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Asymptomatic Amyloid-positivePhase 2/3EARLYNCT02569398

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

A Phase 2/3 study testing Atabecestat, 5 mg and Atabecestat, 25 mg in people with Asymptomatic Amyloid-positive, run by Janssen Research & Development, LLC at 128 sites in 13 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 60 to 85 yearsHealthy volunteers can take part
Conditions the study is for
Asymptomatic Amyloid-positive
What is being tested?
Atabecestat, 5 mg and Atabecestat, 25 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
557 participants
Where
128 sitesin 13 countries
Study dates
29 Oct 2015to 20 Dec 2018
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 to 85 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)

Trial locations and contacts

128 sites in 13 countries.

128 sites in 13 countries

United States64 sites

  • Study site

    Amherst, New York

  • Study site

    Ann Arbor, Michigan

  • Study site

    Arlington Heights, Illinois

  • Study site

    Atlanta, Georgia

  • Study site

    Bangor, Maine

  • Study site

    Baton Rouge, Louisiana

  • Study site

    Birmingham, Alabama

  • Study site

    Boston, Massachusetts

  • Study site

    Charleston, South Carolina

  • Study site

    Charlotte, North Carolina

  • Study site

    Charlottesville, Virginia

  • Study site

    Chicago, Illinois

  • Study site

    Cleveland, Ohio

  • Study site

    Columbus, Georgia

  • Study site

    Cordova, Tennessee

  • Study site

    Decatur, Georgia

  • Study site

    Delray Beach, Florida

  • Study site

    Downey, California

  • Study site

    Elk Grove Village, Illinois

  • Study site

    Elkhart, Indiana

  • Study site

    Fort Myers, Florida

  • Study site

    Hattiesburg, Mississippi

  • Study site

    Houston, Texas

  • Study site

    Indianapolis, Indiana

  • Study site

    Iowa City, Iowa

  • Study site

    Jacksonville, Florida

  • Study site

    Kalamazoo, Michigan

  • Study site

    La Jolla, California

  • Study site

    Lake Worth, Florida

  • Study site

    Las Vegas, Nevada

  • Study site

    Lexington, Kentucky

  • Study site

    Madison, Wisconsin

  • Study site

    Melbourne, Florida

  • Study site

    Miami Beach, Florida

  • Study site

    Nashville, Tennessee

  • Study site

    New Haven, Connecticut

  • Study site

    New York, New York

  • Study site

    Newport Beach, California

  • Study site

    Ocoee, Florida

  • Study site

    Orange, California

  • Study site

    Orangeburg, New York

  • Study site

    Orlando, Florida

  • Study site

    Ormond Beach, Florida

  • Study site

    Phoenix, Arizona

  • Study site

    Plymouth, Massachusetts

  • Study site

    Portland, Oregon

  • Study site

    Providence, Rhode Island

  • Study site

    Raleigh, North Carolina

  • Study site

    Rochester, New York

  • Study site

    Salt Lake City, Utah

  • Study site

    San Antonio, Texas

  • Study site

    San Diego, California

  • Study site

    Seattle, Washington

  • Study site

    Spokane, Washington

  • Study site

    St Louis, Missouri

  • Study site

    Staten Island, New York

  • Study site

    Sun City, Arizona

  • Study site

    Syracuse, New York

  • Study site

    Tampa, Florida

  • Study site

    The Villages, Florida

  • Study site

    Washington D.C., District of Columbia

  • Study site

    Westwood, Kansas

  • Study site

    Willow Grove, Pennsylvania

  • Study site

    Winston-Salem, North Carolina

Other trials in United States

Australia9 sites

  • Study site

    Adelaide

  • Study site

    Brisbane

  • Study site

    Darlinghurst

  • Study site

    East Gosford

  • Study site

    Heidelberg

  • Study site

    Herston

  • Study site

    Subiaco

  • Study site

    Tarren Point

  • Study site

    Waratah

Other trials in Australia

Germany9 sites

  • Study site

    Berlin

  • Study site

    Essen

  • Study site

    Halle

  • Study site

    Homburg

  • Study site

    Kiel

  • Study site

    Mannheim

  • Study site

    Mittweida

  • Study site

    Stuttgart

  • Study site

    Ulm

Other trials in Germany

Japan9 sites

  • Study site

    Chiba

  • Study site

    Fukuoka

  • Study site

    Hachioji-shi

  • Study site

    Iizuka-shi

  • Study site

    Osaka

  • Study site

    Shibuya-ku

  • Study site

    Shinjuku-ku

  • Study site

    Shirakawa

  • Study site

    Tokyo

Other trials in Japan

Spain7 sites

  • Study site

    Barcelona

  • Study site

    Donostia / San Sebastian

