A Study Evaluating Efruxifermin in Subjects With Non-Cirrhotic Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis

Phase 3RecruitingNCT06215716

Akero Therapeutics, Inc1,650 enrolled

Overview

This is a multi-center evaluation of efruxifermin (EFX) in a randomized, double-blind, placebo-controlled study in subjects with non-cirrhotic NASH/MASH and fibrosis stage 2 or 3 (F2 or F3). The study will enroll subjects in two cohorts for a total samples size of 1650 subjects.

This is a Phase 3, multi-center, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of efruxifermin (EFX) in subjects with non-cirrhotic nonalcoholic steatohepatitis (NASH)/metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis stage 2 or 3 (F2 or F3). Approximately 1,650 subjects will be enrolled into 2 cohorts. * 750 F2/F3 subjects in Cohort 1 * 900 F3 subjects in Cohort 2 Cohort 1 will enroll approximately 750 subjects with biopsy-confirmed NASH/MASH and fibrosis stage F2 or F3. Subjects in Cohort 1 will undergo evaluation of histologic efficacy endpoints at Week 52. Cohort 2 will enroll approximately 900 subjects with biopsy-confirmed fibrosis stage F3. Subjects in Cohort 2 may enroll regardless of NAFLD Activity Score (NAS). Subjects in Cohort 2 will undergo liver biopsy assessment at Week 96. Eligible subjects will be randomized in a 1:1:1 ratio to receive: * EFX 28 mg administered subcutaneously once weekly * EFX 50 mg administered subcutaneously once weekly * Placebo administered subcutaneously once weekly Subjects will participate in: * a screening period of up to 12 weeks, * a 52-week primary histology endpoint treatment period, * long-term treatment and clinical outcomes follow-up for up to approximately -240 weeks total treatment duration, and * a follow-up visit approximately 30 days after the last dose of study drug. The study will evaluate the effects of EFX compared with placebo on histologic improvement in NASH/MASH, fibrosis regression, progression to cirrhosis, noninvasive markers of liver fibrosis, liver-related clinical outcomes, and long-term safety. Clinical outcomes assessments include evaluation of liver-related events and all-cause mortality. Key secondary and long-term outcome assessments include evaluation of fibrosis progression, liver stiffness by FibroScan, Enhanced Liver Fibrosis (ELF) score, and progression to cirrhosis at prespecified time points including Weeks 96 and 240. An interim analysis of the primary clinical outcomes endpoint may be performed after all subjects in Cohort 2 have completed the Week 96 visit or discontinued from the study and a prespecified number of clinical outcome events have occurred. Subjects who discontinue study drug may continue study assessments according to the protocol schedule to support long-term efficacy and safety evaluations.

Study Type

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Males and non-pregnant, non-lactating females between 18 - 80 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. * Cohort 1: Biopsy-proven NASH/MASH. Must have had a liver biopsy obtained ≤ 180 days prior to screening with fibrosis stage 2 or 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 2: Biopsy-proven fibrosis stage 3. Must have had a liver biopsy obtained ≤ 180 days prior to screening. Subjects with NAS \<4 may be enrolled and are not required to meet 1 point in each of the components of NAS. Exclusion Criteria: * Other causes of liver disease based on medical history and/or liver histology and/or central laboratory results. * Presence of cirrhosis on liver biopsy (fibrosis stage 4). * Type 1 or uncontrolled Type 2 diabetes. Other inclusion and exclusion criteria may apply.

Locations (356)

Akero Clinical Study Site

Birmingham, Alabama, United States

RECRUITING

Akero Clinical Study Site

Dothan, Alabama, United States

RECRUITING

Akero Clinical Study Site

Chandler, Arizona, United States

RECRUITING

Akero Clinical Study Site

Flagstaff, Arizona, United States

Outcomes

Primary Outcomes

Cohort 1 Only: Resolution of NASH/MASH and a ≥ 1 stage improvement in fibrosis

Based on NAS (scored by 0-1 for steatosis, 0-3 for inflammation, and 0-2 for ballooning) and NASH CRN fibrosis score (scored by a fibrosis score of 0-4, where 0 = no fibrosis, 1 = centrilobular pericellular fibrosis, 2 = centrilobular and periportal fibrosis, 3 = bridging fibrosis, 4 = cirrhosis)

Time frame: 52 Weeks

Event-free survival

Based on time from randomization to the first clinical event including evidence of disease progression, liver decompensation events, liver transplantation or eligibility for liver transplantation, and all-cause mortality.

Time frame: 240 Weeks

Secondary Outcomes

Cohort 1 Only: Resolution of NASH/MASH and no worsening of fibrosis

Time frame: 52 Weeks

Cohort 1 Only: ≥ 1 stage improvement in fibrosis and no worsening of steatohepatitis

Time frame: 52 Weeks

Resolution of NASH/MASH and no worsening of fibrosis

Time frame: 96 Weeks, 240 Weeks

Change from baseline of non-invasive markers of liver fibrosis: ELF score

ELF (scale of 6.7 to 9.8 when higher scores indicative of increased fibrosis)

Time frame: 52 Weeks

Change from baseline of non-invasive markers of liver fibrosis: ELF score components (TIMP-1, HA, PIIINP, Pro-C3)

Tissue inhibitor of metalloproteinase-1 \[TIMP-1\], hyaluronic acid \[HA\], amino terminal pro-peptide of type 3 procollagen \[PIIINP\]), and propeptide of type 3 procollagen (Pro-C3)

Time frame: 52 Weeks

Change from baseline in non-invasive markers of liver fibrosis: ELF score

ELF score scale of 6.7 to 9.8 when higher scores are indicative of increased fibrosis

Time frame: 96 Weeks, 240 Weeks

Change from baseline in non-invasive markers of liver fibrosis: ELF score components: TIMP-1, HA, PIIINP, Pro-C3

Time frame: Week 240

Change from baseline of non-invasive markers of liver fibrosis: Fibroscan, CAP

Liver stiffness assessed by transient elastography (FibroScan®) (kPa, CAP)

Time frame: 52 Weeks

Change from baseline of non-invasive markers of liver fibrosis: Fibroscan

Liver stiffness assessed by transient elastography (FibroScan)

Time frame: 96 Weeks, 240 Weeks

Change from baseline of markers of liver injury: ALT, AST, GGT

ALT (U/L), AST (U/L), GGT (U/L)