Safety, Tolerability, and Efficacy of AXA1125 in NASH With Fibrosis

Study Overview
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Brief Summary
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This study will compare the effects of AXA1125, an orally active mixture of amino acids, compared to placebo, on improving fat and inflammation (steatohepatitis) as well as fibrosis in subjects with non alcoholic steatohepatitis (NASH). as well as the safety and tolerability of AXA1125. Subjects will take one of two different doses of AXA1125 or a placebo twice daily, and a liver biopsy will be done at the beginning and end of the 48-week study.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Dose Ranging Study to Evaluate the Safety, Tolerability, and Efficacy of AXA1125 in Subjects With Non Cirrhotic, Non Alcoholic Steatohepatitis and Fibrosis (EMMPACT)

Conditions
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Non Alcoholic Steatohepatitis (NASH)

Intervention / Treatment
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* Drug: AXA1125
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing to participate in the study and provide written informed consent. Male and female adults aged > 18 years. Must have NASH and fibrosis on a liver biopsy sample If a historical liver biopsy is used for Screening, obtained within 6 months prior to Screening; Subjects may have a diagnosis of T2DM Exclusion Criteria: History or presence of liver disease (other than NAFLD or NASH) History or presence of cirrhosis and/or history or presence of hepatic decompensation

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AXA1125 22.6g<br>22.6 g AXA1125 administered orally BID with or without food | Drug: AXA1125<br>* AXA1125 administered BID with or without food<br>|
| Experimental: AXA1125 33.9g<br>33.9 g AXA1125 administered orally BID with or without food | Drug: AXA1125<br>* AXA1125 administered BID with or without food<br>|
| Placebo Comparator: Placebo<br>Matching Placebo administered orally BID with or without food | Drug: Placebo<br>* Matching Placebo administered BID with or without food<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in steatohepatitis | 2-point improvement from baseline to Week 48 in the non-alcoholic fatty liver disease (NAFLD) Activity Score (NAS) based on a scale from 0-8 with 0 being no NASH and 8 being the highest score | Baseline to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resolution of NASH without worsening of fibrosis | The proportion of subjects with resolution of NASH with no worsening of fibrosis defined as a post-treatment ballooning score of 0 and an inflammation score of 0 or 1 on liver biopsy. | Baseline to week 48 | 
| Improvement of fibrosis by one stage without worsening of NASH | The proportion of subjects who have at least a 1-stage improvement in fibrosis and no worsening of NASH based on liver biopsy 0 being no fibrosis and 4 being the worse. | Baseline to week 48 | 
| Incidence of study drug emergent adverse events (AEs) and serious adverse events (SAEs) |  | Baseline to week 48 | 
| Change from baseline in liver stiffness as measured by vibration controlled transient elastography (Fibroscan™) |  | Baseline to week 48 | 
| Change from baseline in hepatic fat as measured by MRI |  | Baseline to week 48 | 
| Change from baseline in measures of glucose control as determined by glycated hemoglobin (HbA1c) |  | Baseline to week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Steatosis, Lobular inflammation, Ballooning, Liver biopsy, Liver fat, Liver stiffness, NASH, Aminio Acids, Fibrosis