  • Study site

    Getxo

  • Study site

    Madrid

  • Study site

    Manresa

  • Study site

    Terrassa

  • Study site

    Valencia

Other trials in Spain

United Kingdom7 sites

  • Study site

    Birmingham

  • Study site

    Glasgow

  • Study site

    Guildford

  • Study site

    London

  • Study site

    Newcastle upon Tyne

  • Study site

    Plymouth

  • Study site

    Swindon

Other trials in United Kingdom

Belgium6 sites

  • Study site

    Antwerp

  • Study site

    Baudour

  • Study site

    Brussels

  • Study site

    Edegem

  • Study site

    Liège

  • Study site

    Mons

Other trials in Belgium

Denmark4 sites

  • Study site

    Aalborg

  • Study site

    Ballerup Municipality

  • Study site

    København Ø

  • Study site

    Rødovre Municipality

Other trials in Denmark

Mexico4 sites

  • Study site

    Chihuahua City

  • Study site

    Monterrey

  • Study site

    San Luis Potosí City

  • Study site

    Tlalnepantla

Other trials in Mexico

Netherlands4 sites

  • Study site

    's-Hertogenbosch

  • Study site

    Amsterdam

  • Study site

    Breda

  • Study site

    Utrecht

Other trials in Netherlands

Canada2 sites

  • Study site

    Gatineau, Quebec

  • Study site

    Toronto, Ontario

Other trials in Canada

Finland2 sites

  • Study site

    Kuopio

  • Study site

    Turku

Other trials in Finland

Sweden1 site

  • Study site

    Mölndal

Other trials in Sweden

About this study

Official title: A Phase 2b/3 Randomized, Double-blind, Placebo-Controlled, Parallel Group, Multicenter Study Investigating the Efficacy and Safety of JNJ-54861911 in Subjects Who Are Asymptomatic At Risk for Developing Alzheimer's Dementia

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.

Read the 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.

Being tested
Atabecestat, 5 mg, Atabecestat, 25 mg, Placebo
Keywords
Alzheimer disease, Atabecestat, Dementia
Medical subject headings
Alzheimer Disease, Dementia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Atabecestat, 5 mgDrug

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

  • Atabecestat, 25 mgDrug

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

  • PlaceboDrug

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

Study groups in NCT02569398
Study groupRoleWhat they receive
Group 1ExperimentalParticipants will receive one atabecestat, 5 milligram (mg) tablet orally once daily up to 54 months.
Receives: Drug: Atabecestat, 5 mg
Group 2ExperimentalParticipants will receive one atabecestat, 25 mg tablet orally once daily up to 54 months.
Receives: Drug: Atabecestat, 25 mg
Group 3ExperimentalParticipants will receive one matching placebo tablet orally once daily up to 54 months.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in Preclinical Alzheimer Cognitive Composite (PACC) Score at Endpoint (Month 24)

    PACC has 4 components: Free and Cued Selective Reminding Test (0 (worst)-48 (best recall); Delayed Paragraph Recall test (Range 0 (worst)-25 (best recall); Wechsler Adult Intelligence scale: (ranges 0 [none]-135 [best performance]) and Mini Mental State Examination (Range 0 [worst] - 30 [best performance]). Component scores are transformed using an established normalization method into z-scores. Each of 4 component change scores is divided by baseline sample standard deviation (SD) of that component. These z scores are summed to form the composite score. Thus, a change of 1 baseline standard deviation on each component would correspond to a 4-point change on the composite. A z-score of 0 is equal to the mean and implies how many SD higher or lower score as compared with baseline score, with increase signifying improvement.

    Measured: Baseline and Endpoint (Month 24)

Secondary outcomes (5)

  1. Change From Baseline in Cognitive Function Index (CFI) Score at Endpoint (Month 24)

    The CFI is a modified version of the Mail-in Cognitive Function Screening Instrument, a participant- and informant-reported outcome measure developed by the Alzheimer's Disease Cooperative Study (ADCS). This assessment includes 15 questions (14 of which contribute to the total score, and 1 additional unscored item) that assess the participant's perceived ability to perform high-level functional tasks in daily-life and sense of overall cognitive functional ability. Study participants and their informants independently rate the participant's abilities. A participant-reported and an informant-reported total score is calculated which ranges from 0 to 14 (yes=1; no=0; maybe=0.5 for each question) with higher scores indicating greater impairment.

