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

• ClinicalTrials.gov Identifier: NCT03533257
• Recruitment Status: Recruiting
• First Posted: May 23, 2018
• Last Update Posted: October 4, 2019
• Sponsor: Amylyx Pharmaceuticals Inc.
• Collaborators: Alzheimer’s Drug Discovery Foundation; Alzheimer's Association
• Information provided by (Responsible Party): Amylyx Pharmaceuticals Inc.

Tracking Information

• First Submitted Date: April 30, 2018
• First Posted Date: May 23, 2018
• Last Update Posted Date: October 4, 2019
• Actual Study Start Date: August 27, 2018
• Estimated Primary Completion Date: July 1, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 10, 2018)

Quantity of Adverse Events Observed in the Study [ Time Frame: 6 Months ]

Rate of Adverse Events between placebo and Active Groups

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03533257 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: October 2, 2019)

• MRI Volumetric Imaging [ Time Frame: 6 Months ]
  Impact of AMX0035 on levels of whole brain atrophy, as assessed by volumetric Magnetic Resonance Imaging (vMRI)
• Cognition [ Time Frame: 6 Months ]
  Impact of AMX0035 on clinical symptoms as measured by ADAS-Cog
• Psychiatric Symptoms [ Time Frame: 6 Months ]
  Impact of AMX0035 on measures of neuropsychiatric symptoms as assessed by the Neuropsychiatric Inventory (NPI)
• MRI Hippocampal Imaging [ Time Frame: 6 Months ]
  Impact of AMX0035 on levels of hippocampal atrophy, as assessed by volumetric Magnetic Resonance Imaging (vMRI)
• Functional MRI Imaging [ Time Frame: 6 Months ]
  Impact of AMX0035 on cerebral perfusion, as assessed by pseudo-continuous arterial spin-label MRI

Original Secondary Outcome Measures (submitted: May 10, 2018)

• MRI Volumetric Imaging [ Time Frame: 6 Months ]
  Impact of AMX0035 on levels of whole brain atrophy, as assessed by volumetric Magnetic Resonance Imaging (vMRI)
• Functional MRI Imaging [ Time Frame: 6 Months ]
  Impact of AMX0035 on cerebral perfusion, as assessed by pseudo-continuous arterial spin-label MRI
• Cognition [ Time Frame: 6 Months ]
  Impact of AMX0035 on clinical symptoms as measured by ADAS-Cog
• Psychiatric Symptoms [ Time Frame: 6 Months ]
  Impact of AMX0035 on measures of neuropsychiatric symptoms as assessed by the Neuropsychiatric Inventory (NPI)
• MRI Hippocampal Imaging [ Time Frame: 6 Months ]
  Impact of AMX0035 on levels of hippocampal atrophy, as assessed by volumetric Magnetic Resonance Imaging (vMRI)

Current Other Pre-specified Outcome Measures (submitted: May 10, 2018)

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

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Study to Assess the Safety and Biological Activity of AMX0035 for the Treatment of Alzheimer's Disease
• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

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

• Condition: Alzheimer Disease

Intervention

• Drug: AMX0035
  Combination Therapy of TUDCA and Sodium Phenylbutyrate
  Other Name: Tauroursodeoxycholic Acid and Sodium Phenylbutyrate
• Drug: Placebo
  Placebo
  Other Name: Comparator

Study Arms

• Active Comparator: Active (AMX0035)
  AMX0035--a combination of TUDCA and Phenylbutyrate
  Intervention: Drug: AMX0035
• Placebo Comparator: Placebo
  Taste-matched Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 23, 2019): 100
• Original Estimated Enrollment (submitted: May 10, 2018): 50
• Estimated Study Completion Date: September 1, 2020
• Estimated Primary Completion Date: July 1, 2020 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years to 89 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Beth Benesh; 617-643-5374; BBENESH@mgh.harvard.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03533257
• Other Study ID Numbers: AMX-8000
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Amylyx Pharmaceuticals Inc.
• Study Sponsor: Amylyx Pharmaceuticals Inc.

Collaborators

• Alzheimer’s Drug Discovery Foundation
• Alzheimer's Association

• Investigators: Not Provided
• PRS Account: Amylyx Pharmaceuticals Inc.
• Verification Date: October 2018