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

Alzheimer Disease Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03533257
• Other study ID #: AMX-8000
• Status: Completed
• Phase: Phase 2
• Start date: August 27, 2018
• Est. completion date: August 15, 2021

Study information

• Verified date: November 2021
• Source: Amylyx Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: August 15, 2021
• Est. primary completion date: April 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 89 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• AMX0035
Combination Therapy of TUDCA and Sodium Phenylbutyrate
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Kansas Clinical Research Center	Fairway	Kansas
United States	CNS Healthcare - Jacksonville	Jacksonville	Florida
United States	Center for Biomedical Research	Knoxville	Tennessee
United States	Columbia University	New York	New York
United States	Mount Sinai Alzheimer's Disease Research Center	New York	New York
United States	CNS Healthcare - Orlando	Orlando	Florida
United States	International Medical Investigational Centers (IMIC)	Palmetto Bay	Florida
United States	Penn Memory Center	Philadelphia	Pennsylvania
United States	Rowan University	Stratford	New Jersey

Sponsors (3)

Lead Sponsor	Collaborator
Amylyx Pharmaceuticals Inc.	Alzheimer's Association, Alzheimer's Drug Discovery Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	CSF Biomarkers	Impact of AMX0035 on CSF biomarkers	6 Months
Other	Plasma Biomarkers	Impact of AMX0035 on plasma biomarkers	6 Months
Primary	Quantity of Adverse Events Observed in the Study	Rate of Adverse Events between Placebo and Active Groups	6 Months
Secondary	MRI Volumetric Imaging	Impact of AMX0035 on levels of whole brain atrophy, as assessed by volumetric Magnetic Resonance Imaging (vMRI)	6 Months
Secondary	Cognition	Impact of AMX0035 on clinical symptoms as measured by ADAS-Cog	6 Months
Secondary	Psychiatric Symptoms	Impact of AMX0035 on measures of neuropsychiatric symptoms as assessed by the Neuropsychiatric Inventory (NPI)	6 Months
Secondary	MRI Hippocampal Imaging	Impact of AMX0035 on levels of hippocampal atrophy, as assessed by volumetric Magnetic Resonance Imaging (vMRI)	6 Months
Secondary	Functional MRI Imaging	Impact of AMX0035 on rsfMRI	6 Months