Alzheimer DiseasePhase 2PEGASUSNCT03533257
Study to Assess the Safety and Biological Activity of AMX0035 for the Treatment of Alzheimer's Disease
A Phase 2 study testing AMX0035 in people with Alzheimer Disease, run by Amylyx Pharmaceuticals Inc. at 11 sites in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 55 to 89 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- AMX0035
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 95 participants
- Where
- 11 sitesUnited States
- Study dates
- 14 Sep 2018to 6 Nov 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ages 55-89, inclusive, male or female
- Diagnosis of "Probable Alzheimer's Disease" or Mild Cognitive Impairment (amnestic or amnestic plus other) with biomarkers that suggest intermediate or high likelihood that the syndrome is due to AD, according to 2011 NIA-AA Workgroup criteria
- MoCA score >/=8
- Able to read and write in English sufficiently to complete all study procedures
- Geriatric Depression Scale <7
- Willing and able to complete all assessments and study procedures
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- Not pregnant, lactating or of child-bearing potential (women must be >2 years post-menopausal or surgically sterile)
- Study partner with at least two days per week with contact with patient willing to accompany patient to visits and complete partner study forms
- No known hypersensitivity to TURSO or Phenylbutyrate
- If on cholinesterase inhibitor and/or memantine, treatment must have started for no less than 3 months (84 days) prior to baseline and the dosing regimen must have remained stable for 6 weeks (42 days) prior to baseline. The Investigator anticipated that the dosing regimen at baseline would remain unchanged throughout participation in the study.
Who cannot join
- 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:
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- History of a cardiac pacemaker or pacemaker wires
- Metallic particles in the body
- Vascular clips in the head
- Prosthetic heart valves
- Severe claustrophobia impeding ability to participate in an imaging study, or
- MRI findings that show one or more of the following:
- More than 4 incidental microhemorrhages
- Incidental lacunar infarct with attributable signs or symptoms and with history of stroke
- Incidental meningiomas with attributable signs or symptoms
- Newly recognized meningioma
- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Rush University Medical Center
Chicago, Illinois, 60612
University of Kansas Clinical Research Center
Fairway, Kansas, 66205
Clinical Neuroscience Solutions, Inc. - Jacksonville
Jacksonville, Florida, 32256
Genesis NeuroScience Clinic
Knoxville, Tennessee, 37909
Mount Sinai Alzheimer's Disease Research Center
New York, New York, 10029
Columbia University
New York, New York, 10032
Clinical Neuroscience Solutions, Inc. - Orlando
Orlando, Florida, 32801
International Medical Investigational Centers (IMIC)
Palmetto Bay, Florida, 33157
Hospital of the University of Pennsylvania, Penn Memory Center
Philadelphia, Pennsylvania, 19104
Rowan University School of Osteopathic Medicine
Stratford, New Jersey, 08084
About this study
Official title: Phase II Study to Assess the Safety, Tolerability, and Target Engagement of AMX0035, a Fixed Combination of Sodium Phenylbutyrate and Tauroursodeoxycholic Acid for the Treatment of Alzheimer's Disease
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).
Read the detailed description
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.
- Conditions
- Alzheimer Disease
- Being tested
- AMX0035, Placebo
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMX0035Drug
Also called Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO; also known as Tauroursodeoxycholic Acid [TUDCA])
Combination Therapy of PB and TURSO
PlaceboDrug
Also called Comparator
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Active (AMX0035) | Active comparator | AMX0035 twice daily--a combination of Sodium Phenylbutyrate (3g) and Taurursodiol (1g) Receives: Drug: AMX0035 |
| Placebo | Placebo comparator | Taste-matched Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Emergent Adverse Event (TEAEs)
Comparison between the AMX0035 Group and Placebo of the number of participants with TEAEs
Measured: 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.
Measured: 24 weeks
Secondary outcomes (6)
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.
