EARLY

TerminatedPhase 2 / PHASE3Results posted

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

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

Lead sponsor

Janssen Research & Development, LLC

Asset

Atabecestat

Listed sites

128

Recruiting sites

Enrollment

557

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Amyloid biomarker required (PET/CSF)•MRI contraindications excluded

Primary endpoint

•Mini-Mental State Examination (MMSE)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Eudract number2015-000948-42

Secondary ID54861911ALZ2003Janssen Research & Development, LLC

Org study IDCR107373

NCT IDNCT02569398

Timeline

Milestones

Study first posted2015-10-06estimated

Study start2015-10-29actual

Primary completion2018-12-20actual

Study completion2018-12-20actual

Results first posted2020-02-10actual

Last update posted2025-04-29actual

Assets

Drug assets

Atabecestat

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age60 Years

Maximum age85 Years

SexAll

Healthy volunteersAccepted

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)

Endpoints (12)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Global cognition

Memory

Function / daily living

Global cognition

8 endpoints

Primary/protocol endpoint

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

Time frame:Baseline and Endpoint (Month 24)

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Primary/registry result

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

Time frame:Baseline and Endpoint (Month 24)

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (mean), z-score	Standard deviation
Placebon=74 Participants	0.096	1.7261
JNJ-54861911 (5 mg)n=73 Participants	-0.417	1.8372
JNJ-54861911 (25 mg)n=64 Participants	-1.096	1.7796

Secondary/protocol endpoint

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

Time frame:Baseline and Endpoint (Month 24)

change from baseline, improvement

Secondary/protocol endpoint

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

Time frame:Baseline and Endpoint (Month 24)

change from baseline, improvement

Secondary/protocol endpoint

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

Time frame:Baseline and Endpoint (Month 24)

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/registry result

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

Time frame:Baseline and Endpoint (Month 24)

change from baseline, improvement

Posted result

Group	Value (mean), Score on a scale	Standard deviation
PlaceboTotal CFI Participant scoren=28 Participants	-0.04	1.866
Total CFI Informant scoren=27 Participants	-0.22	1.660
JNJ-54861911 (5 mg)Total CFI Participant scoren=27 Participants	0.09	1.135
Total CFI Informant scoren=27 Participants	0.30	1.469
JNJ-54861911 (25 mg)Total CFI Participant scoren=26 Participants	0.75	2.628
Total CFI Informant scoren=26 Participants	0.88	2.475

Secondary/registry result

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

Time frame:Baseline and Endpoint (Month 24)

change from baseline, improvement

Posted result

Group	Value (mean), Score on a scale	Standard deviation
Placebon=124 Participants	2.0	8.90
JNJ-54861911 (5 mg)n=121 Participants	-0.9	7.79
JNJ-54861911 (25 mg)n=114 Participants	-1.7	9.75

Secondary/registry result

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

Time frame:Baseline and Endpoint (Month 24)

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Memory

2 endpoints

Secondary/protocol endpoint

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

Time frame:Baseline and Endpoint (Month 24)

change from baseline, improvement

Secondary/registry result

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

Time frame:Baseline and Endpoint (Month 24)

change from baseline, improvement

Function / daily living

2 endpoints

Secondary/protocol endpoint

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

Time frame:Baseline and Endpoint (Month 24)

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/registry result

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

Time frame:Baseline and Endpoint (Month 24)

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (mean), Score on a Scale	Standard deviation
PlaceboTotal ADL Participant scoren=124 Participants	-0.04	2.975
Total ADL Informant scoren=122 Participants	0.26	4.223
JNJ-54861911 (5 mg)Total ADL Participant scoren=117 Participants	0.35	2.832
Total ADL Informant scoren=115 Participants	-0.12	3.941
JNJ-54861911 (25 mg)Total ADL Participant scoren=110 Participants	0.15	2.834
Total ADL Informant scoren=109 Participants	0.24	4.085

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

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.
PMID33464300via DERIVED

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.