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

Sponsor
Amylyx Pharmaceuticals Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT03533257
Collaborator
Alzheimer's Drug Discovery Foundation (Other), Alzheimer's Association (Other)
95
Enrollment
11
Locations
2
Arms
35.6
Actual Duration (Months)
8.6
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

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).

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
95 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Placebo-Controlled, Double-Blind, Parallel-GroupPlacebo-Controlled, Double-Blind, Parallel-Group
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Aug 27, 2018
Actual Primary Completion Date :
Apr 15, 2021
Actual Study Completion Date :
Aug 15, 2021

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Active (AMX0035)

AMX0035--a combination of TUDCA and Phenylbutyrate

Drug: AMX0035
Combination Therapy of TUDCA and Sodium Phenylbutyrate
Other Names:
  • Tauroursodeoxycholic Acid and Sodium Phenylbutyrate

    		•
    Placebo Comparator: Placebo

    Taste-matched Placebo

    Drug: Placebo
    Placebo
    Other Names:
  • Comparator

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Quantity of Adverse Events Observed in the Study [6 Months]

      Rate of Adverse Events between Placebo and Active Groups

    Secondary Outcome Measures

    1. MRI Volumetric Imaging [6 Months]

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

    2. Cognition [6 Months]

      Impact of AMX0035 on clinical symptoms as measured by ADAS-Cog

    3. Psychiatric Symptoms [6 Months]

      Impact of AMX0035 on measures of neuropsychiatric symptoms as assessed by the Neuropsychiatric Inventory (NPI)

    4. MRI Hippocampal Imaging [6 Months]

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

    5. Functional MRI Imaging [6 Months]

      Impact of AMX0035 on rsfMRI

    Other Outcome Measures

    1. CSF Biomarkers [6 Months]

      Impact of AMX0035 on CSF biomarkers

    2. Plasma Biomarkers [6 Months]

      Impact of AMX0035 on plasma biomarkers

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    55 Years to 89 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Ages 55-89, inclusive, male or female

    2. 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

    3. MoCA 8 - 26 inclusive

    4. Able to read and write in English sufficiently to complete all study procedures

    5. Geriatric Depression Scale <7

    6. Willing and able to complete all assessments and study procedures

    7. Not pregnant, lactating or of child-bearing potential (women must be >2 years post-menopausal or surgically sterile)

    8. Study partner with at least two days per week with contact with patient willing to accompany patient to visits and complete partner study forms

    9. No known hypersensitivity to Tauroursodeoxycholic acid or Phenylbutyrate

    10. 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

    11. If on cholinesterase inhibitor and/or memantine, doses are stable for 3 months prior to baseline

    Exclusion Criteria:

    1. 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

    2. Abnormal liver function defined as AST and/or ALT > 3 times the upper limit of normal

    3. Renal insufficiency as defined by a serum creatinine > 1.5 times the upper limit of normal

    4. History of cholecystectomy or biliary disease

    5. 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

    6. Any contraindication to undergo MRI studies such as:

    7. History of a cardiac pacemaker or pacemaker wires

    8. Metallic particles in the body

    9. Vascular clips in the head

    10. Prosthetic heart valves

    11. Severe claustrophobia impeding ability to participate in an imaging study

    12. Major active or chronic psychiatric illness (e.g. depression, bipolar disorder, obsessive compulsive disorder, schizophrenia) within the previous year prior to baseline

    13. Any significant neurodevelopmental disability

    14. 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

    15. History of alcohol or other substance abuse or dependence within the past two years

    16. Any significant systemic illness or medical condition that could affect safety or compliance with study at the discretion of the Site Investigator

    17. Laboratory abnormalities in B12, TSH, or other common laboratory parameters that might contribute to cognitive dysfunction

    18. Current use of medications with psychoactive properties that may deleteriously affect cognition (e.g., anticholinergics, centrally-acting antihistamines, antipsychotics, sedative hypnotics, anxiolytics)

    19. 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.

    20. Use of any immunotherapy investigational therapy is prohibited beginning one year (365 days) prior to the Baseline Visit and throughout the study.

    21. Use of other investigational agents one month (28 days) prior to the Baseline Visit and for the duration of the trial.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 CNS Healthcare - Jacksonville Jacksonville Florida United States 32256
    2 CNS Healthcare - Orlando Orlando Florida United States 32801
    3 International Medical Investigational Centers (IMIC) Palmetto Bay Florida United States 33157
    4 Rush University Medical Center Chicago Illinois United States 60612
    5 University of Kansas Clinical Research Center Fairway Kansas United States 66205
    6 Massachusetts General Hospital Boston Massachusetts United States 02114
    7 Rowan University Stratford New Jersey United States 08084
    8 Mount Sinai Alzheimer's Disease Research Center New York New York United States 10029
    9 Columbia University New York New York United States 10032
    10 Penn Memory Center Philadelphia Pennsylvania United States 19104
    11 Center for Biomedical Research Knoxville Tennessee United States 37909

    Sponsors and Collaborators

    • Amylyx Pharmaceuticals Inc.
    • Alzheimer's Drug Discovery Foundation
    • Alzheimer's Association

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Amylyx Pharmaceuticals Inc.
    ClinicalTrials.gov Identifier:
    NCT03533257
    Other Study ID Numbers:
    • AMX-8000
    First Posted:
    May 23, 2018
    Last Update Posted:
    Nov 11, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Alzheimer Disease
    Ursodoxicoltaurine
    4-phenylbutyric acid

    Study Results

    No Results Posted as of Nov 11, 2021