Efficacy and Safety of AXA1665 in Cirrhotic Subjects With Prior Overt Hepatic Encephalopathy

Study Overview
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Brief Summary
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This is a global study to compare the effects of AXA1665, an orally active mixture of amino acids, compared to placebo, on cognitive and physical function, as well as the safety and tolerability of AXA1665.

Official Title
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A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of AXA1665 in Subjects With Liver Cirrhosis and Prior Overt Hepatic Encephalopathy (EMMPOWER)

Conditions
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Hepatic Encephalopathy

Intervention / Treatment
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* Drug: AXA1665
* 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. History of cirrhosis and at least 1 prior episode of overt hepatic encephalopathy (OHE) prior to Screening. A PHES of ≤ -4 during Screening. MELD score of ≤ 22 at Screening. Support of a primary caregiver who is able and willing to give written informed consent. Exclusion Criteria: Hospitalization or serious medical condition. Presence of Child's-Pugh score ≥12, hepato-renal syndrome(s), refractory ascites, or spontaneous bacterial peritonitis (SBP). History of a surgical portosystemic or a transjugular intrahepatic portosystemic shunt (TIPS) placement. Expectation of a liver transplant during the study. Use of marijuana or tetrahydrocannabinol (THC) within 1 week prior to Screening and during the study.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AXA1665 53.8 g per day<br>AXA1665 administered orally TID | Drug: AXA1665<br>* AXA1665 administered TID with food<br>|
| Placebo Comparator: Matching placebo<br>Placebo administered orally TID | Drug: Placebo<br>* Matching placebo administered TID with food<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in neurocognitive function by Psychometric Hepatic Encephalopathy Score (PHES) |  | Baseline to week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to and frequency of recurrent overt hepatic encephalopathy |  | Baseline to week 24 | 
| Impact on physical function assessed by Liver Frailty Index (a composite measure of hand grip strength, balance and ability to stand up from a chair) |  | Baseline to week 24 | 
| Incidence of study product emergent adverse events (AEs) and serious adverse events (SAEs) |  | Baseline to week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver cirrhosis, end stage liver disease, sarcopenia, amino acids