Measured: 24 weeks
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 24 weeks
Regional Brain Volume
Impact of AMX0035 on levels of hippocampal atrophy, as assessed by volumetric Magnetic Resonance Imaging (vMRI)
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2018
- Study start14 Sep 2018
- Primary completion22 Oct 2020
- Study completion6 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Placebo-Controlled, Double-Blind, Parallel-Group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amylyx Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Alzheimer's Drug Discovery Foundation, Alzheimer's Association
- Responsible party
- Sponsor
- Investigators
- Patrick Yeramian, MD, Study director, Amylyx Pharmaceuticals Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03533257
- Sponsor's protocol ID
- AMX-8000
- Acronym
- PEGASUS
- Status last verified
- Mar 2025
- First submitted
- 30 Apr 2018
- Last updated
- 7 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39131742Wen 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.
PubMed 37941072
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study to Assess the Safety, Tolerability, and Target Engagement of AMX0035, a Fixed Combination of Sodium Phenylbutyrate and Tauroursodeoxycholic Acid for the Treatment of Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT03533257
- Acronym / sponsor ID
- PEGASUS / AMX-8000
- Conditions
- Alzheimer Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 95 participants (actual)
- Lead sponsor
- Amylyx Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Collaborators
- Alzheimer's Drug Discovery Foundation, Alzheimer's Association
- Study start
- 14 Sep 2018 (actual)
- Primary completion
- 22 Oct 2020 (actual)
- Study completion
- 6 Nov 2020 (actual)
- First posted
- 23 May 2018 (actual)
- Results
- Posted 7 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Placebo-Controlled, Double-Blind, Parallel-Group
| Arm | Type | Receives |
|---|---|---|
| Active (AMX0035) | Active comparator | Drug: AMX0035AMX0035 twice daily--a combination of Sodium Phenylbutyrate (3g) and Taurursodiol (1g) |
| Placebo | Placebo comparator | Drug: PlaceboTaste-matched Placebo |
Who may qualify
- Ages
- 55 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Ages 55-89, inclusive, male or female
- Diagnosis of "Probable Alzheimer's Disease" or Mild Cognitive Impairment (amnestic or amnestic plus other) with biomarkers that suggest intermediate or high likelihood that the syndrome is due to AD, according to 2011 NIA-AA Workgroup criteria
- MoCA score >/=8
- Able to read and write in English sufficiently to complete all study procedures
- Geriatric Depression Scale <7
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMX0035Also: Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO; also known as Tauroursodeoxycholic Acid [TUDCA])Combination Therapy of PB and TURSO | Drug | Active (AMX0035) |
| PlaceboAlso: ComparatorPlacebo | Drug | Placebo |
Primary outcome
Number of Participants With Treatment-Emergent Adverse Event (TEAEs)
Time frame: From first dose to 24 weeks
Comparison between the AMX0035 Group and Placebo of the number of participants with TEAEs
Effect of Treatment on a Global Composite Statistical Test of Cognition, Function, and Neuroanatomy (GST)
Time frame: 24 weeks
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.
6 secondary outcomes
Effect of Treatment on Cognition
Time frame: 24 weeks
Effect of Treatment on Functioning
Time frame: 24 weeks
Effect of Treatment on Dementia Severity
Time frame: 24 weeks
Effect of Treatment on Cognitive Impairment
Time frame: 24 weeks
Effect of Treatment on Neuropsychiatric Symptoms
Time frame: 24 weeks
Regional Brain Volume
Time frame: 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 39131742Arnold 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.
- Derived from this study: PubMed 37941072Wen 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.
- "Biological effects of sodium phenylbutyrate and taurursodiol in Alzheimer's disease"Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick Yeramian, MD study director
Amylyx Pharmaceuticals Inc.
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AMX0035 in people with Alzheimer Disease, run by Amylyx Pharmaceuticals Inc. at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-Emergent Adverse Event (TEAEs) (time frame: From first dose to 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03533257, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2025.