Trial Outcomes & Findings for Study of the Safety and Tolerability of AXA1125 and AXA1957 in Subjects With Non-Alcoholic Fatty Liver Disease (NAFLD) (NCT NCT04073368)

NCT ID: NCT04073368

Last Updated: 2021-07-06

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 112 participants
• Primary outcome timeframe: Baseline to week 16
• Results posted on: 2021-07-06

Participant Flow

112 subjects signed consent and randomized. Ten subjects screen failed prior to day 1 dosing ( after signing consent) and the number of participants who started the study is 102 subjects.

Participant milestones

Measure	AXA1957 High Dose AXA1957 20.3g AXA1957: Amino acids, food study	AXA1957 Low Dose AXA1957 13.5g AXA1957: Amino acids, food study	AXA1125 AXA1125 24g AXA1125: Amino acids, food study	Placebo Placebo 24g Placebo: Amino acids, food study
Overall Study STARTED	32	26	29	15
Overall Study COMPLETED	20	18	26	13
Overall Study NOT COMPLETED	12	8	3	2

Reasons for withdrawal

Measure	AXA1957 High Dose AXA1957 20.3g AXA1957: Amino acids, food study	AXA1957 Low Dose AXA1957 13.5g AXA1957: Amino acids, food study	AXA1125 AXA1125 24g AXA1125: Amino acids, food study	Placebo Placebo 24g Placebo: Amino acids, food study
Overall Study Adverse Event	2	0	1	1
Overall Study Withdrawal by Subject	2	2	1	1
Overall Study Lost to Follow-up	1	1	1	0
Overall Study Protocol Violation	0	1	0	0
Overall Study Subject noncompliance	7	4	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	AXA1957 High Dose n=32 Participants AXA1957 20.3g AXA1957: Amino acids, food study	AXA1957 Low Dose n=26 Participants AXA1957 13.5g AXA1957: Amino acids, food study	AXA1125 n=29 Participants AXA1125 24g AXA1125: Amino acids, food study	Placebo n=15 Participants Placebo 24g Placebo: Amino acids, food study	Total n=102 Participants Total of all reporting groups
Age, Continuous	50.1 years STANDARD_DEVIATION 12.79 • n=5 Participants	49.6 years STANDARD_DEVIATION 10.74 • n=7 Participants	49.2 years STANDARD_DEVIATION 12.79 • n=5 Participants	53.2 years STANDARD_DEVIATION 9.62 • n=4 Participants	50.2 years STANDARD_DEVIATION 11.77 • n=21 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	16 Participants n=7 Participants	17 Participants n=5 Participants	10 Participants n=4 Participants	62 Participants n=21 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	10 Participants n=7 Participants	12 Participants n=5 Participants	5 Participants n=4 Participants	40 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) White	31 Participants n=5 Participants	24 Participants n=7 Participants	26 Participants n=5 Participants	14 Participants n=4 Participants	95 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	32 participants n=5 Participants	26 participants n=7 Participants	29 participants n=5 Participants	15 participants n=4 Participants	102 participants n=21 Participants
Type 2 diabetes mellitus status (T2DM)	12 Participants n=5 Participants	10 Participants n=7 Participants	12 Participants n=5 Participants	6 Participants n=4 Participants	40 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline to week 16

Population: Subjects received AXA1125 at 24 g BID, AXA1957 at 20.3 g BID or 13.5 g BID, or placebo for up to 16 weeks.

