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

NCT03976401 | Completed Phase 2 Results FDA Drug

• 1 other identifier: AK-US-001-0101
• Study Type: interventional
• Target: 110
• Locations: 2 countries
• Sites: 27

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.

Conditions

NASH - Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• Main: Absolute Change From Baseline in Hepatic Fat Fraction Assessed by MRI-PDFF at Week 12.

  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.

  12 weeks

Secondary Outcomes (9)

• Main: Absolute Change From Baseline in Hepatic Fat Fraction Assessed by MRI-PDFF at Week 22-24.

  22-24 weeks

• Main: Percent Change From Baseline in Hepatic Fat Fraction Measured by MRI-PDFF at Week 12.

  12 weeks

• Main: Percent Change From Baseline in Hepatic Fat Fraction Measured by MRI-PDFF at Week 22-24.

  22-24 weeks

• 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.

  12 weeks

• 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.

  22-24 weeks

Study Arms (6)

EFX Dose 1

EXPERIMENTAL

Main Study

Drug: EFX

EFX Dose 2

EXPERIMENTAL

Main Study

Drug: EFX

EFX Dose 3

EXPERIMENTAL

Main Study

Drug: EFX

Placebo

PLACEBO COMPARATOR

Main Study

Drug: Placebo

EFX Dose (Cohort C)

EXPERIMENTAL

Drug: EFX

Placebo (Cohort C)

PLACEBO COMPARATOR

Drug: Placebo

Interventions

EFX DRUG

Administered by subcutaneous injection

EFX Dose (Cohort C); EFX Dose 1; EFX Dose 2; EFX Dose 3

Placebo DRUG

Administered by subcutaneous injection

Placebo; Placebo (Cohort C)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Akero Therapeutics, Inc: lead

Study Sites (27)

Akero Clinical Study Site

Tucson, Arizona, 85711, United States

Location

Akero Clinical Study Site

Little Rock, Arkansas, 72117, United States

Location

Akero Clinical Study Site

Huntington Park, California, 90255, United States

Location

Akero Clinical Study Site

Los Angeles, California, 90036, United States

Location

Akero Clinical Study Site

Los Angeles, California, 90057, United States

Location

Akero Clinical Study Site

Panorama City, California, 91402, United States

Location

Akero Clinical Study Site

Poway, California, 92064, United States

Location

Akero Clinical Study Site

Boca Raton, Florida, 33434, United States

Location

Akero Clinical Study Site

Lakewood Rch, Florida, 34211, United States

Location

Akero Clinical Study Site

Miami, Florida, 33156, United States

Location

Akero Clinical Study Site

New Port Richey, Florida, 34653, United States

Location

Akero Clinical Study Site

Ocoee, Florida, 34761, United States

Location

Akero Clinical Study Site

Port Orange, Florida, 32127, United States

Location

Akero Clinical Study Site

Sarasota, Florida, 34240, United States

Location

Akero Clinical Study Site

Baton Rouge, Louisiana, 70809, United States

Location

Akero Clinical Study Site

Marrero, Louisiana, 70072, United States

Location

Akero Clinical Study Site

Kansas City, Missouri, 64131, United States

Location

Akero Clinical Study Site

Berlin, New Jersey, 08009, United States

Location

Akero Clinical Study Site

Chattanooga, Tennessee, 37421, United States

Location

Akero Clinical Study Site

Cedar Park, Texas, 78613, United States

Location

Akero Clinical Study Site

Dallas, Texas, 75246, United States

Location

Akero Clinical Study Site

Edinburg, Texas, 78539, United States

Location

Akero Clinical Study Site

Fort Worth, Texas, 76104, United States

Location

Akero Clinical Study Site

San Antonio, Texas, 78215, United States

Location

Akero Clinical Study Site

San Antonio, Texas, 78229, United States

Location

Akero Clinical Study Site

Webster, Texas, 77598, United States

Location

Akero Clinical Study Site

San Juan, 00927, Puerto Rico

Location

Related Publications (3)

• Alkhouri N, Beyer C, Shumbayawonda E, Andersson A, Yale K, Rolph T, Chung RT, Vuppalanchi R, Cusi K, Loomba R, Pansini M, Dennis A. Decreases in cT1 and liver fat content reflect treatment-induced histological improvements in MASH. J Hepatol. 2025 Mar;82(3):438-445. doi: 10.1016/j.jhep.2024.08.031. Epub 2024 Sep 25.

  PMID: 39326675 DERIVED

• Harrison SA, Ruane PJ, Freilich B, Neff G, Patil R, Behling C, Hu C, Shringarpure R, de Temple B, Fong E, Tillman EJ, Rolph T, Cheng A, Yale K. A randomized, double-blind, placebo-controlled phase IIa trial of efruxifermin for patients with compensated NASH cirrhosis. JHEP Rep. 2022 Aug 23;5(1):100563. doi: 10.1016/j.jhepr.2022.100563. eCollection 2023 Jan.

  PMID: 36644237 DERIVED

• 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.

  PMID: 34239138 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Brittany de Temple, Senior Director Clinical Operations
• Organization: Akero Therapeutics, Inc.

brittany@akerotx.com

(650) 868-7935

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2019
• First Posted: June 6, 2019
• Study Start: May 28, 2019
• Primary Completion: February 10, 2021
• Study Completion: January 10, 2022
• Last Updated: August 4, 2022
• Results First Posted: August 4, 2022

Record last verified: 2022-08

Locations

US (26); PR (1)