Trial Outcomes & Findings for Study to Assess the Safety and Biological Activity of AMX0035 for the Treatment of Alzheimer's Disease (NCT NCT03533257)

NCT ID: NCT03533257

Last Updated: 2025-03-07

Results Overview

Comparison between the AMX0035 Group and Placebo of the number of participants with TEAEs

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

95 participants

Primary outcome timeframe

From first dose to 24 weeks

Results posted on

2025-03-07

Participant Flow

Participant milestones

Participant milestones
Measure	Active (AMX0035) AMX0035 twice daily--a combination of Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO)	Placebo Taste-matched Placebo Placebo: Placebo
Overall Study STARTED	51	44
Overall Study COMPLETED	41	42
Overall Study NOT COMPLETED	10	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Active (AMX0035) AMX0035 twice daily--a combination of Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO)	Placebo Taste-matched Placebo Placebo: Placebo
Overall Study Adverse Event	4	2
Overall Study Enrolled in other study, terminated by Sponsor, other	6	0

Baseline Characteristics

Study to Assess the Safety and Biological Activity of AMX0035 for the Treatment of Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active (AMX0035) n=51 Participants AMX0035 twice daily--a combination of Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO)	Placebo n=44 Participants Taste-matched Placebo	Total n=95 Participants Total of all reporting groups
Age, Continuous	70.7 years STANDARD_DEVIATION 7.69 • n=5 Participants	70.7 years STANDARD_DEVIATION 7.30 • n=7 Participants	70.7 years STANDARD_DEVIATION 7.48 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	19 Participants n=7 Participants	43 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	25 Participants n=7 Participants	52 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 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
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	49 Participants n=5 Participants	43 Participants n=7 Participants	92 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	51 participants n=5 Participants	44 participants n=7 Participants	95 participants n=5 Participants
ApoE4 Gene Group 1 Carrier	37 Participants n=5 Participants	27 Participants n=7 Participants	64 Participants n=5 Participants
ApoE4 Gene Group 1 Non-carrier	11 Participants n=5 Participants	17 Participants n=7 Participants	28 Participants n=5 Participants
ApoE4 Gene Group 1 Not reported	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
ApeE4 Gene Group 2 1 allele	29 Participants n=5 Participants	18 Participants n=7 Participants	47 Participants n=5 Participants
ApeE4 Gene Group 2 2 alleles	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
ApeE4 Gene Group 2 Non-carrier	11 Participants n=5 Participants	17 Participants n=7 Participants	28 Participants n=5 Participants
ApeE4 Gene Group 2 Not reported	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: From first dose to 24 weeks

Population: Safety Population

Comparison between the AMX0035 Group and Placebo of the number of participants with TEAEs

Outcome measures

Outcome measures
Measure	Active (AMX0035) n=51 Participants AMX0035 twice daily--a combination of Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO)	Placebo n=44 Participants Taste-matched Placebo
Number of Participants With Treatment-Emergent Adverse Event (TEAEs)	34 Participants	26 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: ITT population

Change from Baseline in GST (global statistical test combining three measures relevant to disease trajectory (cognition \[MADCOMS: Mild/Moderate Alzheimer's Disease Composite Score\], function \[FAQ: Functional Activities Questionnaire\], and total hippocampal volume on magnetic resonance imaging)) for AMX0035 relative to placebo. For MADCOMS and FAQ, a higher score indicates a worse outcome. A larger hippocampal volume is better, so it was reversed before being normalized. Each of the three were normalized against respective baseline means and standard deviations. The mean of the three normalized scores is the final GST. A higher GST score indicates a worse outcome. Standard deviations above the mean are worse; standard deviations below the mean are better. The expected value of the GST at baseline is 0 because it is the mean of three z-scores whose expected values at baseline are 0. AD is multifaceted and the GST was designed to be sensitive to changes in multiple dimensions.

Outcome measures

Outcome measures
Measure	Active (AMX0035) n=51 Participants AMX0035 twice daily--a combination of Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO)	Placebo n=44 Participants Taste-matched Placebo
Effect of Treatment on a Global Composite Statistical Test of Cognition, Function, and Neuroanatomy (GST)	0.24 score on a scale Standard Error 0.049	0.17 score on a scale Standard Error 0.052

SECONDARY outcome

Timeframe: 24 weeks

Population: ITT population

Impact of AMX0035 on clinical symptoms as measured by Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog). Scoring is in the range of 0 to 90 with a higher score indicating greater cognitive impairment.

