Study of the Safety and Tolerability of AXA1125 and AXA1957 in Subjects With Non-Alcoholic Fatty Liver Disease (NAFLD)

Study Overview
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Brief Summary
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This is a randomized, single blind study to determine whether AXA1125 or AXA1957, novel compositions of amino acids, are safe and well tolerated. Subjects have non-alcoholic fatty liver disease (NAFLD) and the study will also examine liver biology using blood tests and magnetic resonance imaging (MRI).

Detailed Description
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This was a 16-week, single-blind, randomized, placebo-controlled food study of the safety and tolerability of AXA1125 and AXA1957 in subjects with NAFLD. Subjects signed an informed consent form and were screened for eligibility, per the inclusion and exclusion criteria below, up to 6 weeks before the start of the administration period. Subjects were randomized as soon as eligibility was confirmed. Eligible subjects were randomized in a 2:2:2:1 ratio to receive either AXA1125 24 g twice daily (BID), AXA1957 20.3 g BID, AXA1957 13.5 g BID, or placebo 24 g BID. Randomization occurred via an interactive web response system after eligibility was confirmed and approximately 3 to 5 days prior to the Day 1 visit. Assigned study food product (AXA1125, AXA1957, or placebo) were shipped to the study site upon randomization of each subject. Once randomization had occurred, subjects presented to the study site on Day 1 (Baseline/Visit 2) for their baseline assessments per the schedule of events. Study Day 1 was the beginning of the 16-week administration period. Subjects returned to the study site at Week 1 (Visit 3), Week 2 (Visit 4), Week 4 (Visit 5), Week 8 (Visit 6), Week 12 (Visit 7), and Week 16 (Visit 8) to receive their study food product and/or to return any unused study food product, provide blood samples for biomarker and other laboratory testing, undergo liver imaging, and complete other study safety assessments per the schedule of events. The Safety Follow-up Visit, which occurred approximately 2 weeks after the last visit in the administration period (ie, after the Week 16 visit or at the time of early termination), was the End of Study Visit (Visit 9). There were 9 study visits in total, including the Screening and Follow-up Visits.

Official Title
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A 16-Week, Single-Blind Randomized, Placebo- Controlled Food Study of the Safety and Tolerability of AXA1125 and AXA1957 in Subjects With Non-Alcoholic Fatty Liver Disease (NAFLD)

Conditions
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NAFLD

Intervention / Treatment
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* Dietary Supplement: AXA1957
* Dietary Supplement: AXA1125
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Willing to participate in the study and provide written informed consent. Male and female adults aged > 18 years. Subjects must not have participated in any diet/lifestyle intervention or observational studies, or engaged in any body weight altering regimens that resulted in body weight fluctuations (i.e. body weight loss or gain by 5%) in the preceding 3 months prior to Screening. A screening MRI consistent with liver inflammation and fibrosis. Key Exclusion Criteria: Current or history of significant alcohol consumption. History or presence of liver disease (other than NAFLD/NASH). History or presence of cirrhosis and/or history or presence of hepatic decompensation. Any diabetes other than Type 2. Other poorly controlled medical condition (for example, uncontrolled hypertension with a systolic blood pressure > 100 mmHg). Known sensitivity and/or history of clinically significant food intolerance/allergies to proteins (including whey, soy, casein, amino acids, 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: AXA1957 high dose<br>AXA1957 20.3g | Dietary Supplement: AXA1957<br>* Amino acids, food study<br>|
| Active Comparator: AXA1957 low dose<br>AXA1957 13.5g | Dietary Supplement: AXA1957<br>* Amino acids, food study<br>|
| Active Comparator: AXA1125<br>AXA1125 24g | Dietary Supplement: AXA1125<br>* Amino acids, food study<br>|
| Placebo Comparator: Placebo<br>Placebo 24g | Dietary Supplement: Placebo<br>* Amino acids, food study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Incidence of Study Product Emergent Adverse Events (AEs) and Any Serious Adverse Events (SAEs) | Subjects received AXA1125 at 24 g twice daily ( BID), AXA1957 at 20.3 g BID or 13.5 g BID with Product related AEs and any SAEs up to 16 weeks | Baseline to week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Liver Fat as Assessed by MRI- Proton Density Fat Fraction (PDFF) | Relative Changes From Baseline in MRI-PDFF at Week 16 in Overall Subjects (Safety Analysis Population) | Baseline to week 16 | 
| Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) | Absolute Changes From Baseline in HOMA-IR at Week 16 in Overall Subjects (Safety Analysis Population) | Baseline to week 16 | 
| Change in Glucose Homeostasis | Absolute Changes From Baseline in HbA1c at Week 16 in Subjects with Diabetes (Safety Analysis Population) | Baseline to week 16 | 
| Relative Change in Alanine Aminotransferase (ALT) | Relative Changes From Baseline in ALT at Week 16 in Overall Subjects (Safety Analysis Population) | Baseline to week 16 | 
| Change in Aspartate Aminotransferase (AST) | Relative Changes From Baseline in AST at Week 16 in Overall Subjects (Safety Analysis Population) | Baseline to Week 16 |