An Efficacy and Safety Study of Atabecestat in Participants Who Are Asymptomatic at Risk for Developing Alzheimer's Dementia

NCT ID: NCT02569398

Last Updated: 2025-04-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 557 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-29
• Study Completion Date: 2018-12-20

Brief Summary

The purpose of this study is to evaluate whether treatment with atabecestat slows cognitive decline compared with placebo treatment, as measured by a composite cognitive measure, the Preclinical Alzheimer Cognitive Composite (PACC), in amyloid-positive participants who are asymptomatic at risk for developing Alzheimer's dementia.

Detailed Description

This is a randomized (study drug assigned by chance), double-blind (neither the researchers nor the participants know what treatment the participant is receiving), multi-center (more than one hospital or medical school team work on a medical research study), placebo-controlled, parallel-group study in participants who are asymptomatic and at risk for developing Alzheimer's dementia. The study will consist of a Screening Phase (approximately 90 days), treatment Phase (54 months) and follow-up Phase (7 to 28 days). In treatment Phase eligible Participants will be randomized to receive study drug or placebo once daily for up to 4.5 years. The maximum study duration for a participant will be 58 months. Participants' safety will be monitored throughout the study.

Conditions

Asymptomatic Amyloid-positive

Study Design

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

Study Groups

Group 1

Participants will receive one atabecestat, 5 milligram (mg) tablet orally once daily up to 54 months.

Group Type: EXPERIMENTAL

Atabecestat, 5 mg

Intervention Type: DRUG

One atabecestat, 5 mg tablet orally once daily up to 54 months.

Group 2

Participants will receive one atabecestat, 25 mg tablet orally once daily up to 54 months.

Group Type: EXPERIMENTAL

Atabecestat, 25 mg

Intervention Type: DRUG

One atabecestat, 25 mg tablet orally once daily up to 54 months.

Group 3

Participants will receive one matching placebo tablet orally once daily up to 54 months.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

One matching placebo tablet orally once daily up to 54 months.

Interventions

Atabecestat, 5 mg

One atabecestat, 5 mg tablet orally once daily up to 54 months.

Intervention Type: DRUG

Atabecestat, 25 mg

One atabecestat, 25 mg tablet orally once daily up to 54 months.

Intervention Type: DRUG

Placebo

One matching placebo tablet orally once daily up to 54 months.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participant must have a global Clinical Dementia Rating Scale- (CDR) score of '0' at Screening
• Participants 60 to 64 years of age must also have 1 of the following 3 conditions: a) a positive family history for dementia (minimum of 1 first degree relative), b) a previously known apolipoprotein E, ε4 allele (APOE ɛ4) genotype, c) a previously known biomarker status demonstrating elevated amyloid accumulation in cerebrospinal fluid (CSF) or positron emission tomography (PET)
• Participant must be able to read and write and must have adequate hearing and visual acuity to complete the psychometric tests. The legally acceptable representative must also be able to read and write
• Participants must have evidence of amyloid accumulation by means of either: a) low Cerebrospinal Fluid (CSF) ABeta 1-42 levels at Screening; b) a positive amyloid positron emission tomography (PET) scan at Screening (depending on the site's PET capability) by visual read
• Participant must be otherwise healthy for their age group or medically stable with or without medication on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at Screening or at Baseline

Exclusion Criteria

• Participant is receiving an acetylcholinesterase (AChE) inhibitor and/or memantine at any time during Screening or Day 1 predose
• Participant has evidence of any brain diseases, other than potential very early signs of Alzheimer's Dementia (AD) (example. mild hippocampal atrophy) or typical age-related changes (e.g. mild white matter hyperintensity on magnetic resonance imaging [MRI]) or any other abnormality (e.g. folic acid/Vitamin B12 deficiency) that could explain a possible cognitive deficit (including, but not limited to vascular encephalopathy or large strokes (as imaged by cerebral MRI)
• Participant has any contraindications for MRI (example, prostheses, implants, claustrophobia, pacemaker)
• Participant has met criteria for dementia or has a brain disorder that can cause dementia
• Participant has evidence of familial autosomal dominant AD (mutation identified in the family and/or participant prior to randomization)

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Birmingham, Alabama, United States

