Clinical trial NCT02569398: An Efficacy and Safety Study of Atabecestat in Participants Who Are Asymptomatic at Risk for Developing Alzheimer's Dementia
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Asymptomatic Amyloid-positive
Keywords: Alzheimer disease
Atabecestat
Dementia
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2015-10-06
Enrollment: 557
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Change From Baseline in Preclinical Alzheimer Cognitive Composite (PACC) Score at Endpoint (Month 24)
timeFrame: Baseline and Endpoint (Month 24)
Secondary outcomes:
measure: Change From Baseline in Cognitive Function Index (CFI) Score at Endpoint (Month 24)
timeFrame: Baseline and Endpoint (Month 24)
measure: Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Prevention Instrument (ADCS-ADLPI) Total Score at Endpoint (Month 24)
timeFrame: Baseline and Endpoint (Month 24)
measure: Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Score at Endpoint (Month 24)
timeFrame: Baseline and Endpoint (Month 24)
measure: Change From Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score at Endpoint (Month 24)
timeFrame: Baseline and Endpoint (Month 24)
measure: Change From Baseline in Neuropsychological Assessment Battery Daily Living Tests (NABDLTs) Score at Endpoint (Month 24)
timeFrame: Baseline and Endpoint (Month 24)
Other outcomes:
Locations:
city: Birmingham
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state: Alabama
city: Phoenix
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state: Arizona
city: Sun City
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state: Arizona
city: Downey
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state: California
city: La Jolla
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state: California
city: Newport Beach
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state: California
city: Orange
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state: California
city: San Diego
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state: California
city: New Haven
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state: Connecticut
city: Washington
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state: District of Columbia
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city: Orlando
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city: Ormond Beach
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state: Florida
city: Tampa
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state: Florida
city: The Villages
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state: Florida
city: Atlanta
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state: Georgia
city: Columbus
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state: Georgia
city: Decatur
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state: Georgia
city: Arlington Heights
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state: Illinois
city: Chicago
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city: Elk Grove Village
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city: Elkhart
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state: Indiana
city: Indianapolis
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city: Iowa City
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state: Iowa
city: Westwood
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state: Kansas
city: Lexington
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state: Kentucky
city: Baton Rouge
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state: Louisiana
city: Bangor
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state: Maine
city: Boston
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state: Massachusetts
city: Plymouth
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state: Massachusetts
city: Ann Arbor
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state: Michigan
city: Kalamazoo
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state: Michigan
city: Hattiesburg
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state: Mississippi
city: Saint Louis
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state: Missouri
city: Las Vegas
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state: Nevada
city: Amherst
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state: New York
city: New York
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state: New York
city: Orangeburg
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state: New York
city: Rochester
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city: Staten Island
country: United States
state: New York
city: Syracuse
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state: New York
city: Charlotte
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state: North Carolina
city: Raleigh
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state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Willow Grove
country: United States
state: Pennsylvania
city: Providence
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state: Rhode Island
city: Charleston
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state: South Carolina
city: Cordova
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state: Tennessee
city: Nashville
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state: Tennessee
city: Houston
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state: Texas
city: San Antonio
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state: Texas
city: Salt Lake City
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state: Utah
city: Charlottesville
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state: Virginia
city: Seattle
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state: Washington
city: Spokane
country: United States
state: Washington
city: Madison
country: United States
state: Wisconsin
city: Adelaide
country: Australia
city: Brisbane
country: Australia
city: Darlinghurst
country: Australia
city: East Gosford
country: Australia
city: Heidelberg
country: Australia
city: Herston
country: Australia
city: Subiaco
country: Australia
city: Tarren Point
country: Australia
city: Waratah
country: Australia
city: Antwerpen
country: Belgium
city: Baudour
country: Belgium
city: Brussel
country: Belgium
city: Edegem
country: Belgium
city: Liège
country: Belgium
city: Mons
country: Belgium
city: Toronto
country: Canada
state: Ontario
city: Gatineau
country: Canada
state: Quebec
city: Aalborg
country: Denmark
city: Ballerup
country: Denmark
city: København Ø
country: Denmark
city: Rødovre
country: Denmark
city: Kuopio N/a
country: Finland
city: Turku
country: Finland
city: Berlin
country: Germany
city: Essen
country: Germany
city: Halle
country: Germany
city: Homburg
country: Germany
city: Kiel
country: Germany
city: Mannheim
country: Germany
city: Mittweida
country: Germany
city: Stuttgart
country: Germany
city: ULM
country: Germany
city: Chiba-shi
country: Japan
city: Fukuoka-shi
country: Japan
city: Hachioji-shi
country: Japan
city: Iizuka-shi
country: Japan
city: Osaka-shi
country: Japan
city: Shibuya-ku
country: Japan
city: Shinjuku-ku
country: Japan
city: Shirakawa
country: Japan
city: Tokyo
country: Japan
city: Chihuahua
country: Mexico
city: Monterrey
country: Mexico
city: San Luis Potosi
country: Mexico
city: Tlalnepantla de Baz
country: Mexico
city: Amsterdam
country: Netherlands
city: Breda
country: Netherlands
city: s-Hertogenbosch
country: Netherlands
city: Utrecht
country: Netherlands
city: Barcelona
country: Spain
city: Getxo
country: Spain
city: Madrid
country: Spain
city: Manresa
country: Spain
city: San Sebastian
country: Spain
city: Terrassa
country: Spain
city: Valencia
country: Spain
city: Mölndal
country: Sweden
city: Birmingham
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Guildford
country: United Kingdom
city: London
country: United Kingdom
city: Newcastle upon Tyne
country: United Kingdom
city: Plymouth
country: United Kingdom
city: Swindon
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.