A Study Evaluating Efruxifermin in Subjects With Non-invasively Diagnosed Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Nonalcoholic Fatty Liver Disease (NAFLD)/Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Study Overview
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Brief Summary
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This is a multi-center evaluation of efruxifermin (EFX) in a randomized, double-blind, placebo-controlled study in subjects with noninvasively diagnosed NASH/MASH or NAFLD/MASLD

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Efruxifermin in Subjects With Non-invasively Diagnosed Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Nonalcoholic Fatty Liver Disease (NAFLD)/Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Conditions
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NASH/MASH, NAFLD/MASLD

Intervention / Treatment
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* Drug: Efruxifermin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Main Study Only: 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. Suspected or confirmed diagnosis of NASH/MASH or NAFLD/MASLD or non-invasively diagnosed NASH/MASH or NAFLD/MASLD Open-Label Rollover Prior participation in the placebo arm of a previous Akero Phase 2 study Exclusion Criteria: Other causes of liver disease based on medical history and/or liver histology and/or central laboratory results Type 1 or unstable Type 2 diabetes Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EFX 50 mg<br> | Drug: Efruxifermin<br>* Administered by subcutaneous injection<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Administered by subcutaneous injection<br>|
| Experimental: EFX 50 mg (Open-Label)<br> | Drug: Efruxifermin<br>* Administered by subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety and tolerability of EFX | Safety and tolerability will be assessed through the reporting of extent of exposure (weeks), adverse events (frequency & severity of events), clinical laboratory tests, ECGs, ultrasounds, vital sign assessments, and concomitant medication usage. | 52 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of non-invasive markers of liver fibrosis | FAST score (varied on a scale from 0 to 1, with the patients being classified as having low (<0.35), intermediate (0.35-0.67), or high (>0.67) probability of having significant inflammatory activity and fibrosis), ELF (scale of 6.7 to 9.8 where higher scores indicative of increased fibrosis), Pro-C3 (ug/L), and liver stiffness assessed by transient elastography (kPa, CAP) | 52 Weeks | 
| Change from baseline of lipoproteins | Total cholesterol (mg/dL), Triglycerides (mg/dL), HDL-C (mg/dL), Non-HDL-C (mg/dL), LDL-C (mg/dL) | 52 Weeks | 
| Change from baseline of markers of glycemic control | HbA1c (%) and Adiponectin (mg/L) | 52 Weeks | 
| Change from baseline of markers of liver injury | ALT (U/L), AST (U/L), GGT (U/L), and uric acid (mg/dL) | 52 Weeks | 
| Change from baseline of body weight (kg) |  | 52 Weeks |