Clinical trial NCT04767529: A Study of Efruxifermin in Non-Cirrhotic Subjects With Histologically Confirmed Nonalcoholic Steatohepatitis (NASH)
Official title: A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Efruxifermin in Non-Cirrhotic 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: 2021-02-23
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
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 in non-cirrhotic subjects with biopsy-proven F2 - F3 NASH.


Eligibility criteria: Inclusion Criteria:

* Males and non-pregnant, non-lactating females between 18 - 75 years of age inclusive, based on the date of the screening visit.
* Previous history or presence of 2 out of 4 components of metabolic syndrome (obesity, dyslipidemia, elevated blood pressure, elevated fasting glucose) or type 2 diabetes.
* FibroScan measurement \> 8.5 kPa \[kilopascal\].
* Biopsy-proven NASH. Must have had a liver biopsy obtained ≤ 180 days prior to randomization with fibrosis stage 2 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).

Exclusion Criteria:

* Weight loss \> 5% in the 3 months prior to screening until randomization or from the time of the diagnostic liver biopsy until randomization, whichever is longer.
* Presence of cirrhosis on liver biopsy (stage 4 fibrosis).
* Type 1 or uncontrolled Type 2 diabetes.

Other inclusion and exclusion criteria may apply.

Primary outcomes:
measure: Effect of Efruxifermin (EFX) vs Placebo on Fibrosis Regression in Participants With Metabolic Dysfunction-associated Steatohepatitis (MASH)-Associated Stage 2 or 3 Fibrosis (F2 or F3)
timeFrame: 24 Weeks
Secondary outcomes:
measure: Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage and no Worsening of Steatohepatitis at Week 96
timeFrame: 96 Weeks
measure: Proportion of Subjects Who Achieve Resolution of Steatohepatitis and no Worsening of Liver Fibrosis at Week 24 and Week 96
timeFrame: 24 and 96 weeks
measure: Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage at Week 24 and Week 96
timeFrame: 24 and 96 Weeks
measure: Change From Baseline in Hepatic Fat Fraction in EFX vs Placebo Groups
timeFrame: 24 and 96 Weeks
measure: Change From Baseline in Lipoproteins at Week 24 and Week 96
timeFrame: 24 and 96 weeks
measure: Change From Baseline of Hemoglobin A1c (Glycated Hemoglobin, HbA1c) at Week 24 and Week 96
timeFrame: 24 Weeks, 96 Weeks
measure: Change From Baseline in C-peptide at Week 24 and Week 96
timeFrame: 24 Weeks, 96 Weeks
measure: Change From Baseline in Adiponectin at Week 24 and Week 96
timeFrame: 24 Weeks, 96 Weeks
measure: Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 24 and Week 96
timeFrame: 24 Weeks, 96 Weeks
measure: Change From Baseline in Enhanced Liver Fibrosis (ELF) Score at Week 24 and Week 96
timeFrame: 24 and 96 Weeks
measure: Change From Baseline in N-terminal Type III Collagen Propeptide (Pro-C3) at Week 24 and Week 96
timeFrame: 24 and 96 Weeks
measure: Change From Baseline in Collagen III Neo-Peptide (C3M) at Week 24 and Week 96
timeFrame: 24 and 96 Weeks
measure: Change From Baseline in NIS4 Score at Week 24 and Week 96
timeFrame: 24 and 96 Weeks
measure: Change in Body Weight at Week 24 and Week 96
timeFrame: 24 and 96 weeks
measure: Change From Baseline in Liver Stiffness (kPa) at Week 24 and Week 96
timeFrame: 24 and 96 weeks
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Akero Clinical Study Site
state: Arizona
city: Glendale
country: United States
facility: Akero Clinical Study Site
state: Arizona
city: Tucson
country: United States
facility: Akero Clinical Study Site
state: Arizona
city: North Little Rock
country: United States
facility: Akero Clinical Study Site
state: Arkansas
city: Chula Vista
country: United States
facility: Akero Clinical Study Site
state: California
city: Fresno
country: United States
facility: Akero Clinical Study Site
state: California
city: La Jolla
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: Los Angeles
