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

Not Applicable

Completed

• Conditions: NAFLD
• Interventions: Dietary Supplement: Placebo; Dietary Supplement: AXA1957; Dietary Supplement: AXA1125

• Registration Number: NCT04073368
• Lead Sponsor: Axcella Health, Inc

Brief Summary

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

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 Timeline

• Study Start: 2018-12-03
• Study First Submitted: 2019-08-27
• Study First Submitted QC: 2019-08-27
• Study First Posted: 2019-08-29
• Primary Completion: 2020-03-31
• Study Completion: 2020-09-03
• Status Verified: 2021-06
• Results First Submitted: 2021-06-08
• Results First Submitted QC: 2021-06-30
• Last Update Submitted: 2021-07-01
• Results First Posted: 2021-07-02
• Last Update Posted: 2021-07-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 112

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo 24g
AXA1957 low dose	AXA1957	AXA1957 13.5g
AXA1125	AXA1125	AXA1125 24g
AXA1957 high dose	AXA1957	AXA1957 20.3g

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Incidence of Study Product Emergent Adverse Events (AEs) and Any Serious Adverse Events (SAEs)	Baseline to week 16	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

Secondary Outcome Measures

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

Trial Locations

Locations (16)

Pinnacle Clinical Research; 🇺🇸 San Antonio, Texas, United States

National Research Institute - Wilshire; 🇺🇸 Los Angeles, California, United States

National Research Institute; 🇺🇸 Huntington Park, California, United States

Catalina Research Institute, LLC; 🇺🇸 Montclair, California, United States

Excel Medical Clinical Trials, LLC; 🇺🇸 Boca Raton, Florida, United States

Florida Digestive Health Specialists; 🇺🇸 Lakewood Ranch, Florida, United States

Bioclinica Research; 🇺🇸 Orlando, Florida, United States

Compass Research, LLC - Orlando; 🇺🇸 Orlando, Florida, United States

Kansas City Research Institute; 🇺🇸 Kansas City, Missouri, United States

Liver Center of Texas; 🇺🇸 Dallas, Texas, United States

Doctors Hospital at Renaissance, LLC; 🇺🇸 Edinburg, Texas, United States

Texas Digestive Disease Consultants (TDDC) - Downtown Fort Worth; 🇺🇸 Fort Worth, Texas, United States

Southern Therapy and Advanced Research LLC; 🇺🇸 Jackson, Mississippi, United States

Gastro One; 🇺🇸 Germantown, Tennessee, United States

The Institute for Liver Health LLC; 🇺🇸 Tucson, Arizona, United States

National Research Institute - Panorama; 🇺🇸 Panorama City, California, United States