Outcome measures

Outcome measures
Measure	Active (AMX0035) n=51 Participants AMX0035 twice daily--a combination of Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO)	Placebo n=44 Participants Taste-matched Placebo
Effect of Treatment on Cognition	2.26 score on a scale Standard Error 1.402	1.52 score on a scale Standard Error 1.496

SECONDARY outcome

Timeframe: 24 weeks

Population: ITT population

Impact of AMX0035 on Functional Activities Questionnaire (FAQ) scores. FAQ total score can range from 0 to 30, with higher scores indicating less functional independence.

Outcome measures

Outcome measures
Measure	Active (AMX0035) n=51 Participants AMX0035 twice daily--a combination of Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO)	Placebo n=44 Participants Taste-matched Placebo
Effect of Treatment on Functioning	2.61 score on a scale Standard Error 0.790	1.59 score on a scale Standard Error 0.845

SECONDARY outcome

Timeframe: 24 weeks

Population: ITT population

Impact of AMX0035 on Dementia Severity Rating Scale (DSRS) scores. Total score can range from 0 to 54, with higher scores indicating greater severity of dementia.

Outcome measures

Outcome measures
Measure	Active (AMX0035) n=51 Participants AMX0035 twice daily--a combination of Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO)	Placebo n=44 Participants Taste-matched Placebo
Effect of Treatment on Dementia Severity	2.34 score on a scale Standard Error 0.595	1.81 score on a scale Standard Error 0.636

SECONDARY outcome

Timeframe: 24 weeks

Population: ITT population

Impact of AMX0035 on the Montreal Cognitive Assessment (MoCA) scores. MoCA scores can range from 0 to 30, with lower scores indicating greater cognitive impairment.

Outcome measures

Outcome measures
Measure	Active (AMX0035) n=51 Participants AMX0035 twice daily--a combination of Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO)	Placebo n=44 Participants Taste-matched Placebo
Effect of Treatment on Cognitive Impairment	-2.18 score on a scale Standard Error 0.483	-0.70 score on a scale Standard Error 0.512

SECONDARY outcome

Timeframe: 24 weeks

Population: ITT population

Impact of AMX0035 on neuropsychiatric symptoms as assessed by the Neuropsychiatric Inventory (NPI). The total score ranges from 0 to 36, with higher scores indicating a greater severity of symptoms.

Outcome measures

Outcome measures
Measure	Active (AMX0035) n=51 Participants AMX0035 twice daily--a combination of Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO)	Placebo n=44 Participants Taste-matched Placebo
Effect of Treatment on Neuropsychiatric Symptoms	0.15 score on a scale Standard Error 0.490	-0.46 score on a scale Standard Error 0.526

SECONDARY outcome

Timeframe: 24 weeks

Population: ITT population

Impact of AMX0035 on levels of hippocampal atrophy, as assessed by volumetric Magnetic Resonance Imaging (vMRI)

Outcome measures

Outcome measures
Measure	Active (AMX0035) n=51 Participants AMX0035 twice daily--a combination of Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO)	Placebo n=44 Participants Taste-matched Placebo
Regional Brain Volume	-75.18 mm^3 Standard Error 25.429	-70.78 mm^3 Standard Error 23.308

Adverse Events

Active (AMX0035)

Serious events: 3 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Active (AMX0035) n=51 participants at risk AMX0035--a combination of Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO)	Placebo n=44 participants at risk Taste-matched Placebo
Psychiatric disorders Depression	2.0% 1/51 • Number of events 1 • 24 weeks	0.00% 0/44 • 24 weeks
Injury, poisoning and procedural complications Burns third degree	2.0% 1/51 • Number of events 1 • 24 weeks	0.00% 0/44 • 24 weeks
Infections and infestations Pneumonia viral	2.0% 1/51 • Number of events 1 • 24 weeks	0.00% 0/44 • 24 weeks
Nervous system disorders Cerebral infarction	0.00% 0/51 • 24 weeks	2.3% 1/44 • Number of events 1 • 24 weeks

Other adverse events

Other adverse events
Measure	Active (AMX0035) n=51 participants at risk AMX0035--a combination of Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO)	Placebo n=44 participants at risk Taste-matched Placebo
Gastrointestinal disorders Diarrhoea	15.7% 8/51 • 24 weeks	6.8% 3/44 • 24 weeks
Nervous system disorders Headache	7.8% 4/51 • 24 weeks	11.4% 5/44 • 24 weeks

Additional Information

Chief Medical Officer

Amylyx Pharmaceuticals, Inc.

Phone: (877) 374-1208

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place