country: United States
facility: Akero Clinical Study Site
state: California
city: Orange
country: United States
facility: Akero Clinical Study Site
state: California
city: Panorama City
country: United States
facility: Akero Clinical Study Site
state: California
city: Rialto
country: United States
facility: Akero Clinical Study Site
state: California
city: Santa Ana
country: United States
facility: Akero Clinical Study Site
state: California
city: Fort Myers
country: United States
facility: Akero Clinical Study Site
state: Florida
city: Inverness
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 Lakes
country: United States
facility: Akero Clinical Study Site
state: Florida
city: Miami
country: United States
facility: Akero Clinical Study Site
state: Florida
city: Miami
country: United States
facility: Akero Clinical Study Site
state: Florida
city: Ocala
country: United States
facility: Akero Clinical Study Site
state: Florida
city: Sarasota
country: United States
facility: Akero Clinical Study Site
state: Florida
city: Marietta
country: United States
facility: Akero Clinical Study Site
state: Georgia
city: Topeka
country: United States
facility: Akero Clinical Study Site
state: Kansas
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: Ypsilanti
country: United States
facility: Akero Clinical Study Site
state: Michigan
city: Flowood
country: United States
facility: Akero Clinical Study Site
state: Mississippi
city: Jackson
country: United States
facility: Akero Clinical Study Site
state: Mississippi
city: Las Vegas
country: United States
facility: Akero Clinical Study Site
state: Nevada
city: Charlotte
country: United States
facility: Akero Clinical Study Site
state: North Carolina
city: Durham
country: United States
facility: Akero Clinical Study Site
state: North Carolina
city: Morehead City
country: United States
facility: Akero Clinical Study Site
state: North Carolina
city: Cincinnati
country: United States
facility: Akero Clinical Study Site
state: Ohio
city: Greenville
country: United States
facility: Akero Clinical Study Site
state: South Carolina
city: Hermitage
country: United States
facility: Akero Clinical Study Site
state: Tennessee
city: Nashville
country: United States
facility: Akero Clinical Study Site
state: Tennessee
city: Arlington
country: United States
facility: Akero Clinical Study Site
state: Texas
city: Austin
country: United States
facility: Akero Clinical Study Site
state: Texas
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: 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: Garland
country: United States
facility: Akero Clinical Study Site
state: Texas
city: Houston
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: San Antonio
country: United States
facility: Akero Clinical Study Site
state: Texas
city: San Marcos
country: United States
facility: Akero Clinical Study Site
state: Texas
city: Webster
country: United States
facility: Akero Clinical Study Site
state: Texas
city: Charlottesville
country: United States
facility: Akero Clinical Study Site
state: Virginia
city: Richmond
country: United States
facility: Akero Clinical Study Site
state: Virginia
city: Richmond
country: United States
facility: Akero Clinical Study Site
state: Virginia
city: San Juan
country: Puerto Rico
facility: Akero Clinical Study Site
Study officials:
affiliation: Study Director
name: Akero Study Director
role: STUDY_DIRECTOR
References:
citation: Harrison SA, Frias JP, Neff G, Abrams GA, Lucas KJ, Sanchez W, Gogia S, Sheikh MY, Behling C, Bedossa P, Shao L, Chan D, Fong E, de Temple B, Shringarpure R, Tillman EJ, Rolph T, Cheng A, Yale K; HARMONY Study Group. Safety and efficacy of once-weekly efruxifermin versus placebo in non-alcoholic steatohepatitis (HARMONY): a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Gastroenterol Hepatol. 2023 Dec;8(12):1080-1093. doi: 10.1016/S2468-1253(23)00272-8. Epub 2023 Oct 3.