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

Phase 2

Completed

• Conditions: Alzheimer Disease
• Interventions: Drug: AMX0035; Drug: Placebo

• Registration Number: NCT03533257
• Lead Sponsor: 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).

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-04-30
• Study First Submitted QC: 2018-05-10
• Study First Posted: 2018-05-23
• Study Start: 2018-08-27
• Primary Completion: 2021-04-15
• Study Completion: 2021-08-15
• Status Verified: 2021-11
• Last Update Submitted: 2021-11-10
• Last Update Posted: 2021-11-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 95

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active (AMX0035)	AMX0035	AMX0035--a combination of TUDCA and Phenylbutyrate
Placebo	Placebo	Taste-matched Placebo

Primary Outcome Measures

Name	Time	Method
Quantity of Adverse Events Observed in the Study	6 Months	Rate of Adverse Events between Placebo and Active Groups

Secondary Outcome Measures

Name	Time	Method
MRI Volumetric Imaging	6 Months	Impact of AMX0035 on levels of whole brain atrophy, as assessed by volumetric Magnetic Resonance Imaging (vMRI)
Cognition	6 Months	Impact of AMX0035 on clinical symptoms as measured by ADAS-Cog
Psychiatric Symptoms	6 Months	Impact of AMX0035 on measures of neuropsychiatric symptoms as assessed by the Neuropsychiatric Inventory (NPI)
MRI Hippocampal Imaging	6 Months	Impact of AMX0035 on levels of hippocampal atrophy, as assessed by volumetric Magnetic Resonance Imaging (vMRI)
Functional MRI Imaging	6 Months	Impact of AMX0035 on rsfMRI

Trial Locations

Locations (11)

University of Kansas Clinical Research Center; 🇺🇸 Fairway, Kansas, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Penn Memory Center; 🇺🇸 Philadelphia, Pennsylvania, United States

International Medical Investigational Centers (IMIC); 🇺🇸 Palmetto Bay, Florida, United States

CNS Healthcare - Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

CNS Healthcare - Orlando; 🇺🇸 Orlando, Florida, United States

Rowan University; 🇺🇸 Stratford, New Jersey, United States

Mount Sinai Alzheimer's Disease Research Center; 🇺🇸 New York, New York, United States

Columbia University; 🇺🇸 New York, New York, United States

Center for Biomedical Research; 🇺🇸 Knoxville, Tennessee, United States