invasive Biomarkers Including Pro-C3 at Week 12, 16, and 20.
timeFrame: 12, 16, and 20 weeks
measure: Cohort C: Change From Baseline in Non-invasive Biomarkers Including Liver Fibrosis by ELF Test Score at Week 12 and 16.
timeFrame: 12 and 16 weeks
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Akero Clinical Study Site
state: Arizona
city: Little Rock
country: United States
facility: Akero Clinical Study Site
state: Arkansas
city: Huntington Park
country: United States
facility: Akero Clinical Study Site
state: California
city: Los Angeles
country: United States
facility: Akero Clinical Study Site
state: California
city: Los Angeles
country: United States
facility: Akero Clinical Study Site
state: California
city: Panorama City
country: United States
facility: Akero Clinical Study Site
state: California
city: Poway
country: United States
facility: Akero Clinical Study Site
state: California
city: Boca Raton
country: United States
facility: Akero Clinical Study Site
state: Florida
city: Lakewood Ranch
country: United States
facility: Akero Clinical Study Site
state: Florida
city: Miami
country: United States
facility: Akero Clinical Study Site
state: Florida
city: New Port Richey
country: United States
facility: Akero Clinical Study Site
state: Florida
city: Ocoee
country: United States
facility: Akero Clinical Study Site
state: Florida
city: Port Orange
country: United States
facility: Akero Clinical Study Site
state: Florida
city: Sarasota
country: United States
facility: Akero Clinical Study Site
state: Florida
city: Baton Rouge
country: United States
facility: Akero Clinical Study Site
state: Louisiana
city: Marrero
country: United States
facility: Akero Clinical Study Site
state: Louisiana
city: Kansas City
country: United States
facility: Akero Clinical Study Site
state: Missouri
city: Berlin
country: United States
facility: Akero Clinical Study Site
state: New Jersey
city: Chattanooga
country: United States
facility: Akero Clinical Study Site
state: Tennessee
city: Cedar Park
country: United States
facility: Akero Clinical Study Site
state: Texas
city: Dallas
country: United States
facility: Akero Clinical Study Site
state: Texas
city: Edinburg
country: United States
facility: Akero Clinical Study Site
state: Texas
city: Fort Worth
country: United States
facility: Akero Clinical Study Site
state: Texas
city: San Antonio
country: United States
facility: Akero Clinical Study Site
state: Texas
city: San Antonio
country: United States
facility: Akero Clinical Study Site
state: Texas
city: Webster
country: United States
facility: Akero Clinical Study Site
state: Texas
city: San Juan
country: Puerto Rico
facility: Akero Clinical Study Site
Study officials:
References:
citation: Harrison SA, Ruane PJ, Freilich BL, Neff G, Patil R, Behling CA, Hu C, Fong E, de Temple B, Tillman EJ, Rolph TP, Cheng A, Yale K. Efruxifermin in non-alcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a trial. Nat Med. 2021 Jul;27(7):1262-1271. doi: 10.1038/s41591-021-01425-3. Epub 2021 Jul 8.