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

Phase 3TerminatedNCT02569398

Janssen Research & Development, LLC557 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

557

Conditions

Asymptomatic Amyloid-positive

Interventions

Atabecestat, 5 mgDRUG

One atabecestat, 5 mg tablet orally once daily up to 54 months.

Atabecestat, 25 mgDRUG

One atabecestat, 25 mg tablet orally once daily up to 54 months.

PlaceboDRUG

One matching placebo tablet orally once daily up to 54 months.

Eligibility

Sex: ALLMin age: 60 YearsMax age: 85 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Locations (128)

Outcomes

Primary Outcomes

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

PACC has 4 components: Free and Cued Selective Reminding Test (0 (worst)-48 (best recall); Delayed Paragraph Recall test (Range 0 (worst)-25 (best recall); Wechsler Adult Intelligence scale: (ranges 0 \[none\]-135 \[best performance\]) and Mini Mental State Examination (Range 0 \[worst\] - 30 \[best performance\]). Component scores are transformed using an established normalization method into z-scores. Each of 4 component change scores is divided by baseline sample standard deviation (SD) of that component. These z scores are summed to form the composite score. Thus, a change of 1 baseline standard deviation on each component would correspond to a 4-point change on the composite. A z-score of 0 is equal to the mean and implies how many SD higher or lower score as compared with baseline score, with increase signifying improvement.

Time frame: Baseline and Endpoint (Month 24)

Secondary Outcomes

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

The CFI is a modified version of the Mail-in Cognitive Function Screening Instrument, a participant- and informant-reported outcome measure developed by the Alzheimer's Disease Cooperative Study (ADCS). This assessment includes 15 questions (14 of which contribute to the total score, and 1 additional unscored item) that assess the participant's perceived ability to perform high-level functional tasks in daily-life and sense of overall cognitive functional ability. Study participants and their informants independently rate the participant's abilities. A participant-reported and an informant-reported total score is calculated which ranges from 0 to 14 (yes=1; no=0; maybe=0.5 for each question) with higher scores indicating greater impairment.

Time frame: Baseline and Endpoint (Month 24)

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

The Alzheimer's Disease Cooperative Study - Activities of Daily Living -Prevention Instrument (ADCS-ADLPI) is a functional measure composed of 18 items that includes 15 activities of daily living rated on a 4-point scale and 3 high level function items. Study participants and their informants independently rate the participant's level of ability (with no difficulty = 3, with some difficulty = 2, with a lot of difficulty = 1, did not do/don't know = 0). Informants are additionally asked to evaluate whether activities were completed less often, required more time to complete, and if any errors were made performing the task. High-level function items are rated as "yes" or "no". The scores range from 0 to 45 with higher scores indicating less impairment. The total score is the sum of the scores of the 15 activities of daily living questions (range: 0-45) with higher scores indicating less impairment.

Data from ClinicalTrials.gov

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