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

• Status: Completed
• Trial end date: 2021-08-15
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Amylyx Pharmaceuticals Inc.
• Collaborators: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Alzheimer’s Drug Discovery Foundation
• Treatments: 4-phenylbutyric acid; Taurochenodeoxycholic Acid; Tauroursodeoxycholic acid; Ursodoxicoltaurine

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.