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| Name | Class |
|---|---|
| Alzheimer's Drug Discovery Foundation | OTHER |
| Alzheimer's Association | OTHER |
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The study is a 24-week, randomized, double-blind, multi-site, placebo-controlled study in participants with mild cognitive impairment (MCI) or early dementia due to Alzheimer's disease (AD).
The study is a 24-week, randomized, double-blind, multi-site, placebo-controlled study in participants with mild cognitive impairment (MCI) or early dementia due to Alzheimer's disease (AD). The study is designed to evaluate the safety, tolerability, drug target engagement and neurobiological effects of treatment with AMX0035 over 24 weeks. The study is designed to yield deep phenotyping insight for the purposes of demonstrating the effects of AMX0035 on mechanistic targets of engagement and disease biology. The study will evaluate diverse disease-relevant markers and produce an informative dataset that will allow for evaluation and correlation of imaging-based markers, neurobiological changes, functional measures, and cognitive outcomes. Participants receive orally administered study drug twice daily for a treatment duration of approximately 24 weeks and attend clinic visits at Screening, Baseline, Week 6, Week 12, Week 18, and Week 24.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active (AMX0035) | Active Comparator | AMX0035 twice daily--a combination of Sodium Phenylbutyrate (3g) and Taurursodiol (1g) |
|
| Placebo | Placebo Comparator | Taste-matched Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AMX0035 | Drug | Combination Therapy of PB and TURSO |
|
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Event (TEAEs) | Comparison between the AMX0035 Group and Placebo of the number of participants with TEAEs | From first dose to 24 weeks |
| Effect of Treatment on a Global Composite Statistical Test of Cognition, Function, and Neuroanatomy (GST) | 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. | 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of Treatment on Cognition | 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. | 24 weeks |
| Effect of Treatment on Functioning |
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Inclusion Criteria:
Exclusion Criteria:
Any CNS disease other than suspected AD, such as clinical stroke, brain tumor, normal pressure hydrocephalus, multiple sclerosis, significant head trauma with persistent neurological cognitive deficits or complaints, Parkinson's disease, frontotemporal dementia, or other neurodegenerative diseases
Abnormal liver function defined as AST and/or ALT > 3 times the upper limit of normal
Renal insufficiency as defined by a serum creatinine > 1.5 times the upper limit of normal
Recent (less than 1 year) cholecystectomy or the presence of post-cholecystectomy syndrome or biliary obstruction
Clinically significant unstable medical condition (other than AD) that in the Site Investigator opinion would pose a risk to the participant if they were to participate in the study
Any contraindication to undergo MRI studies such as:
MRI findings that show one or more of the following:
Major active or chronic psychiatric illness (e.g. depression, bipolar disorder, obsessive compulsive disorder, schizophrenia) that is not stable or well controlled within the previous year prior to baseline
Any significant neurodevelopmental disability
Current suicidal ideation or history of suicide attempt within 5 years of baseline or significant change from the screening and baseline C-SSRS at the discretion of the Site Investigator
History of alcohol or other substance abuse or dependence within the past 2 years
Any significant systemic illness or medical condition that could affect safety or compliance with study at the discretion of the Site Investigator
Laboratory abnormalities in B12, TSH, or other common laboratory parameters that might contribute to cognitive dysfunction
Current use of medications with psychoactive properties that may deleteriously affect cognition (e.g., anticholinergics, centrally-acting antihistamines, antipsychotics, sedative hypnotics, anxiolytics)
Use of any investigational therapy being used or evaluated for the treatment of AD is prohibited beginning 3 months (90 days) prior to the Baseline Visit and throughout the study.
Use of other investigational agents 1 month (28 days) prior to the Baseline Visit and for the duration of the trial.
