E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Alzheimer's Disease (AD) is a neurodegenerative disease associated with aging. AD patients suffer from cognition deficits and memory loss as well as behavioral problems such as anxiety. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
E.1.2 | System Organ Class | 100000004852 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
- 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 |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title and Objective: Characterization of T-cell Response in Subjects Previously Treated with JNJ-54861911
Date and Version: 19 Dec 2017 version 1
|
|
E.3 | Principal 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 ɛ4 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 Aβ1-42 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 Aβ1-42 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. |
|
E.4 | Principal 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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the change in the PACC score from baseline. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | 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 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
54 months for all endpoints except RBANS (51 months) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 57 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Canada |
Denmark |
Finland |
Germany |
Italy |
Japan |
Mexico |
Netherlands |
Spain |
Sweden |
Switzerland |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |