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

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 non-cirrhotic subjects with biopsy-proven F2 - F3 NASH.

Official Title
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A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Efruxifermin in Non-Cirrhotic Subjects With Nonalcoholic Steatohepatitis (NASH)

Conditions
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NASH - Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Drug: EFX
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and non-pregnant, non-lactating females between 18 - 75 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. FibroScan® measurement > 8.5 kPa. Biopsy-proven NASH. Must have had a liver biopsy obtained ≤ 180 days prior to randomization with fibrosis stage 2 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). Exclusion Criteria: Weight loss > 5% in the 3 months prior to screening until randomization or from the time of the diagnostic liver biopsy until randomization, whichever is longer. Presence of cirrhosis on liver biopsy (stage 4 fibrosis). Type 1 or uncontrolled Type 2 diabetes. Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 28 mg<br> | Drug: EFX<br>* Administered by subcutaneous injection<br>|
| Experimental: EFX 50 mg<br> | Drug: EFX<br>* Administered by subcutaneous injection<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Administered by subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in liver fibrosis with no worsening steatohepatitis assessed by NASH CRN system |  | 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resolution of steatohepatitis with no worsening of fibrosis assessed by the NASH CRN system |  | 24 Weeks, 96 Weeks | 
| Change from baseline in liver fibrosis with no worsening of steatohepatitis assessed by the NASH CRN system |  | 96 Weeks | 
| Responder based on NASH CRN: patients who had a decrease of ≥ one point in fibrosis score |  | 24 Weeks, 96 Weeks | 
| Change from baseline in hepatic fat fraction |  | 24 Weeks, 96 Weeks | 
| Change from baseline of lipoproteins - Non-HDL-C, HDL-C, and LDL-C |  | 24 Weeks, 48 Weeks, 96 Weeks | 
| Change from baseline of markers of glycemic control - HbA1c |  | 24 Weeks, 48 Weeks, 96 Weeks | 
| Change from baseline of markers of glycemic control - C-Peptide |  | 24 Weeks, 48 Weeks, 96 Weeks | 
| Change from baseline of markers of glycemic control - Adiponectin |  | 24 Weeks, 48 Weeks, 96 Weeks | 
| Change from baseline of markers of glycemic control - HOMA-IR |  | 24 Weeks, 48 Weeks, 96 Weeks | 
| Change from baseline of non-invasive fibrosis biomarkers - ELF |  | 24 Weeks, 48 Weeks, 96 Weeks | 
| Change from baseline of non-invasive fibrosis biomarkers - Pro-C3 |  | 24 Weeks, 48 Weeks, 96 Weeks | 
| Change from baseline of non-invasive fibrosis biomarkers - NIS-4 |  | 24 Weeks, 48 Weeks, 96 Weeks | 
| Change from baseline of non-invasive fibrosis biomarkers - liver stiffness assessed by transient elastography (FibroScan®) |  | 24 Weeks, 48 Weeks, 96 Weeks | 
| Change from baseline of body weight |  | 24 Weeks, 48 Weeks, 96 Weeks |