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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02569398
Recruitment Status : Completed
First Posted : October 6, 2015
Last Update Posted : January 21, 2019
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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.

Condition or disease Intervention/treatment Phase
Asymptomatic Amyloid-positive Drug: Atabecestat, 5 mg Drug: Atabecestat, 25 mg Drug: Placebo Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 596 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : October 29, 2015
Actual Primary Completion Date : December 20, 2018
Actual Study Completion Date : December 20, 2018

Arm Intervention/treatment
Experimental: Group 1
Participants will receive one atabecestat, 5 milligram (mg) tablet orally once daily up to 54 months.
Drug: Atabecestat, 5 mg
One atabecestat, 5 mg tablet orally once daily up to 54 months.

Experimental: Group 2
Participants will receive one atabecestat, 25 mg tablet orally once daily up to 54 months.
Drug: Atabecestat, 25 mg
One atabecestat, 25 mg tablet orally once daily up to 54 months.

Experimental: Group 3
Participants will receive one matching placebo tablet orally once daily up to 54 months.
Drug: Placebo
One matching placebo tablet orally once daily up to 54 months.

Primary Outcome Measures :
  1. Change from Baseline in Preclinical Alzheimer Cognitive Composite (PACC) to Month 54 [ Time Frame: Up to Month 54 ]
    The PACC is composed of 4 measures [Free and Cued Selective Reminding Test, Delayed Paragraph Recall, Wechsler Adult Intelligence Scale (WAIS)-IV Coding and Mini Mental State Examination (MMSE) Total Score] that are weighted towards episodic memory and includes a timed executive function test and a global cognitive screening test. Each component score will be transformed into z scores. These z-scores will then be summed to form the composite. Higher scores indicate better performance.

Secondary Outcome Measures :
  1. Change from Baseline in Cognitive Function Index (CFI) to Month 54 [ Time Frame: Up to Month 54 ]
    Cognitive Function Index (CFI) is a 15 point rating scale that assess the Participants perceived ability to perform high-level functional tasks in daily-life and sense of overall cognitive functional ability. The higher scores indicates greater impairment.

  2. Change from Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Prevention Instrument (ADCS-ADLPI) Total Score to Month 54 [ Time Frame: Up to Month 54 ]
    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. The scores range from 0 to 45 with higher scores indicating less impairment.

  3. Change from Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Score to Month 51 [ Time Frame: Up to Month 51 ]

    The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) rating scale is used to assess the cognitive assessment, detection, and characterization of dementia. The scores range from 40 to 160, and are normalized to a mean of 100 and standard deviation of 15.

    Higher scores indicating less impairment.

  4. Change from Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score to Month 54 [ Time Frame: Up to Month 54 ]
    The Clinical Dementia Rating - Sum of Boxes (CDR-SB) scores ranging from 0 to 18. The CDR assesses 3 domains of cognition (memory, orientation, judgment/problem solving) and 3 domains of function (community affairs, home/hobbies, personal care) using semistructured interviews of both the study participant and an informant carried out by a trained rater. The Higher CDR-SB scores indicate greater impairment.

  5. Change from Baseline in Neuropsychological Assessment Battery Daily Living Tests (NABDLTs) Score to Month 54 [ Time Frame: Up to Month 54 ]
    The Neuropsychological Assessment Battery Daily Living Tests (NABDLTs) Score represent a series of performance based measures covering 5 domains (Attention, Memory, Language, Spatial, and Executive function). Index scores can range from less than or equal to (< =) 55 to greater than or equal to (> =) 145, and are normalized to a mean of 100 and standard deviation of 15. Higher scores indicate less impairment.

  6. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Month 58 ]
    An AE was any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

  7. Trough Plasma Concentration (Ctrough) of Atabecestat [ Time Frame: Up to Month 54 ]
    The Ctrough is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen.

  8. Area Under the Plasma Concentration-Time Curve From 0 to tau Hours After Dosing (AUCtau) [ Time Frame: Up to Month 54 ]
    The AUCtau is the area under the plasma concentration-time curve from time zero to tau hours (time tau is the dosing interval).

  9. Change in mean Cerebral Fibrillar Amyloid Accumulation [ Time Frame: Up to Month 54 ]
    The accumulation of cerebral fibrillar amyloid will be measured by amyloid positron emission tomography (PET) imaging.

  10. Change From Baseline of Neurodegeneration by Assessing Changes in Imaging Biomarkers [ Time Frame: Up to Month 54 ]
    Neurodegeneration will be assessed based on changes in imaging biomarkers.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   60 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02569398

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Sponsors and Collaborators
Janssen Research & Development, LLC
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

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Responsible Party: Janssen Research & Development, LLC Identifier: NCT02569398     History of Changes
Other Study ID Numbers: CR107373
2015-000948-42 ( EudraCT Number )
54861911ALZ2003 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: October 6, 2015    Key Record Dates
Last Update Posted: January 21, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Research & Development, LLC:
Alzheimer disease

Additional relevant MeSH terms:
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Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Neurodegenerative Diseases