A Safety and Tolerability Study of JNJ-54861911 in Participants With Early Alzheimer's Disease

NCT02260674 | Completed Phase 2 DMC

• 3 other identifiers: CR10524054861911ALZ20022014-002159-24
• Study Type: interventional
• Target: 114
• Locations: 6 countries
• Sites: 19

Brief Summary

The purpose of this study is to evaluate the long-term safety and tolerability of JNJ-54861911 during 6 months of treatment in participants with early (predementia) alzheimer's disease (AD \[degenerative disease of the brain characterized by the insidious onset of dementia, impairment of memory, judgment, attention span, and problem solving skills are followed by severe apraxias and a global loss of cognitive abilities\]).

Conditions

Alzheimer's Disease

Keywords

Alzheimer's Disease; JNJ-54861911; Placebo

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)

  An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

  up to 10 months

Secondary Outcomes (7)

• Relationship Between Dose and Exposure of JNJ-54861911 With Safety

  Month 1 up to Month 6

• Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels and Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha, sAPP-beta), Total sAPP Levels

  Baseline and Month 6

• Percent Change From Baseline in Plasma ABeta 1-40 Levels and sAPP Fragments (sAPP-alpha, sAPP-beta), Total sAPP Levels

  Baseline and Month 6 (Day 168)

• Relationship Between Changes in CSF and Plasma ABeta Species and sAPP Fragments With Safety

  Month 1 up to Month 6

• Maximum Plasma Concentration (Cmax) of JNJ-54861911

  Pre-dose on Day 1, post-dose on Day 28, 56, 84, 112, 140 and 168

Study Arms (3)

Treatment Group 1

EXPERIMENTAL

Participants will self-administer JNJ-54861911, two tablets of 5 milligram (mg) each for a total of 10 mg, orally, once daily, from Day 1 until Month 6.

Drug: JNJ-54861911, 10 milligram (mg)

Treatment Group 2

EXPERIMENTAL

Participants will self-administer JNJ-54861911, two tablets of 25 mg each for a total of 50 mg, orally, once daily, from Day 1 until Month 6.

Drug: JNJ-54861911, 50 mg

Placebo

PLACEBO COMPARATOR

Placebo matched to JNJ-54861911, orally, once daily, from Day 1 until Month 6.

Drug: Placebo

Interventions

JNJ-54861911, 10 milligram (mg) DRUG

Participants will self-administer JNJ-54861911, two tablets of 5 mg each for a total of 10 mg, orally, once daily, from Day 1 until Month 6 in treatment group 1.

Treatment Group 1

JNJ-54861911, 50 mg DRUG

Participants will self-administer JNJ-54861911, two tablets of 25 mg each for a total of 50 mg, orally, once daily, from Day 1 until Month 6 in treatment group 2.

Treatment Group 2

Placebo DRUG

Placebo matched to JNJ-54861911, orally, once daily, from Day 1 until Month 6 in placebo group.

Placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants in the early alzheimer's disease (AD) spectrum must have a global Clinical Dementia Rating Scale( CDR) score of 0 (asymptomatic at risk for AD) to 0.5 prodromal AD (pAD) inclusive
• Participants must have evidence of amyloid pathology 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
• Participants must have a body mass index between 18 and 35 kilogram per square meter (kg/m\^2), inclusive, at screening
• Participants 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 ECG performed at screening or at baseline. If there are abnormalities, they must be consistent with the underlying illness in the study population and not a potential cause of cognitive impairment, with written concurrence with the sponsor's medical monitor

You may not qualify if:

• Participant has evidence of any brain disease, other than potential very early signs of AD (e.g. 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 strokes including lacuna's (as imaged by cerebral MRI) and Major Depression (as defined by most current Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria)
• Participant with history or presence of significant depression as defined by the most current DSM criteria
• Participant has a clinically significant abnormal physical- or neurological examination, vital signs at screening or baseline (Day 1 predose)
• Participant has a history of or current liver or renal insufficiency; clinically significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, hematologic, rheumatologic, psychiatric, or metabolic disturbances (e.g. unstable situation needing monitoring or regular dose adaptations)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (19)

Unknown Facility

Ghent, Belgium

Location

Unknown Facility

Hoboken, Belgium

Location

Unknown Facility

Montpellier, France

Location

Unknown Facility

Paris, France

Location

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Toulouse, France

Location

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Essen, Germany

Location

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Halle, Germany

Location

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Hamburg, Germany

Location

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Homburg, Germany

Location

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Lübeck, Germany

Location

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Tübingen, Germany

Location

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Ulm, Germany

Location

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Amsterdam, Netherlands

Location

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Barcelona, Spain

Location

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Madrid, Spain

Location

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Terrasa Barcelona N/A, Spain

Location

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Valencia, Spain

Location

Unknown Facility

Mölndal, Sweden

Location

Unknown Facility

Stockholm, Sweden

Location

Related Publications (1)

• 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.

  PMID: 32410694 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

atabecestat

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2014
• First Posted: October 9, 2014
• Study Start: November 1, 2014
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: April 29, 2025

Record last verified: 2025-04

Locations

NL (1); SE (2); FR (3); ES (4); BE (2); DE (7)