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

NCT03533257 | Completed Phase 2 Results FDA Drug

• 1 other identifier: AMX-8000
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 11

Brief Summary

The study is a 24-week, randomized, double-blind, multi-site, placebo-controlled study in participants with mild cognitive impairment (MCI) or early dementia due to Alzheimer's disease (AD).

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-Emergent Adverse Event (TEAEs)

  Comparison between the AMX0035 Group and Placebo of the number of participants with TEAEs

  From first dose to 24 weeks

• Effect of Treatment on a Global Composite Statistical Test of Cognition, Function, and Neuroanatomy (GST)

  Change from Baseline in GST (global statistical test combining three measures relevant to disease trajectory (cognition \[MADCOMS: Mild/Moderate Alzheimer's Disease Composite Score\], function \[FAQ: Functional Activities Questionnaire\], and total hippocampal volume on magnetic resonance imaging)) for AMX0035 relative to placebo. For MADCOMS and FAQ, a higher score indicates a worse outcome. A larger hippocampal volume is better, so it was reversed before being normalized. Each of the three were normalized against respective baseline means and standard deviations. The mean of the three normalized scores is the final GST. A higher GST score indicates a worse outcome. Standard deviations above the mean are worse; standard deviations below the mean are better. The expected value of the GST at baseline is 0 because it is the mean of three z-scores whose expected values at baseline are 0. AD is multifaceted and the GST was designed to be sensitive to changes in multiple dimensions.

  24 weeks

Secondary Outcomes (6)

• Effect of Treatment on Cognition

  24 weeks

• Effect of Treatment on Functioning

  24 weeks

• Effect of Treatment on Dementia Severity

  24 weeks

• Effect of Treatment on Cognitive Impairment

  24 weeks

• Effect of Treatment on Neuropsychiatric Symptoms

  24 weeks

Study Arms (2)

Active (AMX0035)

ACTIVE COMPARATOR

AMX0035 twice daily--a combination of Sodium Phenylbutyrate (3g) and Taurursodiol (1g)

Drug: AMX0035

Placebo

PLACEBO COMPARATOR

Taste-matched Placebo

Drug: Placebo

Interventions

AMX0035 DRUG

Combination Therapy of PB and TURSO

Also known as: Sodium Phenylbutyrate (PB) and Taurursodiol (TURSO; also known as Tauroursodeoxycholic Acid [TUDCA])

Active (AMX0035)

Placebo DRUG

Placebo

Also known as: Comparator

Placebo

Eligibility Criteria

• Age: 55 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 55-89, inclusive, male or female
• 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
• MoCA score \>/=8
• Able to read and write in English sufficiently to complete all study procedures
• Geriatric Depression Scale \<7
• Willing and able to complete all assessments and study procedures
• Not pregnant, lactating or of child-bearing potential (women must be \>2 years post-menopausal or surgically sterile)
• Study partner with at least two days per week with contact with patient willing to accompany patient to visits and complete partner study forms
• No known hypersensitivity to TURSO or Phenylbutyrate
• If on cholinesterase inhibitor and/or memantine, treatment must have started for no less than 3 months (84 days) prior to baseline and the dosing regimen must have remained stable for 6 weeks (42 days) prior to baseline. The Investigator anticipated that the dosing regimen at baseline would remain unchanged throughout participation in the study.

You may not qualify if:

• 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
• Abnormal liver function defined as AST and/or ALT \> 3 times the upper limit of normal
• Renal insufficiency as defined by a serum creatinine \> 1.5 times the upper limit of normal
• Recent (less than 1 year) cholecystectomy or the presence of post-cholecystectomy syndrome or biliary obstruction
• 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
• Any contraindication to undergo MRI studies such as:
• History of a cardiac pacemaker or pacemaker wires
• Metallic particles in the body
• Vascular clips in the head
• Prosthetic heart valves
• Severe claustrophobia impeding ability to participate in an imaging study, or
• MRI findings that show one or more of the following:
• More than 4 incidental microhemorrhages
• Incidental lacunar infarct with attributable signs or symptoms and with history of stroke
• Incidental meningiomas with attributable signs or symptoms

Sponsors & Collaborators

• Amylyx Pharmaceuticals Inc.: lead
• Alzheimer's Drug Discovery Foundation: collaborator
• Alzheimer's Association: collaborator

Study Sites (11)

Clinical Neuroscience Solutions, Inc. - Jacksonville

Jacksonville, Florida, 32256, United States

Location

Clinical Neuroscience Solutions, Inc. - Orlando

Orlando, Florida, 32801, United States

Location

International Medical Investigational Centers (IMIC)

Palmetto Bay, Florida, 33157, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Rowan University School of Osteopathic Medicine

Stratford, New Jersey, 08084, United States

Location

Mount Sinai Alzheimer's Disease Research Center

New York, New York, 10029, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Hospital of the University of Pennsylvania, Penn Memory Center

Philadelphia, Pennsylvania, 19104, United States

Location

Genesis NeuroScience Clinic

Knoxville, Tennessee, 37909, United States

Location

Related Publications (2)

• Arnold SE, Hendrix S, Nicodemus-Johnson J, Knowlton N, Williams VJ, Burns JM, Crane M, McManus AJ, Vaishnavi SN, Arvanitakis Z, Neugroschl J, Bell K, Trombetta BA, Carlyle BC, Kivisakk P, Dodge HH, Tanzi RE, Yeramian PD, Leslie K. Biological effects of sodium phenylbutyrate and taurursodiol in Alzheimer's disease. Alzheimers Dement (N Y). 2024 Aug 9;10(3):e12487. doi: 10.1002/trc2.12487. eCollection 2024 Jul-Sep.

  PMID: 39131742 RESULT

• Wen ZQ, Lin J, Xie WQ, Shan YH, Zhen GH, Li YS. Insights into the underlying pathogenesis and therapeutic potential of endoplasmic reticulum stress in degenerative musculoskeletal diseases. Mil Med Res. 2023 Nov 9;10(1):54. doi: 10.1186/s40779-023-00485-5.

  PMID: 37941072 DERIVED

Related Links

• "Biological effects of sodium phenylbutyrate and taurursodiol in Alzheimer's disease"

MeSH Terms

Conditions

Alzheimer Disease

Interventions

sodium phenylbutyrate and taurursodiol; 4-phenylbutyric acid; ursodoxicoltaurine

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Amylyx Pharmaceuticals, Inc.

medinfo@amylyx.com

(877) 374-1208

Study Officials

• Patrick Yeramian, MD

  Amylyx Pharmaceuticals Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Placebo-Controlled, Double-Blind, Parallel-Group

Study Record Dates

• First Submitted: April 30, 2018
• First Posted: May 23, 2018
• Study Start: September 14, 2018
• Primary Completion: October 22, 2020
• Study Completion: November 6, 2020
• Last Updated: March 7, 2025
• Results First Posted: March 7, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)