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

Janssen (J&J Innovative Medicine)

Status and phase: Terminated; Phase 3; Phase 2

Conditions: Asymptomatic Amyloid-positive

Treatments: Drug: Atabecestat, 25 mg; Drug: Atabecestat, 5 mg; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02569398

54861911ALZ2003 (Other Identifier)

2015-000948-42 (EudraCT Number)

CR107373

Details and patient eligibility

About

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.

Full 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.

Enrollment: 557 patients

Sex: All

Ages: 60 to 85 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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557 participants in 3 patient groups

Group 1

Experimental group

Description:

Participants will receive one atabecestat, 5 milligram (mg) tablet orally once daily up to 54 months.

Treatment:

Drug: Atabecestat, 5 mg

Group 2

Experimental group

Description:

Participants will receive one atabecestat, 25 mg tablet orally once daily up to 54 months.

Treatment:

Drug: Atabecestat, 25 mg

Group 3

Experimental group

Description:

Participants will receive one matching placebo tablet orally once daily up to 54 months.

Treatment:

Drug: Placebo