TerminatedPhase 2Results posted

An Extension Study to Evaluate the Long-Term Safety and Tolerability of JNJ-54861911 in Participants in the Early Alzheimer's Disease Spectrum

A Randomized, Two-Period, Double-Blind Placebo-Controlled and Open-Label, Multicenter Extension Study to Determine the Long-Term Safety and Tolerability of JNJ-54861911 in Subjects in the Early Alzheimer's Disease Spectrum

Lead sponsor

Janssen Research & Development, LLC

Asset

Atabecestat

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease

Key I/E criterion

•Age 50-85

Primary endpoint

•Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

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 number2014-004274-41

Secondary ID54861911ALZ2004Janssen Research & Development, LLC

Org study IDCR106978

NCT IDNCT02406027

Timeline

Milestones

Study first posted2015-04-01estimated

Study start2015-07-02actual

Primary completion2018-06-28actual

Study completion2018-06-28actual

Results first posted2019-09-09actual

Last update posted2025-04-29actual

Assets

Drug assets

Atabecestat

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Participants in the early Alzheimer's disease (AD) spectrum at time of enrollment under the parent protocol and according to its inclusion and exclusion criteria, must have very recently completed their treatment in a Phase 1b or Phase 2 JNJ-54861911 clinical study (example [e.g.], 54861911ALZ2002) under the parent protocol. Enrollment in this study should be completed (Day 1 of double-blind [DB] treatment phase) as soon as possible, but within 6 weeks, following completion of their treatment period under the parent protocol. If not defined under the parent protocol, completion of the treatment period is defined as having completed all study related procedures of the last visit of the treatment period under the parent protocol. A screening phase of up to 12 weeks may be allowed following written approval of the Sponsor

•Participant must be willing and able to adhere to the prohibitions and restrictions specified in this protocol

•Each Participants (or their legally acceptable representative and caregiver depending on disease state and local requirements) must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study

•Participants must have a reliable informant (relative, partner, or friend). The informant must be willing to participate as a source of information and has at least weekly contact with the participant (contact can be in-person, via telephone or other audio/visual communication). The informant must have sufficient contact such that the Investigator feels he/she can provide meaningful information about the participant's daily function. If possible, an alternate informant meeting these criteria who can replace the primary informant should be identified prior to randomization

Exclusion criteria

•Any condition or situation which, in the opinion of the Investigator, may put the participant at significant risk, may confound the study results, or may interfere significantly with participant's participation in the study

•The use of concomitant medications known to prolong the QT/QTc interval

•Participant has a history of moderate or severe hepatic impairment or severe renal insufficiency unless completely resolved for more than a year. Participant has clinically significant ongoing hepatic, renal, cardiac, vascular, pulmonary, gastrointestinal, endocrine, hematologic, rheumatologic, psychiatric or metabolic conditions (e.g., requiring frequent monitoring or medication adjustments or is otherwise unstable)

Endpoints (10)

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

Amyloid biomarkers

Global cognition

Tau biomarkers

Safety / tolerability / PK

Global cognition

2 endpoints

Secondary/protocol endpoint

Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels

Time frame:Baseline, Double-blind (DB) Day 1 and DB Week 52

percent change from baseline, improvement

Secondary/registry result

Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels

Time frame:Baseline, Double-blind (DB) Day 1 and DB Week 52

percent change from baseline, improvement

Posted result

Group	Value (mean), Percent change	Standard deviation
Double-blind Treatment Phase (Period 1): PlaceboCSF ABeta 1-37: Asymptomatic at Risk: DB Week 52n=4 Participants	-9.9	7.32
CSF ABeta 1-37: Prodromal: DB Day 1n=3 Participants	6.1	10.09
CSF ABeta 1-37: Prodromal: DB Week 52n=8 Participants	-8.8	17.75
CSF ABeta 1-38: Asymptomatic at Risk: DB Week 52n=4 Participants	-9.3	7.02
CSF ABeta 1-38: Prodromal: DB Day 1n=3 Participants	10.2	15.41
CSF ABeta 1-38: Prodromal: DB Week 52n=10 Participants	-9.7	16.52
CSF ABeta 1-40: Asymptomatic at Risk: DB Week 52n=4 Participants	-9.7	6.12
CSF ABeta 1-40: Prodromal: DB Day 1n=3 Participants	8.6	17.19
CSF ABeta 1-40: Prodromal: DB Week 52n=12 Participants	-14.5	20.48
CSF ABeta 1-42: Asymptomatic at Risk: DB Week 52n=4 Participants	-10.1	7.81
CSF ABeta 1-42: Prodromal: DB Day 1n=3 Participants	8.0	7.44
CSF ABeta 1-42: Prodromal: DB Week 52n=12 Participants	-15.0	20.51
Double-blind Treatment Phase (Period 1): Atabecestat 10 mgCSF ABeta 1-37: Asymptomatic at Risk: DB Week 52n=1 Participants	-65.4	NA
CSF ABeta 1-37: Prodromal: DB Week 52n=8 Participants	-62.0	11.02
CSF ABeta 1-38: Asymptomatic at Risk: DB Week 52n=3 Participants	-42.9	17.49
CSF ABeta 1-38: Prodromal: DB Week 52n=9 Participants	-58.6	10.21
CSF ABeta 1-40: Asymptomatic at Risk: DB Week 52n=3 Participants	-46.2	18.22
CSF ABeta 1-40: Prodromal: DB Week 52n=9 Participants	-60.7	13.52
CSF ABeta 1-42: Asymptomatic at Risk: DB Week 52n=3 Participants	-39.6	24.28
CSF ABeta 1-42: Prodromal: DB Week 52n=9 Participants	-52.5	11.60
Double-blind Treatment Phase(Period 1): Atabecestat, 25 mgCSF ABeta 1-37: Asymptomatic at Risk: DB Week 52n=1 Participants	-90.0	NA
CSF ABeta 1-37: Prodromal: DB Week 52n=5 Participants	-65.9	23.16
CSF ABeta 1-38: Asymptomatic at Risk: DB Week 52n=2 Participants	-83.5	4.84
CSF ABeta 1-38: Prodromal: DB Week 52n=10 Participants	-70.4	23.53
CSF ABeta 1-40: Asymptomatic at Risk: DB Week 52n=2 Participants	-84.6	5.43
CSF ABeta 1-40: Prodromal: DB Week 52n=10 Participants	-72.8	22.30
CSF ABeta 1-42: Asymptomatic at Risk: DB Week 52n=2 Participants	-76.7	11.01
CSF ABeta 1-42: Prodromal: DB Week 52n=10 Participants	-57.6	31.42

Amyloid biomarkers

4 endpoints

Secondary/protocol endpoint

Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels

Time frame:Baseline, DB Day 1 and DB Week 52

percent change from baseline, improvement

Secondary/protocol endpoint

Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels

Time frame:Baseline, DB Day 1, DB Week 24, and DB Week 52

percent change from baseline, improvement

Secondary/registry result

Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels

Time frame:Baseline, DB Day 1 and DB Week 52

percent change from baseline, improvement

Posted result

Group	Value (mean), Percent change	Standard deviation
Double-blind Treatment Phase (Period 1): PlaceboCSF sAPP-alpha: Asymptomatic at Risk: DB Week 52n=4 Participants	-4.7	12.78
CSF sAPP-alpha: Prodromal: DB Day 1n=3 Participants	0.9	24.97
CSF sAPP-alpha: Prodromal: DB Week 52n=12 Participants	-11.2	14.01
CSF sAPP-Beta: Asymptomatic at Risk: DB Week 52n=4 Participants	-10.8	8.44
CSF sAPP-Beta: Prodromal: DB Day 1n=3 Participants	0.4	18.93
CSF sAPP-Beta: Prodromal: DB Week 52n=12 Participants	-11.7	14.47
Double-blind Treatment Phase (Period 1): Atabecestat 10 mgCSF sAPP-alpha: Asymptomatic at Risk: DB Week 52n=3 Participants	50.1	13.67
CSF sAPP-alpha: Prodromal: DB Week 52n=9 Participants	60.2	24.03
CSF sAPP-Beta: Asymptomatic at Risk: DB Week 52n=3 Participants	-57.5	8.06
CSF sAPP-Beta: Prodromal: DB Week 52n=9 Participants	-63.5	5.19
Double-blind Treatment Phase(Period 1): Atabecestat, 25 mgCSF sAPP-alpha: Asymptomatic at Risk: DB Week 52n=1 Participants	77.8	NA
CSF sAPP-alpha: Prodromal: DB Week 52n=11 Participants	85.1	39.35
CSF sAPP-Beta: Asymptomatic at Risk: DB Week 52n=1 Participants	-90.8	NA
CSF sAPP-Beta: Prodromal: DB Week 52n=11 Participants	-73.0	21.79

