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

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ClinicalTrials.gov Identifier: NCT03533257
Recruitment Status : Recruiting
First Posted : May 23, 2018
Last Update Posted : November 5, 2018
Sponsor:
Collaborators:
Alzheimer’s Drug Discovery Foundation
Alzheimer's Association
Information provided by (Responsible Party):
Amylyx Pharmaceuticals Inc.

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
Alzheimer Disease Drug: AMX0035 Drug: Placebo 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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Placebo-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 : August 27, 2018
Estimated Primary Completion Date : July 1, 2020
Estimated Study Completion Date : September 1, 2020


Arm Intervention/treatment
Active Comparator: Active (AMX0035)
AMX0035--a combination of TUDCA and Phenylbutyrate
Drug: AMX0035
Combination Therapy of TUDCA and Sodium Phenylbutyrate
Other Name: Tauroursodeoxycholic Acid and Sodium Phenylbutyrate

Placebo Comparator: Placebo
Taste-matched Placebo
Drug: Placebo
Placebo
Other Name: Comparator




Primary Outcome Measures :
  1. Quantity of Adverse Events Observed in the Study [ Time Frame: 6 Months ]
    Rate of Adverse Events between placebo and Active Groups


Secondary Outcome Measures :
  1. MRI Volumetric Imaging [ Time Frame: 6 Months ]
    Impact of AMX0035 on levels of whole brain atrophy, as assessed by volumetric Magnetic Resonance Imaging (vMRI)

  2. Functional MRI Imaging [ Time Frame: 6 Months ]
    Impact of AMX0035 on cerebral perfusion, as assessed by pseudo-continuous arterial spin-label MRI

  3. Cognition [ Time Frame: 6 Months ]
    Impact of AMX0035 on clinical symptoms as measured by ADAS-Cog

  4. Psychiatric Symptoms [ Time Frame: 6 Months ]
    Impact of AMX0035 on measures of neuropsychiatric symptoms as assessed by the Neuropsychiatric Inventory (NPI)

  5. MRI Hippocampal Imaging [ Time Frame: 6 Months ]
    Impact of AMX0035 on levels of hippocampal atrophy, as assessed by volumetric Magnetic Resonance Imaging (vMRI)


Other Outcome Measures:
  1. CSF Biomarkers [ Time Frame: 6 Months ]
    Impact of AMX0035 on CSF biomarkers

  2. Plasma Biomarkers [ Time Frame: 6 Months ]
    Impact of AMX0035 on plasma-based biomarkers



Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

    1. History of a cardiac pacemaker or pacemaker wires
    2. Metallic particles in the body
    3. Vascular clips in the head
    4. Prosthetic heart valves
    5. Severe claustrophobia impeding ability to participate in an imaging study
  7. Major active or chronic psychiatric illness (e.g. depression, bipolar disorder, obsessive compulsive disorder, schizophrenia) within the previous year prior to baseline
  8. Any significant neurodevelopmental disability
  9. 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
  10. History of alcohol or other substance abuse or dependence within the past two years
  11. Any significant systemic illness or medical condition that could affect safety or compliance with study at the discretion of the Site Investigator
  12. Laboratory abnormalities in B12, TSH, or other common laboratory parameters that might contribute to cognitive dysfunction
  13. Current use of medications with psychoactive properties that may deleteriously affect cognition (e.g., anticholinergics, centrally-acting antihistamines, antipsychotics, sedative hypnotics, anxiolytics)
  14. 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.
  15. Use of any immunotherapy investigational therapy is prohibited beginning one year (365 days) prior to the Baseline Visit and throughout the study.
  16. Use of other investigational agents one month (28 days) prior to the Baseline Visit and for the duration of the trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03533257


Contacts
Contact: Sara Thrower 617-643-5374 Sara.Thrower@mgh.harvard.edu

Locations
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Judy Phillips    312-942-0050    Judy_Phillips@rush.edu   
United States, Kansas
University of Kansas Clinical Research Center Recruiting
Fairway, Kansas, United States, 66205
Contact: KUMC Recruitment Division    913-588-0555    KUAMP@kumc.edu   
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Alison J McManus, DNP    617-643-4848    ajmcmanus@mgh.harvard.edu   
Contact: John Ernandez    617-643-4047    jernandez@partners.org   
United States, New Jersey
Rowan University Not yet recruiting
Stratford, New Jersey, United States, 08084
Contact: Lauren Fedor    856-566-6003    fedor@rowan.edu   
United States, New York
Mount Sinai Alzheimer's Disease Research Center Not yet recruiting
New York, New York, United States, 10029
Contact: Caroline Meuser    212-659-8885    caroline.meuser@mssm.edu   
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Ruth Tejeda    212-305-7661    rbt41@cumc.columbia.edu   
United States, Pennsylvania
Penn Memory Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Laura Schankel    215-349-8727    laura.schankel@pennmedicine.upenn.edu   
Sponsors and Collaborators
Amylyx Pharmaceuticals Inc.
Alzheimer’s Drug Discovery Foundation
Alzheimer's Association

Responsible Party: Amylyx Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT03533257     History of Changes
Other Study ID Numbers: AMX-8000
First Posted: May 23, 2018    Key Record Dates
Last Update Posted: November 5, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
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
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
4-phenylbutyric acid
Tauroursodeoxycholic acid
Taurochenodeoxycholic Acid
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Cholagogues and Choleretics
Gastrointestinal Agents