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

NCT06215716
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Phase
Phase 3
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Recruitment status
Recruiting
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Participants
1,650
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Lead sponsor
Akero Therapeutics, Inc
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Start date
2023-12-01
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Number of sites
356
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Summary
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.
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Short title
A Study Evaluating Efruxifermin in Subjects With Non-Cirrhotic Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis
clinicaltrials.gov
Official title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Efruxifermin in Subjects With Non-Cirrhotic Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis
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Control arm
Placebo
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2033-02-01
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First posted
2024-01-22
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Registry last updated
2026-08-07
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Primary completion date
2033-02-01
clinicaltrials.gov
Start date
2023-12-01
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Participants
1,650
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Participant count basis
Estimated
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Planned participants
1,650
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Protocol amendments
5
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Randomisation ratio
1:1:1
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Number of sites
356
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Registry sponsor category
Industry
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Lead sponsor
Akero Therapeutics, Inc
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06215716
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ClinicalTrials.gov ID
NCT06215716
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Quadruple masking
Masked roles
Participants, Care providers, Investigators, Outcome assessors
Sources for study design
clinicaltrials.gov

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

    Timeframe: 52 Weeks

    Based on NAS (scored by 0-3 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 = perisinusoidal or periportal fibrosis, 2 = perisinusoidal and portal/periportal fibrosis, 3 = bridging fibrosis, 4 = cirrhosis)

  2. Event-free survival

    Timeframe: 240 Weeks

    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.

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

    Timeframe: 52 Weeks

    Based on NAS (scored by 0-3 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 = perisinusoidal or periportal fibrosis, 2 = perisinusoidal and portal/periportal fibrosis, 3 = bridging fibrosis, 4 = cirrhosis)

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

    Timeframe: 52 Weeks

    Based on NAS (scored by 0-3 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 = perisinusoidal or periportal fibrosis, 2 = perisinusoidal and portal/periportal fibrosis, 3 = bridging fibrosis, 4 = cirrhosis)

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

    Timeframe: 52 Weeks

    The ELF score measures the severity of liver fibrosis and estimates the risk of disease progression to cirrhosis or liver-related events, with higher scores indicating higher liver fibrosis level and higher risk of disease progression.

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

    Timeframe: 52 Weeks

    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)

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

    Timeframe: 96 Weeks, 240 Weeks

    The ELF score measures the severity of liver fibrosis and estimates the risk of disease progression to cirrhosis or liver-related events, with higher scores indicating higher liver fibrosis level and higher risk of disease progression.

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

    Timeframe: Week 240

    The ELF score measures the severity of liver fibrosis and estimates the risk of disease progression to cirrhosis or liver-related events, with higher scores indicating higher liver fibrosis level and higher risk of disease progression.

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

    Timeframe: 52 Weeks

    Liver stiffness assessed by transient elastography (FibroScan)

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

    Timeframe: 96 Weeks, 240 Weeks

    Liver stiffness assessed by transient elastography (FibroScan)

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

    Timeframe: 52 Weeks, 240 Weeks

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

  10. Change from baseline of markers of liver injury: Uric Acid

    Timeframe: 52 Weeks, 240 Weeks

    Uric acid (mg/dL)

  11. Change from baseline of lipoproteins: Total cholesterol, TG, Non-HDL-C, HDL-C, and LDL-C

    Timeframe: 52 Weeks, 240 Weeks

    Total cholesterol (mg/dL), TG (mg/dL), Non-HDL-C (mg/dL), HDL-C (mg/dL), and LDL-C (mg/dL)

  12. Change from baseline of markers of insulin sensitivity and glycemic control: HbA1c

    Timeframe: 52 Weeks, 240 Weeks

    HbA1c (%)

  13. Change from baseline of markers of insulin sensitivity and glycemic control: Adiponectin

    Timeframe: 52 Weeks, 240 Weeks

    Adiponectin (mg/L)

  14. Change from baseline of body weight (kg)

    Timeframe: 52 Weeks, 240 Weeks

  15. To assess the safety and tolerability of EFX through the reporting of extent of exposure (weeks)

    Timeframe: 52 Weeks, 240 Weeks

  16. To assess the safety and tolerability of EFX through the reporting of adverse events (severity of events)

    Timeframe: 52 Weeks, 240 Weeks

  17. To assess the safety and tolerability of EFX through the reporting of adverse events (frequency of events)

    Timeframe: 52 Weeks, 240 Weeks

  18. To assess the safety and tolerability of EFX through the reporting of abnormal clinical laboratory tests, ECGs, ultrasounds, vital sign assessments (number of patients)

    Timeframe: 52 Weeks, 240 Weeks

  19. To assess the immunogenicity of EFX through the reporting of antidrug antibodies (number of patients)

    Timeframe: 52 Weeks, 240 Weeks

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Maximum age
80 Years
Healthy volunteers
No

  • 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.

  • 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.

Sources for eligibility
clinicaltrials.gov

  • Akero Clinical Study SiteBirmingham, United StatesRecruiting
  • Akero Clinical Study SiteDothan, United StatesRecruiting
  • Akero Clinical Study SiteChandler, United StatesRecruiting
  • Akero Clinical Study SiteFlagstaff, United StatesCompleted
  • Akero Clinical Study SitePeoria, United StatesRecruiting
  • Akero Clinical Study SiteTucson, United StatesRecruiting
  • Akero Clinical Study SiteTucson, United StatesRecruiting
  • Akero Clinical Study SiteTucson, United StatesRecruiting
  • Akero Clinical Study SiteTucson, United StatesRecruiting
  • Akero Clinical Study SiteConway, United StatesCompleted
  • Akero Clinical Study SiteJonesboro, United StatesCompleted
  • Akero Clinical Study SiteLittle Rock, United StatesRecruiting
  • Akero Clinical Study SiteNorth Little Rock, United StatesRecruiting
  • Akero Clinical Study SiteChula Vista, United StatesCompleted
  • Akero Clinical Study SiteCoronado, United StatesRecruiting
  • Akero Clinical Study SiteEscondido, United StatesRecruiting
  • Akero Clinical Study SiteFolsom, United StatesRecruiting
  • Akero Clinical Study SiteInglewood, United StatesRecruiting
  • Akero Clinical Study SiteLa Mesa, United StatesCompleted
  • Akero Clinical Study SiteLancaster, United StatesCompleted
  • Akero Clinical Study SiteLancaster, United StatesRecruiting
  • Akero Clinical Study SiteLong Beach, United StatesRecruiting
  • Akero Clinical Study SiteLos Angeles, United StatesCompleted
  • Akero Clinical Study SiteLos Angeles, United StatesRecruiting
  • Akero Clinical Study SiteLos Angeles, United StatesRecruiting

And 331 more, listed on the interactive page.

Sources for sites
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Related records

Drugs (1)

Lead sponsors (1)