Phoenix, Arizona, United States

Sun City, Arizona, United States

Downey, California, United States

La Jolla, California, United States

Newport Beach, California, United States

Orange, California, United States

San Diego, California, United States

New Haven, Connecticut, United States

Washington D.C., District of Columbia, United States

Delray Beach, Florida, United States

Fort Myers, Florida, United States

Jacksonville, Florida, United States

Lake Worth, Florida, United States

Melbourne, Florida, United States

Miami Beach, Florida, United States

Ocoee, Florida, United States

Orlando, Florida, United States

Ormond Beach, Florida, United States

Tampa, Florida, United States

The Villages, Florida, United States

Atlanta, Georgia, United States

Columbus, Georgia, United States

Decatur, Georgia, United States

Arlington Heights, Illinois, United States

Chicago, Illinois, United States

Elk Grove Village, Illinois, United States

Elkhart, Indiana, United States

Indianapolis, Indiana, United States

Iowa City, Iowa, United States

Westwood, Kansas, United States

Lexington, Kentucky, United States

Baton Rouge, Louisiana, United States

Bangor, Maine, United States

Boston, Massachusetts, United States

Plymouth, Massachusetts, United States

Ann Arbor, Michigan, United States

Kalamazoo, Michigan, United States

Hattiesburg, Mississippi, United States

St Louis, Missouri, United States

Las Vegas, Nevada, United States

Amherst, New York, United States

New York, New York, United States

Orangeburg, New York, United States

Rochester, New York, United States

Staten Island, New York, United States

Syracuse, New York, United States

Charlotte, North Carolina, United States

Raleigh, North Carolina, United States

Winston-Salem, North Carolina, United States

Cleveland, Ohio, United States

Portland, Oregon, United States

Willow Grove, Pennsylvania, United States

Providence, Rhode Island, United States

Charleston, South Carolina, United States

Cordova, Tennessee, United States

Nashville, Tennessee, United States

Houston, Texas, United States

San Antonio, Texas, United States

Salt Lake City, Utah, United States

Charlottesville, Virginia, United States

Seattle, Washington, United States

Spokane, Washington, United States

Madison, Wisconsin, United States

Adelaide, , Australia

Brisbane, , Australia

Darlinghurst, , Australia

East Gosford, , Australia

Heidelberg, , Australia

Herston, , Australia

Subiaco, , Australia

Tarren Point, , Australia

Waratah, , Australia

Antwerp, , Belgium

Baudour, , Belgium

Brussels, , Belgium

Edegem, , Belgium

Liège, , Belgium

Mons, , Belgium

Toronto, Ontario, Canada

Gatineau, Quebec, Canada

Aalborg, , Denmark

Ballerup Municipality, , Denmark

København Ø, , Denmark

Rødovre Municipality, , Denmark

Kuopio, , Finland

Turku, , Finland

Berlin, , Germany

Essen, , Germany

Halle, , Germany

Homburg, , Germany

Kiel, , Germany

Mannheim, , Germany

Mittweida, , Germany

Stuttgart, , Germany

Ulm, , Germany

Chiba, , Japan

Fukuoka, , Japan

Hachioji-shi, , Japan

Iizuka-shi, , Japan

Osaka, , Japan

Shibuya-ku, , Japan

Shinjuku-ku, , Japan

Shirakawa, , Japan

Tokyo, , Japan

Chihuahua City, , Mexico

Monterrey, , Mexico

San Luis Potosí City, , Mexico

Tlalnepantla, , Mexico

's-Hertogenbosch, , Netherlands

Amsterdam, , Netherlands

Breda, , Netherlands

Utrecht, , Netherlands

Barcelona, , Spain

Donostia / San Sebastian, , Spain

Getxo, , Spain

Madrid, , Spain

Manresa, , Spain

Terrassa, , Spain

Valencia, , Spain

Mölndal, , Sweden

Birmingham, , United Kingdom

Glasgow, , United Kingdom

Guildford, , United Kingdom

London, , United Kingdom

Newcastle upon Tyne, , United Kingdom

Plymouth, , United Kingdom

Swindon, , United Kingdom

Countries

United States; Australia; Belgium; Canada; Denmark; Finland; Germany; Japan; Mexico; Netherlands; Spain; Sweden; United Kingdom

References

Sperling R, Henley D, Aisen PS, Raman R, Donohue MC, Ernstrom K, Rafii MS, Streffer J, Shi Y, Karcher K, Raghavan N, Tymofyeyev Y, Bogert J, Brashear HR, Novak G, Thipphawong J, Saad ZS, Kolb H, Rofael H, Sanga P, Romano G. Findings of Efficacy, Safety, and Biomarker Outcomes of Atabecestat in Preclinical Alzheimer Disease: A Truncated Randomized Phase 2b/3 Clinical Trial. JAMA Neurol. 2021 Mar 1;78(3):293-301. doi: 10.1001/jamaneurol.2020.4857.

Reference Type: DERIVED

PMID: 33464300 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-000948-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

54861911ALZ2003

Identifier Type: OTHER

Identifier Source: secondary_id

CR107373

Identifier Type: -

Identifier Source: org_study_id