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

Outcome measures

Measure	AXA1957 High Dose n=32 Participants AXA1957 20.3g AXA1957: Amino acids, food study	AXA1957 Low Dose n=26 Participants AXA1957 13.5g AXA1957: Amino acids, food study	AXA1125 n=29 Participants AXA1125 24g AXA1125: Amino acids, food study	Placebo n=15 Participants Placebo 24g Placebo: Amino acids, food study
Number of Subjects With Incidence of Study Product Emergent Adverse Events (AEs) and Any Serious Adverse Events (SAEs) Any Product Related Product-Emergent AEs	10 participants	8 participants	13 participants	2 participants
Number of Subjects With Incidence of Study Product Emergent Adverse Events (AEs) and Any Serious Adverse Events (SAEs) Any SAEs	1 participants	0 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: Baseline to week 16

Population: Relative Changes From Baseline in MRI-PDFF at Week 16 in Overall Subjects (Safety Analysis Population)

Relative Changes From Baseline in MRI-PDFF at Week 16 in Overall Subjects (Safety Analysis Population)

Outcome measures

Measure	AXA1957 High Dose n=32 Participants AXA1957 20.3g AXA1957: Amino acids, food study	AXA1957 Low Dose n=26 Participants AXA1957 13.5g AXA1957: Amino acids, food study	AXA1125 n=29 Participants AXA1125 24g AXA1125: Amino acids, food study	Placebo n=15 Participants Placebo 24g Placebo: Amino acids, food study
Percent Change in Liver Fat as Assessed by MRI- Proton Density Fat Fraction (PDFF)	-8.12 percentage of change of MRI_PDFF Standard Deviation 24.904	-20.29 percentage of change of MRI_PDFF Standard Deviation 23.064	-22.88 percentage of change of MRI_PDFF Standard Deviation 23.040	-5.74 percentage of change of MRI_PDFF Standard Deviation 20.425

SECONDARY outcome

Timeframe: Baseline to week 16

Population: Absolute Changes From Baseline in HOMA-IR at Week 16 in Overall Subjects (Safety Analysis Population)

Absolute Changes From Baseline in HOMA-IR at Week 16 in Overall Subjects (Safety Analysis Population)

Outcome measures

Measure	AXA1957 High Dose n=32 Participants AXA1957 20.3g AXA1957: Amino acids, food study	AXA1957 Low Dose n=26 Participants AXA1957 13.5g AXA1957: Amino acids, food study	AXA1125 n=29 Participants AXA1125 24g AXA1125: Amino acids, food study	Placebo n=15 Participants Placebo 24g Placebo: Amino acids, food study
Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)	8.421 percentage of change of HOM-IR Standard Deviation 34.5866	1.445 percentage of change of HOM-IR Standard Deviation 3.6396	-4.369 percentage of change of HOM-IR Standard Deviation 16.8680	0.720 percentage of change of HOM-IR Standard Deviation 4.7074

SECONDARY outcome

Timeframe: Baseline to week 16

Population: Absolute Changes From Baseline in HbA1c at Week 16 in Subjects with Diabetes (Safety Analysis Population)

Absolute Changes From Baseline in HbA1c at Week 16 in Subjects with Diabetes (Safety Analysis Population)

Outcome measures

Measure	AXA1957 High Dose n=9 Participants AXA1957 20.3g AXA1957: Amino acids, food study	AXA1957 Low Dose n=9 Participants AXA1957 13.5g AXA1957: Amino acids, food study	AXA1125 n=11 Participants AXA1125 24g AXA1125: Amino acids, food study	Placebo n=3 Participants Placebo 24g Placebo: Amino acids, food study
Change in Glucose Homeostasis	0.0138 change in HbA1c Standard Deviation 0.01419	.0001 change in HbA1c Standard Deviation 0.00588	-0.0070 change in HbA1c Standard Deviation 8.008	-0.0027 change in HbA1c Standard Deviation 0.00874

SECONDARY outcome

Timeframe: Baseline to week 16

Population: Relative Changes From Baseline in ALT at Week 16 in Overall Subjects (Safety Analysis Population)

Relative Changes From Baseline in ALT at Week 16 in Overall Subjects (Safety Analysis Population)