Secondary/registry result

Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels

Time frame:Baseline, DB Day 1, DB Week 24, and DB Week 52

percent change from baseline, improvement

Posted result

Group	Value (mean), Percent change	Standard deviation
Double-blind Treatment Phase (Period 1): PlaceboPlasma ABeta 1-38:Asymptomatic at Risk: DB Week 24n=2 Participants	-9.9	0.83
Plasma ABeta 1-38: Asymptomatic at Risk:DB Week 52n=1 Participants	-5.3	NA
Plasma ABeta 1-38: Prodromal: DB Day 1n=4 Participants	-5.0	10.07
Plasma ABeta 1-38: Prodromal: DB Week 24n=4 Participants	3.0	24.32
Plasma ABeta 1-38: Prodromal: DB Week 52n=3 Participants	20.3	35.48
Plasma ABeta 1-40: Asymptomatic at Risk: DB Day 1n=1 Participants	19.2	NA
Plasma ABeta 1-40:Asymptomatic at Risk: DB Week 24n=5 Participants	-2.3	12.38
Plasma ABeta 1-40:Asymptomatic at Risk: DB Week 52n=5 Participants	0.0	10.85
Plasma ABeta 1-40: Prodromal: DB Day 1n=12 Participants	2.9	15.48
Plasma ABeta 1-40: Prodromal: DB Week 24n=21 Participants	8.6	18.57
Plasma ABeta 1-40: Prodromal: DB Week 52n=18 Participants	10.5	17.09
Plasma ABeta 1-42: Asymptomatic at Risk: DB Day 1n=1 Participants	-5.9	NA
Plasma ABeta 1-42:Asymptomatic at Risk:DB Week 24n=3 Participants	-7.3	9.33
Plasma ABeta 1-42:Asymptomatic at Risk: DB Week 52n=3 Participants	-6.0	2.69
Plasma ABeta 1-42: Prodromal: DB Day 1n=4 Participants	-1.9	5.54
Plasma ABeta 1-42: Prodromal: DB Week 24n=8 Participants	15.9	17.15
Plasma ABeta 1-42: Prodromal: DB Week 52n=6 Participants	5.1	17.68
Double-blind Treatment Phase(Period 1): Atabecestat, 25 mgPlasma ABeta 1-38: Prodromal: DB Day 1n=3 Participants	-6.6	13.56
Plasma ABeta 1-40: Asymptomatic at Risk: DB Day 1n=4 Participants	4.7	40.27
Plasma ABeta 1-40:Asymptomatic at Risk: DB Week 24n=4 Participants	-82.6	5.59
Plasma ABeta 1-40:Asymptomatic at Risk: DB Week 52n=4 Participants	-80.8	7.60
Plasma ABeta 1-40: Prodromal: DB Day 1n=7 Participants	-24.2	41.31
Plasma ABeta 1-40: Prodromal: DB Week 24n=14 Participants	-82.5	7.38
Plasma ABeta 1-40: Prodromal: DB Week 52n=13 Participants	-75.3	22.15
Double-blind Treatment Phase (Period 1): Atabecestat 10 mgPlasma ABeta 1-40: Asymptomatic at Risk: DB Day 1n=1 Participants	-4.9	NA
Plasma ABeta 1-40:Asymptomatic at Risk: DB Week 24n=4 Participants	-75.2	10.16
Plasma ABeta 1-40:Asymptomatic at Risk: DB Week 52n=4 Participants	-74.9	6.76
Plasma ABeta 1-40: Prodromal: DB Day 1n=3 Participants	25.8	66.03
Plasma ABeta 1-40: Prodromal: DB Week 24n=16 Participants	-68.6	8.20
Plasma ABeta 1-40: Prodromal: DB Week 52n=15 Participants	-70.9	9.24

