Study of the Safety and Tolerability of AXA1665 in Subjects With Mild and Moderate Hepatic Insufficiency

Study Overview
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Brief Summary
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This is a randomized, single blind study to determine whether AXA1665, a composition of naturally occuring amino acids, is well tolerated in subjects with mild and moderate hepatic insufficiency. Study will also examine how the food product may influence the biology in muscle which will be assessed using magnetic resonance imaging (MRI) and other functional assessments such as strength, balance and cognition as part of a comprehensive physical/neurological exam. Changes in blood biomarkers of inflammation will also be assessed.

Official Title
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A 12-Week, Single-Blind, Placebo-Controlled, Randomized Study to Evaluate the Safety, Tolerability, and Physiological Regulation of an Amino Acid Food Product, AXA1665, in Subjects With Mild and Moderate Hepatic Insufficiency

Conditions
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Hepatic Insufficiency

Intervention / Treatment
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* Dietary Supplement: AXA1665
* Dietary Supplement: 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 Child-Pugh score ≤9 (i.e. Child-Pugh class A or B) Liver Frailty Index (LFI) of ≥3.6 Willing and able to engage in 30 minutes of walking/physical activity at least 3 days per week Exclusion Criteria: Hospitalization for any complication of cirrhosis or taking new medications intended to treat hepatic encephalopathy within 2 months prior to Screening or any hospitalization for any cause/reason within 30 days prior to Screening Prior history or presence of a transjugular intrahepatic portal systemic shunt (TIPS) Current or history of significant alcohol consumption Other poorly controlled medical condition [e.g., renal disease with an estimated glomerular filtration rate (GFR) <60 mL/min/1.73m2) Known sensitivity and/or history of clinically significant food intolerance/allergies to proteins (including whey, soy, casein, amino acids, etc.) Any extreme or unbalanced diet such as Ketogenic, Atkins, Paleo, Vegan, etc. Unable or unwilling to adhere to contraception requirements Any contraindications to a MRI scan Any other condition that, in the opinion of the Investigator, renders the subject at risk for compliance, compromises the well-being of the subject, or hinders study completion

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AXA1665 29.4g<br>Dietary Supplement: AXA1665 Amino acids, food study | Dietary Supplement: AXA1665<br>* Dietary supplement: AXA1665<br>|
| Active Comparator: AXA1665 53.9 g<br>Dietary Supplement: AXA1665 Amino acids, food study | Dietary Supplement: AXA1665<br>* Dietary supplement: AXA1665<br>|
| Placebo Comparator: Placebo 29.4 g<br>Dietary Supplement: Placebo | Dietary Supplement: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of study product emergent adverse events (AEs) and serious adverse events (SAEs) |  | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in muscle mass by MRI |  | Baseline to Week 12 | 
| Change in Fischer's ratio [measured by ratio of branched-chain amino acids (leucine, valine, isoleucine) to aromatic amino acids (phenylalanine, tyrosine)] |  | Baseline to Week 12 | 
| Change in plasma ammonia |  | Baseline to Week 12 | 
| Change in blood urea nitrogen concentration |  | Baseline to Week 12 | 
| Change in creatinine concentration |  | Baseline to Week 12 | 
| Change in gait speed |  | Baseline to Week 12 | 
| Change in Liver Frailty Index |  | Baseline to Week 12 | 
| Change in overall physical activity (measured by actigraphy watch) |  | Baseline to Week 12 | 
| Change in cognitive function measured by the Psychometric Hepatic Encephalopathy Score (PHES) |  | Baseline to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amino acids, food study