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

Résumé

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.

Éligibilité

Conception de l'étude

Critères de jugement

1. Critère de jugement principal

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

   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)

   Délai 52 Weeks

2. Critère de jugement principal

   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.

   Délai 240 Weeks

3. Critère de jugement secondaire

   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)

   Délai 52 Weeks

4. Critère de jugement secondaire

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

   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)

   Délai 52 Weeks

5. Critère de jugement secondaire

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

   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)

   Délai 52 Weeks

6. Critère de jugement secondaire

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

   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.

   Délai 52 Weeks

7. Critère de jugement secondaire

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

   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.

   Délai 96 Weeks, 240 Weeks

8. Critère de jugement secondaire

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

   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.

   Délai Week 240

9. Critère de jugement secondaire

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

   Liver stiffness assessed by transient elastography (FibroScan)

   Délai 52 Weeks

10. Critère de jugement secondaire

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

    Liver stiffness assessed by transient elastography (FibroScan)

    Délai 96 Weeks, 240 Weeks

11. Critère de jugement secondaire

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

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

    Délai 52 Weeks, 240 Weeks

12. Critère de jugement secondaire

    Change from baseline of markers of liver injury: Uric Acid

    Uric acid (mg/dL)

    Délai 52 Weeks, 240 Weeks

13. Critère de jugement secondaire

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

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

    Délai 52 Weeks, 240 Weeks

14. Critère de jugement secondaire

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

    HbA1c (%)

    Délai 52 Weeks, 240 Weeks

15. Critère de jugement secondaire

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

    Adiponectin (mg/L)

    Délai 52 Weeks, 240 Weeks

16. Critère de jugement secondaire

    Change from baseline of body weight (kg)

    Délai 52 Weeks, 240 Weeks

17. Critère de jugement secondaire

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

    Délai 52 Weeks, 240 Weeks

18. Critère de jugement secondaire

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

    Délai 52 Weeks, 240 Weeks

19. Critère de jugement secondaire

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

    Délai 52 Weeks, 240 Weeks

20. Critère de jugement secondaire

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

    Délai 52 Weeks, 240 Weeks

21. Critère de jugement secondaire

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

    Délai 52 Weeks, 240 Weeks

Dates

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Lieux

319 sites sont en recrutement

306 sites supplémentaires sont indiqués dans la fiche du registre.

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