Tau biomarkers

2 endpoints

Secondary/protocol endpoint

Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level

Time frame:Baseline, DB Day 1 and DB Week 52

percent change from baseline, improvement

Secondary/registry result

Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level

Time frame:Baseline, DB Day 1 and DB Week 52

percent change from baseline, improvement

Posted result

Group	Value (mean), Percent change	Standard deviation
Double-blind Treatment Phase (Period 1): PlaceboCSF Tau Protein: Asymptomatic at Risk: DB Week 52n=4 Participants	-1.4	14.10
CSF Tau Protein: Prodromal: DB Day 1n=3 Participants	6.1	6.82
CSF Tau Protein: Prodromal: DB Week 52n=12 Participants	13.6	45.55
CSF p-Tau Protein: Asymptomatic at Risk:DB Week 52n=4 Participants	-4.6	6.47
CSF p-Tau Protein: Prodromal: DB Day 1n=3 Participants	-0.6	7.81
CSF p-Tau Protein: Prodromal: Week 52n=12 Participants	2.2	12.93
Double-blind Treatment Phase (Period 1): Atabecestat 10 mgCSF Tau Protein: Asymptomatic at Risk: DB Week 52n=3 Participants	3.2	15.04
CSF Tau Protein: Prodromal: DB Week 52n=9 Participants	2.1	13.82
CSF p-Tau Protein: Asymptomatic at Risk:DB Week 52n=3 Participants	-4.9	1.40
CSF p-Tau Protein: Prodromal: Week 52n=9 Participants	-2.7	10.52
Double-blind Treatment Phase(Period 1): Atabecestat, 25 mgCSF Tau Protein: Asymptomatic at Risk: DB Week 52n=1 Participants	22.4	NA
CSF Tau Protein: Prodromal: DB Week 52n=11 Participants	1.4	8.20
CSF p-Tau Protein: Asymptomatic at Risk:DB Week 52n=1 Participants	8.3	NA
CSF p-Tau Protein: Prodromal: Week 52n=11 Participants	-2.6	8.52

Safety / tolerability / PK

2 endpoints

Primary/protocol endpoint

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

Time frame:Up to 3 years

event count, event

Primary/registry result

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

Time frame:Up to 3 years

event count, event

Posted result

Group	Value (number), Participants	Reported bounds
Double-blind Treatment Phase (Period 1): PlaceboNumber of Participants with TEAEsn=35 Participants	22	-
Number of Participants with Serious TEAEsn=35 Participants	3	-
Double-blind Treatment Phase (Period 1): Atabecestat 10 mgNumber of Participants with TEAEsn=29 Participants	15	-
Number of Participants with Serious TEAEsn=29 Participants	4	-
Double-blind Treatment Phase(Period 1): Atabecestat, 25 mgNumber of Participants with TEAEsn=26 Participants	21	-
Number of Participants with Serious TEAEsn=26 Participants	4	-
Open-label (OL) Phase (Period 2): Placebo to Atabecestat 5 mgNumber of Participants with TEAEsn=15 Participants	10	-
Number of Participants with Serious TEAEsn=15 Participants	2	-
OL Phase (Period 2): Placebo to Atabecestat 25 mgNumber of Participants with TEAEsn=14 Participants	11	-
Number of Participants with Serious TEAEsn=14 Participants	4	-
OL Phase (Period 2): Atabecestat 10 mg to Atabecestat 5 mgNumber of Participants with TEAEsn=26 Participants	19	-
Number of Participants with Serious TEAEsn=26 Participants	0	-
OL Phase (Period 2): Atabecestat 25 mg to Atabecestat 25 mgNumber of Participants with TEAEsn=22 Participants	16	-
Number of Participants with Serious TEAEsn=22 Participants	1	-

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

Novak G, Streffer JR, Timmers M, Henley D, Brashear HR, Bogert J, Russu A, Janssens L, Tesseur I, Tritsmans L, Van Nueten L, Engelborghs S. Long-term safety and tolerability of atabecestat (JNJ-54861911), an oral BACE1 inhibitor, in early Alzheimer's disease spectrum patients: a randomized, double-blind, placebo-controlled study and a two-period extension study. Alzheimers Res Ther. 2020 May 14;12(1):58. doi: 10.1186/s13195-020-00614-5.
PMID32410694via 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.