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

NCT ID: NCT03533257

Last Updated: 2025-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 95 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-14
• Study Completion Date: 2020-11-06

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).

Detailed Description

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). 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. Participants receive orally administered study drug twice daily for a treatment duration of approximately 24 weeks and attend clinic visits at Screening, Baseline, Week 6, Week 12, Week 18, and Week 24.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active (AMX0035)

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

Group Type: ACTIVE_COMPARATOR

AMX0035

Intervention Type: DRUG

Combination Therapy of PB and TURSO

Placebo

Taste-matched Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

AMX0035

Combination Therapy of PB and TURSO

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

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

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 score >/=8

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 TURSO or Phenylbutyrate

10. 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.

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. Recent (less than 1 year) cholecystectomy or the presence of post-cholecystectomy syndrome or biliary obstruction

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, or

MRI findings that show one or more of the following:

1. More than 4 incidental microhemorrhages

2. Incidental lacunar infarct with attributable signs or symptoms and with history of stroke

3. Incidental meningiomas with attributable signs or symptoms

4. Newly recognized meningioma

7. Major active or chronic psychiatric illness (e.g. depression, bipolar disorder, obsessive compulsive disorder, schizophrenia) that is not stable or well controlled within the previous year prior to baseline

8. Any significant neurodevelopmental disability

9. Current suicidal ideation or history of suicide attempt within 5 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 2 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 investigational therapy being used or evaluated for the treatment of AD is prohibited beginning 3 months (90 days) prior to the Baseline Visit and throughout the study.

15. Use of other investigational agents 1 month (28 days) prior to the Baseline Visit and for the duration of the trial.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 89 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alzheimer's Drug Discovery Foundation

OTHER

Sponsor Role: collaborator

Alzheimer's Association

OTHER

Sponsor Role: collaborator

Amylyx Pharmaceuticals Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patrick Yeramian, MD

Role: STUDY_DIRECTOR

Amylyx Pharmaceuticals Inc.

Locations

Clinical Neuroscience Solutions, Inc. - Jacksonville

Jacksonville, Florida, United States

Clinical Neuroscience Solutions, Inc. - Orlando

Orlando, Florida, United States

International Medical Investigational Centers (IMIC)

Palmetto Bay, Florida, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Kansas Clinical Research Center

Fairway, Kansas, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Rowan University School of Osteopathic Medicine

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

Hospital of the University of Pennsylvania, Penn Memory Center

Philadelphia, Pennsylvania, United States

Genesis NeuroScience Clinic

Knoxville, Tennessee, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 39131742 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37941072 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://pubmed.ncbi.nlm.nih.gov/39131742/

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

Other Identifiers

AMX-8000

Identifier Type: -

Identifier Source: org_study_id