    Measured: Baseline and Endpoint (Month 24)

  2. Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Prevention Instrument (ADCS-ADLPI) Total Score at Endpoint (Month 24)

    The Alzheimer's Disease Cooperative Study - Activities of Daily Living -Prevention Instrument (ADCS-ADLPI) is a functional measure composed of 18 items that includes 15 activities of daily living rated on a 4-point scale and 3 high level function items. Study participants and their informants independently rate the participant's level of ability (with no difficulty = 3, with some difficulty = 2, with a lot of difficulty = 1, did not do/don't know = 0). Informants are additionally asked to evaluate whether activities were completed less often, required more time to complete, and if any errors were made performing the task. High-level function items are rated as "yes" or "no". The scores range from 0 to 45 with higher scores indicating less impairment. The total score is the sum of the scores of the 15 activities of daily living questions (range: 0-45) with higher scores indicating less impairment.

    Measured: Baseline and Endpoint (Month 24)

  3. Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Score at Endpoint (Month 24)

    RBANS is 20 to 25 minute battery developed for cognitive assessment, detection, and characterization of dementia. RBANS includes 12 subtests that measure following 5 indices: (1)Attention Index, composed of Digit Span and Coding; (2)Language Index, consisting of Picture Naming and Semantic Fluency subtests; (3)Visuospatial/Construction Index, made up of Figure Copy and Line Orientation subtests; (4)Immediate Memory Index, composed of List Learning and Story Memory subtests, and (5)Delayed Memory Index, consisting of List Recall, List Recognition, Story Recall, and Figure Recall subtests. Completion of RBANS yields 5 index scores based on participant performance on various subtests, as well as a composite Total Index score for battery. Total index scores range from 40 to 160, and are normalized to a mean of 100 and standard deviation (SD) of 15. Higher scores indicate less impairment.

    Measured: Baseline and Endpoint (Month 24)

  4. Change From Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score at Endpoint (Month 24)

    The CDR-SB is an interviewer administered scale and impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2 and severe = 3. The 6 individual category ratings, or "box scores", were added together to give the CDR-Sum of Boxes which ranges from 0-18. Higher score indicates severe impairment.

    Measured: Baseline and Endpoint (Month 24)

  5. Change From Baseline in Neuropsychological Assessment Battery Daily Living Tests (NABDLTs) Score at Endpoint (Month 24)

    The Neuropsychological Assessment Battery Daily Living Tests (NABDLTs) Score represent a series of performance based measures covering 5 domains (Attention, Memory, Language, Spatial, and Executive function). These are valid, clinically meaningful measures that objectively assess functional deficits. Participant performance scores on NAB subtests are summed, and then normalized to yield an index score. Index scores can range from less than or equal to (< =) 55 to greater than or equal to (> =) 145, and are normalized to a mean of 100 and standard deviation of 15. Higher scores indicate less impairment.

    Measured: Baseline and Endpoint (Month 24)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Oct 2015 (estimated)
  2. Study start29 Oct 2015
  3. Primary completion20 Dec 2018
  4. Study completion20 Dec 2018

Why it stopped: Change in benefit-risk profile for individuals with early sporadic Alzheimer Disease because of elevations in liver enzymes in subjects receiving atabecestat

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
557 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02569398
Sponsor's protocol ID
CR107373
Other IDs
2015-000948-42, 54861911ALZ2003, 2015
Acronym
EARLY
Status last verified
Apr 2025
First submitted
5 Oct 2015
Last updated
29 Apr 2025
Data monitoring committee
Yes
FDA-regulated device
No

Publications

  • Ritchie M, Raman R, Ernstrom K, Wang S, Donohue MC, Aisen P, Henley D, Romano G, Novak GP, Brashear HR, Sperling RA, Grill JD. Views and Perceptions of Amyloid Imaging in a Preclinical Alzheimer's Disease Trial. J Prev Alzheimers Dis. 2024;11(6):1563-1571. doi: 10.14283/jpad.2024.157.

    PubMed 39559869

  • 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.

    PubMed 33464300

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Atabecestat, 5 mg and Atabecestat, 25 mg in people with Asymptomatic Amyloid-positive, run by Janssen Research & Development, LLC at 128 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 29 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 128 sites in United States, Australia, Germany, Japan, Spain and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Preclinical Alzheimer Cognitive Composite (PACC) Score at Endpoint (Month 24) (time frame: Baseline and Endpoint (Month 24)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02569398, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2025; AzTrials last refreshed its copy on 8 Nov 2026.

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