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| Name | Affiliation | Role |
|---|---|---|
| Patrick Yeramian, MD | Amylyx Pharmaceuticals Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Neuroscience Solutions, Inc. - Jacksonville | Jacksonville | Florida | 32256 | United States | ||
| Clinical Neuroscience Solutions, Inc. - Orlando |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39131742 | Result | Arnold SE, Hendrix S, Nicodemus-Johnson J, Knowlton N, Williams VJ, Burns JM, Crane M, McManus AJ, Vaishnavi SN, Arvanitakis Z, Neugroschl J, Bell K, Trombetta BA, Carlyle BC, Kivisakk P, Dodge HH, Tanzi RE, Yeramian PD, Leslie K. Biological effects of sodium phenylbutyrate and taurursodiol in Alzheimer's disease. Alzheimers Dement (N Y). 2024 Aug 9;10(3):e12487. doi: 10.1002/trc2.12487. eCollection 2024 Jul-Sep. | |
| 37941072 |
| Label | URL |
|---|---|
| "Biological effects of sodium phenylbutyrate and taurursodiol in Alzheimer's disease" | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Active (AMX0035) | AMX0035 twice daily--a combination of Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO) |
| FG001 | Placebo | Taste-matched Placebo Placebo: Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 10, 2020 | Jul 22, 2024 |
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Placebo-Controlled, Double-Blind, Parallel-Group
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| Placebo | Drug | Placebo |
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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. |
| 24 weeks |
| Effect of Treatment on Dementia Severity | 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. | 24 weeks |
| Effect of Treatment on Cognitive Impairment | 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. | 24 weeks |
| Effect of Treatment on Neuropsychiatric Symptoms | 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. | 24 weeks |
| Regional Brain Volume | Impact of AMX0035 on levels of hippocampal atrophy, as assessed by volumetric Magnetic Resonance Imaging (vMRI) | 24 weeks |
| Orlando |
| Florida |
| 32801 |
| United States |
| International Medical Investigational Centers (IMIC) | Palmetto Bay | Florida | 33157 | United States |
| Rush University Medical Center | Chicago | Illinois | 60612 | United States |
| University of Kansas Clinical Research Center | Fairway | Kansas | 66205 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Rowan University School of Osteopathic Medicine | Stratford | New Jersey | 08084 | United States |
| Mount Sinai Alzheimer's Disease Research Center | New York | New York | 10029 | United States |
| Columbia University | New York | New York | 10032 | United States |
| Hospital of the University of Pennsylvania, Penn Memory Center | Philadelphia | Pennsylvania | 19104 | United States |
| Genesis NeuroScience Clinic | Knoxville | Tennessee | 37909 | United States |
| Derived |
| Wen ZQ, Lin J, Xie WQ, Shan YH, Zhen GH, Li YS. Insights into the underlying pathogenesis and therapeutic potential of endoplasmic reticulum stress in degenerative musculoskeletal diseases. Mil Med Res. 2023 Nov 9;10(1):54. doi: 10.1186/s40779-023-00485-5. |
| COMPLETED |
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| NOT COMPLETED |
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Safety Population
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| ID | Title | Description |
|---|---|---|
| BG000 | Active (AMX0035) | AMX0035 twice daily--a combination of Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO) |
| BG001 | Placebo | Taste-matched Placebo |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| ApoE4 Gene Group 1 | Count of Participants | Participants |
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| ApeE4 Gene Group 2 | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment-Emergent Adverse Event (TEAEs) | Comparison between the AMX0035 Group and Placebo of the number of participants with TEAEs | Safety Population | Posted | Count of Participants | Participants | From first dose to 24 weeks |
|
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| |||||||||||||||||||||||||||||
| Primary | Effect of Treatment on a Global Composite Statistical Test of Cognition, Function, and Neuroanatomy (GST) | 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. | ITT population | Posted | Least Squares Mean | Standard Error | score on a scale | 24 weeks |
| ||||||||||||||||||||||||||||||
| Secondary | Effect of Treatment on Cognition | 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. | ITT population | Posted | Least Squares Mean | Standard Error | score on a scale | 24 weeks |
|
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| Secondary | Effect of Treatment on Functioning | 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. | ITT population | Posted | Least Squares Mean | Standard Error | score on a scale | 24 weeks |
|
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| Secondary | Effect of Treatment on Dementia Severity | 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. | ITT population | Posted | Least Squares Mean | Standard Error | score on a scale | 24 weeks |
|
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| Secondary | Effect of Treatment on Cognitive Impairment | 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. | ITT population | Posted | Least Squares Mean | Standard Error | score on a scale | 24 weeks |
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| Secondary | Effect of Treatment on Neuropsychiatric Symptoms | 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. | ITT population | Posted | Least Squares Mean | Standard Error | score on a scale | 24 weeks |
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| Secondary | Regional Brain Volume | Impact of AMX0035 on levels of hippocampal atrophy, as assessed by volumetric Magnetic Resonance Imaging (vMRI) | ITT population | Posted | Least Squares Mean | Standard Error | mm^3 | 24 weeks |
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24 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Active (AMX0035) | AMX0035--a combination of Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO) | 0 | 51 | 3 | 51 | 12 | 51 |
| EG001 | Placebo | Taste-matched Placebo | 0 | 44 | 1 | 44 | 6 | 44 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Depression | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Burns third degree | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Pneumonia viral | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Cerebral infarction | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Amylyx Pharmaceuticals, Inc. | (877) 374-1208 | medinfo@amylyx.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 8, 2020 | Jul 22, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C000723627 | sodium phenylbutyrate and taurursodiol |
| C075773 | 4-phenylbutyric acid |
| C031655 | ursodoxicoltaurine |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Non-carrier |
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| Not reported |
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| 2 alleles |
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| Non-carrier |
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| Not reported |
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