Study to Assess the Safety and Biological Activity of AMX0035 for the Treatment of Alzheimer's Disease (PEGASUS)
Primary Purpose
Alzheimer Disease
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
AMX0035
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer Disease
Eligibility Criteria
Inclusion Criteria:
- 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 8 - 26 inclusive
- 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
- 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 Tauroursodeoxycholic acid or Phenylbutyrate
- Must have a previous biomarker supportive of AD as the underlying pathology of cognitive decline, which could include amyloid PET, CSF AD biomarkers, FDG-PET, or vMRI scan
- If on cholinesterase inhibitor and/or memantine, doses are stable for 3 months prior to baseline
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
- History of cholecystectomy or biliary disease
- 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:
- 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
- Major active or chronic psychiatric illness (e.g. depression, bipolar disorder, obsessive compulsive disorder, schizophrenia) within the previous year prior to baseline
- Any significant neurodevelopmental disability
- Current suicidal ideation or history of suicide attempt within five 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 two 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 small molecule investigational therapy being used or evaluated for the treatment of AD is prohibited beginning three months (84 days) prior to the Baseline Visit and throughout the study.
- Use of any immunotherapy investigational therapy is prohibited beginning one year (365 days) prior to the Baseline Visit and throughout the study.
- Use of other investigational agents one month (28 days) prior to the Baseline Visit and for the duration of the trial.
Sites / Locations
- CNS Healthcare - Jacksonville
- CNS Healthcare - Orlando
- International Medical Investigational Centers (IMIC)
- Rush University Medical Center
- University of Kansas Clinical Research Center
- Massachusetts General Hospital
- Rowan University
- Mount Sinai Alzheimer's Disease Research Center
- Columbia University
- Penn Memory Center
- Center for Biomedical Research
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Active (AMX0035)
Placebo
Arm Description
AMX0035--a combination of TUDCA and Phenylbutyrate
Taste-matched Placebo
Outcomes
Primary Outcome Measures
Quantity of Adverse Events Observed in the Study
Rate of Adverse Events between Placebo and Active Groups
Secondary Outcome Measures
MRI Volumetric Imaging
Impact of AMX0035 on levels of whole brain atrophy, as assessed by volumetric Magnetic Resonance Imaging (vMRI)
Cognition
Impact of AMX0035 on clinical symptoms as measured by ADAS-Cog
Psychiatric Symptoms
Impact of AMX0035 on measures of neuropsychiatric symptoms as assessed by the Neuropsychiatric Inventory (NPI)
MRI Hippocampal Imaging
Impact of AMX0035 on levels of hippocampal atrophy, as assessed by volumetric Magnetic Resonance Imaging (vMRI)
Functional MRI Imaging
Impact of AMX0035 on rsfMRI
Full Information
NCT ID
NCT03533257
First Posted
April 30, 2018
Last Updated
November 10, 2021
Sponsor
Amylyx Pharmaceuticals Inc.
Collaborators
Alzheimer's Drug Discovery Foundation, Alzheimer's Association
1. Study Identification
Unique Protocol Identification Number
NCT03533257
Brief Title
Study to Assess the Safety and Biological Activity of AMX0035 for the Treatment of Alzheimer's Disease
Acronym
PEGASUS
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
August 27, 2018 (Actual)
Primary Completion Date
April 15, 2021 (Actual)
Study Completion Date
August 15, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amylyx Pharmaceuticals Inc.
Collaborators
Alzheimer's Drug Discovery Foundation, Alzheimer's Association
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The proposed study will be a 24-week, randomized, double-blind, multi-site, placebo-controlled study in volunteers with late 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 volunteers with late 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Placebo-Controlled, Double-Blind, Parallel-Group
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
95 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Active (AMX0035)
Arm Type
Active Comparator
Arm Description
AMX0035--a combination of TUDCA and Phenylbutyrate
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Taste-matched Placebo
Intervention Type
Drug
Intervention Name(s)
AMX0035
Other Intervention Name(s)
Tauroursodeoxycholic Acid and Sodium Phenylbutyrate
Intervention Description
Combination Therapy of TUDCA and Sodium Phenylbutyrate
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Comparator
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Quantity of Adverse Events Observed in the Study
Description
Rate of Adverse Events between Placebo and Active Groups
Time Frame
6 Months
Secondary Outcome Measure Information:
Title
MRI Volumetric Imaging
Description
Impact of AMX0035 on levels of whole brain atrophy, as assessed by volumetric Magnetic Resonance Imaging (vMRI)
Time Frame
6 Months
Title
Cognition
Description
Impact of AMX0035 on clinical symptoms as measured by ADAS-Cog
Time Frame
6 Months
Title
Psychiatric Symptoms
Description
Impact of AMX0035 on measures of neuropsychiatric symptoms as assessed by the Neuropsychiatric Inventory (NPI)
Time Frame
6 Months
Title
MRI Hippocampal Imaging
Description
Impact of AMX0035 on levels of hippocampal atrophy, as assessed by volumetric Magnetic Resonance Imaging (vMRI)
Time Frame
6 Months
Title
Functional MRI Imaging
Description
Impact of AMX0035 on rsfMRI
Time Frame
6 Months
Other Pre-specified Outcome Measures:
Title
CSF Biomarkers
Description
Impact of AMX0035 on CSF biomarkers
Time Frame
6 Months
Title
Plasma Biomarkers
Description
Impact of AMX0035 on plasma biomarkers
Time Frame
6 Months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
89 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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 8 - 26 inclusive
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
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 Tauroursodeoxycholic acid or Phenylbutyrate
Must have a previous biomarker supportive of AD as the underlying pathology of cognitive decline, which could include amyloid PET, CSF AD biomarkers, FDG-PET, or vMRI scan
If on cholinesterase inhibitor and/or memantine, doses are stable for 3 months prior to baseline
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
History of cholecystectomy or biliary disease
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:
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
Major active or chronic psychiatric illness (e.g. depression, bipolar disorder, obsessive compulsive disorder, schizophrenia) within the previous year prior to baseline
Any significant neurodevelopmental disability
Current suicidal ideation or history of suicide attempt within five 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 two 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 small molecule investigational therapy being used or evaluated for the treatment of AD is prohibited beginning three months (84 days) prior to the Baseline Visit and throughout the study.
Use of any immunotherapy investigational therapy is prohibited beginning one year (365 days) prior to the Baseline Visit and throughout the study.
Use of other investigational agents one month (28 days) prior to the Baseline Visit and for the duration of the trial.
Facility Information:
Facility Name
CNS Healthcare - Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32256
Country
United States
Facility Name
CNS Healthcare - Orlando
City
Orlando
State/Province
Florida
ZIP/Postal Code
32801
Country
United States
Facility Name
International Medical Investigational Centers (IMIC)
City
Palmetto Bay
State/Province
Florida
ZIP/Postal Code
33157
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Kansas Clinical Research Center
City
Fairway
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Rowan University
City
Stratford
State/Province
New Jersey
ZIP/Postal Code
08084
Country
United States
Facility Name
Mount Sinai Alzheimer's Disease Research Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Penn Memory Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Center for Biomedical Research
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37909
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Study to Assess the Safety and Biological Activity of AMX0035 for the Treatment of Alzheimer's Disease
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