Outcome measures

Measure	AXA1957 High Dose n=32 Participants AXA1957 20.3g AXA1957: Amino acids, food study	AXA1957 Low Dose n=26 Participants AXA1957 13.5g AXA1957: Amino acids, food study	AXA1125 n=29 Participants AXA1125 24g AXA1125: Amino acids, food study	Placebo n=15 Participants Placebo 24g Placebo: Amino acids, food study
Relative Change in Alanine Aminotransferase (ALT)	-20.65 percentage change of ALT Standard Deviation 30.163	-19.19 percentage change of ALT Standard Deviation 30.559	-21.86 percentage change of ALT Standard Deviation 25.991	-7.20 percentage change of ALT Standard Deviation 36.483

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Relative Changes From Baseline in AST at Week 16 in Overall Subjects (Safety Analysis Population)

Relative Changes From Baseline in AST at Week 16 in Overall Subjects (Safety Analysis Population)

Outcome measures

Measure	AXA1957 High Dose n=32 Participants AXA1957 20.3g AXA1957: Amino acids, food study	AXA1957 Low Dose n=26 Participants AXA1957 13.5g AXA1957: Amino acids, food study	AXA1125 n=29 Participants AXA1125 24g AXA1125: Amino acids, food study	Placebo n=15 Participants Placebo 24g Placebo: Amino acids, food study
Change in Aspartate Aminotransferase (AST)	-13.40 percentage of AST from basline Standard Deviation 30.898	-17.02 percentage of AST from basline Standard Deviation 30.898	-16.76 percentage of AST from basline Standard Deviation 27.908	-7.49 percentage of AST from basline Standard Deviation 40.499

Adverse Events

AXA1957 High Dose

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

AXA1957 Low Dose

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

AXA1125

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	AXA1957 High Dose n=32 participants at risk AXA1957 20.3g AXA1957: Amino acids, food study	AXA1957 Low Dose n=26 participants at risk AXA1957 13.5g AXA1957: Amino acids, food study	AXA1125 n=29 participants at risk AXA1125 24g AXA1125: Amino acids, food study	Placebo n=15 participants at risk Placebo 24g Placebo: Amino acids, food study
Renal and urinary disorders nephrolithiasis	0.00% 0/32 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	0.00% 0/26 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	3.4% 1/29 • Number of events 2 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	0.00% 0/15 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs
Neoplasms benign, malignant and unspecified (incl cysts and polyps) laryngeal squamous cell carcinoma	3.1% 1/32 • Number of events 1 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	0.00% 0/26 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	0.00% 0/29 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	0.00% 0/15 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs

Other adverse events

Measure	AXA1957 High Dose n=32 participants at risk AXA1957 20.3g AXA1957: Amino acids, food study	AXA1957 Low Dose n=26 participants at risk AXA1957 13.5g AXA1957: Amino acids, food study	AXA1125 n=29 participants at risk AXA1125 24g AXA1125: Amino acids, food study	Placebo n=15 participants at risk Placebo 24g Placebo: Amino acids, food study
Gastrointestinal disorders Diarrhoea	18.8% 6/32 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	11.5% 3/26 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	34.5% 10/29 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	6.7% 1/15 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs
Gastrointestinal disorders Nausea	9.4% 3/32 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	11.5% 3/26 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	13.8% 4/29 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	6.7% 1/15 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs
Infections and infestations Upper respiratory tract infection	6.2% 2/32 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	0.00% 0/26 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	13.8% 4/29 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	6.7% 1/15 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs
Metabolism and nutrition disorders Decreased appetite	3.1% 1/32 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	7.7% 2/26 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	10.3% 3/29 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	0.00% 0/15 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs
Nervous system disorders Headache	6.2% 2/32 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	15.4% 4/26 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	3.4% 1/29 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs	6.7% 1/15 • From the time of informed consent up to first administration of study product on Day 1, any untoward medical occurrence considered related to study procedures will be recorded as an AE. Adverse events that occur from the first administration of study product on Day 1 through the Follow-up Visit / Week 18 will be considered treatment-emergent AEs

Additional Information

Margaret Koziel, MD

Axcella Health, Inc

Phone: 8573202200

Email: clinicaltrials@axcellahealth.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place