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

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)

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).

Study Overview

• Status: Completed
• Conditions: NAFLD
• Intervention / Treatment: Dietary supplement: AXA1957; Dietary supplement: AXA1125; Dietary supplement: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • The Institute for Liver Health LLC
    • Tucson, Arizona, United States, 85641
      • The Institute for Liver Health LLC
  • California
    • Huntington Park, California, United States, 90255
      • National Research Institute
    • Los Angeles, California, United States, 90010
      • National Research Institute - Wilshire
    • Montclair, California, United States, 91762
      • Catalina Research Institute, LLC
    • Panorama City, California, United States, 91402
      • National Research Institute - Panorama
  • Florida
    • Boca Raton, Florida, United States, 33427
      • Excel Medical Clinical Trials, LLC
    • Lakewood Ranch, Florida, United States, 34202
      • Florida Digestive Health Specialists
    • Orlando, Florida, United States, 32806
      • Bioclinica Research
    • Orlando, Florida, United States, 32789
      • Compass Research, LLC - Orlando
  • Mississippi
    • Jackson, Mississippi, United States, 39056
      • Southern Therapy and Advanced Research LLC
  • Missouri
    • Kansas City, Missouri, United States, 64030
      • Kansas City Research Institute
  • Tennessee
    • Germantown, Tennessee, United States, 20874
      • Gastro One
  • Texas
    • Austin, Texas, United States, 73301
      • Pinnacle Clinical Research
    • Dallas, Texas, United States, 75234
      • Liver Center of Texas
    • Edinburg, Texas, United States, 78504
      • Doctors Hospital at Renaissance, LLC
    • Fort Worth, Texas, United States, 76104
      • Texas Digestive Disease Consultants (TDDC) - Downtown Fort Worth
    • San Antonio, Texas, United States, 78201
      • Pinnacle Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: AXA1957 high dose; AXA1957 20.3g	Dietary supplement: AXA1957; Amino acids, food study
Active Comparator: AXA1957 low dose; AXA1957 13.5g	Dietary supplement: AXA1957; Amino acids, food study
Active Comparator: AXA1125; AXA1125 24g	Dietary supplement: AXA1125; Amino acids, food study
Placebo Comparator: Placebo; Placebo 24g	Dietary supplement: Placebo; Amino acids, food study

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Axcella Health, Inc
• Investigators: Principal Investigator: Stephen Harrison, MD, Pinnacle Clinical Research

Publications and helpful links

General Publications

• Harrison SA, Baum SJ, Gunn NT, Younes ZH, Kohli A, Patil R, Koziel MJ, Chera H, Zhao J, Chakravarthy MV. Safety, Tolerability, and Biologic Activity of AXA1125 and AXA1957 in Subjects With Nonalcoholic Fatty Liver Disease. Am J Gastroenterol. 2021 Dec 1;116(12):2399-2409. doi: 10.14309/ajg.0000000000001375.

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2018
• Primary Completion (Actual): March 31, 2020
• Study Completion (Actual): September 3, 2020

Study Registration Dates

• First Submitted: August 27, 2019
• First Submitted That Met QC Criteria: August 27, 2019
• First Posted (Actual): August 29, 2019

Study Record Updates

• Last Update Posted (Actual): July 6, 2021
• Last Update Submitted That Met QC Criteria: July 1, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: AXA1125-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No