Clinical trial NCT04073368: Study of the Safety and Tolerability of AXA1125 and AXA1957 in Subjects With Non-Alcoholic Fatty Liver Disease (NAFLD)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: NAFLD
Lead sponsor: Axcella Health, Inc
Sponsor class: INDUSTRY
First posted: 2019-08-29
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Subjects With Incidence of Study Product Emergent Adverse Events (AEs) and Any Serious Adverse Events (SAEs)
timeFrame: Baseline to week 16
Secondary outcomes:
measure: Percent Change in Liver Fat as Assessed by MRI- Proton Density Fat Fraction (PDFF)
timeFrame: Baseline to week 16
measure: Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)
timeFrame: Baseline to week 16
measure: Change in Glucose Homeostasis
timeFrame: Baseline to week 16
measure: Relative Change in Alanine Aminotransferase (ALT)
timeFrame: Baseline to week 16
measure: Change in Aspartate Aminotransferase (AST)
timeFrame: Baseline to Week 16
Other outcomes:
Locations:
city: Chandler
country: United States
facility: The Institute for Liver Health LLC
state: Arizona
city: Tucson
country: United States
facility: The Institute for Liver Health LLC
state: Arizona
city: Huntington Park
country: United States
facility: National Research Institute
state: California
city: Los Angeles
country: United States
facility: National Research Institute - Wilshire
state: California
city: Montclair
country: United States
facility: Catalina Research Institute, LLC
state: California
city: Panorama City
country: United States
facility: National Research Institute - Panorama
state: California
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials, LLC
state: Florida
city: Lakewood Ranch
country: United States
facility: Florida Digestive Health Specialists
state: Florida
city: Orlando
country: United States
facility: Compass Research, LLC - Orlando
state: Florida
city: Orlando
country: United States
facility: Bioclinica Research
state: Florida
city: Jackson
country: United States
facility: Southern Therapy and Advanced Research LLC
state: Mississippi
city: Kansas City
country: United States
facility: Kansas City Research Institute
state: Missouri
city: Germantown
country: United States
facility: Gastro One
state: Tennessee
city: Austin
country: United States
facility: Pinnacle Clinical Research
state: Texas
city: Dallas
country: United States
facility: Liver Center of Texas
state: Texas
city: Edinburg
country: United States
facility: Doctors Hospital at Renaissance, LLC
state: Texas
city: Fort Worth
country: United States
facility: Texas Digestive Disease Consultants (TDDC) - Downtown Fort Worth
state: Texas
city: San Antonio
country: United States
facility: Pinnacle Clinical Research
state: Texas
Study officials:
affiliation: Pinnacle Clinical Research
name: Stephen Harrison, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.