Efficacy and Safety Trial of JNJ-54861911 in Participants who are Asymptomatic At Risk for Developing Alzheimer’s Dementia

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2015-000948-42-SE
• Date of registration: 14/08/2015
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V.
• Public title: Efficacy and Safety Trial of JNJ-54861911 in Participants who are Asymptomatic At Risk for Developing Alzheimer’s Dementia
• Scientific 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
• Date of first enrolment: 14/12/2015
• Target sample size: 1650
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000948-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, Denmark, Finland, Germany, Italy, Japan, Mexico, Netherlands, Spain, Sweden, Switzerland, United Kingdom, United States

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen Pharmaceutica N.V.

• Name: Clinical Registry Group
• Affiliation: Janssen Pharmaceutica N.V.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subject must be a man or woman 60 to 85 years of age, inclusive, at time of informed consent. Subjects 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 APOE ?4 genotype
c. A previously known biomarker status demonstrating elevated amyloid accumulation in CSF or PET
2. Subjects must have a global CDR score of 0 at screening.
3. Subjects 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.
4. Subjects must have evidence of elevated amyloid accumulation by means of either:
a. Low CSF Aß1-42 levels at screening
b. A positive amyloid PET scan at screening (depending on the site’s PET capability)

Note: The cut off value for CSF Aß1-42 will be based on the value established by the central CSF screening laboratory and specified in a separate laboratory manual. Screening amyloid PET scans will be assessed centrally by a qualified reader for inclusion based on predefined criteria as documented in the imaging manual.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1400

Exclusion criteria:
1. Subject is receiving an acetylcholinesterase (AChE) inhibitor and/or memantine at any time during screening or Day 1 predose.
2. Subject has evidence of any brain disease other than potential very early signs of AD (eg, mild hippocampal atrophy) or typical age-related changes (eg, mild white matter hyperintensity on MRI). The screening MRI scan shall be interpreted by a local radiologist and a central radiologist for exclusionary findings prior to enrolling the subject. Both local and central interpretations shall be reviewed by the investigator; in case of disagreement, the central radiology report will be used to determine subject eligibility in consultation with the sponsor’s medical monitor.
3. Subject has any other abnormality that could cause a possible cognitive deficit (including, but not limited to vascular encephalopathy or large strokes [as imaged by cerebral MRI]).
4. Subject has any contraindications for MRI (eg, prostheses, implants, claustrophobia, pacemaker)
5. Subject has met criteria for dementia or has a brain disorder that can cause dementia.
6. Subject has evidence of familial autosomal dominant AD (mutation identified in the family and/or subject prior to randomization).
7. Subject has a history of or current thyroid disease or thyroid dysfunction, which is currently uncontrolled, unevaluated, or untreated. Subjects treated for thyroid disease may be enrolled following review of their diagnostic and treatment history records by the investigator and with written concurrence by the sponsor's medical monitor to ensure disease/treatment stability and compliance.
8. Subject has a vitamin B12 or folic acid deficiency. A low vitamin B12 level is exclusionary unless follow-up labs (homocysteine and methylmalonic acid) indicate that the value is not physiologically significant. Subjects treated with vitamin B12 or folic acid may be enrolled following review of their diagnostic and treatment history records by the investigator and with written concurrence by the sponsor's medical monitor to ensure disease/treatment stability and compliance.
9. Subject has chromosome 21 trisomy (Down syndrome).
10. Subject has a history within the past 2 years or current diagnosis of significant psychiatric illness, per the most current version of the Diagnostic and Statistical Manual of Mental Disorders (DSM) (including but not limited to major depressive disorders and anxiety disorders) (subjects who are symptom free or with minimal limited symptoms may be included); or the subject has a current diagnosis or history of schizophrenia or bipolar disorder.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Alzheimer's Disease
MedDRA version: 20.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: JNJ-54861911
Product Code: JNJ-54861911
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Atabecestat
CAS Number: 1200493-78-2
Current Sponsor code: JNJ-54861911
Other descriptive name: JNJ-54861911-AAA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: JNJ-54861911
Product Code: JNJ-54861911
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Atabecestat
CAS Number: 1200493-78-2
Current Sponsor code: JNJ-54861911
Other descriptive name: JNJ-54861911-AAA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: - Change from Baseline in Cognitive Function Index (CFI) to Month 54
- Change from Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living - Prevention Instrument (ADCS-ADL-PI) Total Score to Month 54
- Change from Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Score to Month 51
- Change from Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) Score to Month 54
- Change from Baseline in Neuropsychological Assessment Battery Daily Living Tests (NAB-DLTs) Score to Month 54
- Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
- Trough Plasma Concentration (Ctrough) of JNJ54861911
- Area Under the Plasma Concentration Time Curve from 0 to tau Hours After Dosing (AUCtau)
- Change in mean Cerebral Fibrillar Amyloid Accumulation
- Change from Baseline of Neurodegeneration by Assessing Changes in imaging Biomarkers

Main Objective: The primary objective of this study is to determine whether treatment with JNJ-54861911 slows cognitive decline compared with placebo treatment, as measured by a composite cognitive measure, the Preclinical Alzheimer Cognitive Composite (PACC), in amyloid-positive subjects who are asymptomatic at risk for developing Alzheimer's dementia.

Primary end point(s): The primary efficacy endpoint is the change in the PACC score from baseline.

Timepoint(s) of evaluation of this end point: 54 months

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 54 months for all endpoints except RBANS (51 months)

Secondary end point(s): • Change from baseline at Month 54 on CFI (total score)
• Change from baseline at Month 54 in ADCS-ADL-PI score (total score)
• Change from baseline at Month 51 on RBANS (total scale score)
• Change from baseline at Month 54 on CDR-SB
• Change from baseline at Month 54 on NAB-DLTs for Memory and Attention

Secondary ID(s)

54861911ALZ2003

Source(s) of Monetary Support

Janssen Research and Development, LLC

Ethics review

Status: Approved
Approval date:
Contact: