Clinical trial NCT02360657: Study Investigating the Effects of JNJ-54861911 on Amyloid-beta Processing in Cerebrospinal Fluid (CSF) and Plasma in Japanese Participants Asymptomatic at Risk for Alzheimer Dementia
Official title: A Double-blind, Placebo-controlled, Randomized, 4-Week, Multiple-dose, Proof of Mechanism (POM) Study in Japanese Subjects Asymptomatic at Risk for Alzheimer Dementia (ARAD) Investigating the Effects of JNJ-54861911 on A-beta Processing in Cerebrospinal Fluid (CSF) and Plasma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease
Keywords: Alzheimer's Disease
Alzheimer Dementia
JNJ-54861911
Beta Secretase Inhibitor
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2015-02-10
Enrollment: 18
Sex: ALL
Minimum age (years): 65
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety, tolerability and effect of JNJ-54861911 on level of amyloid-beta in Cerebrospinal Fluid (CSF) and plasma following 4 weeks of treatment in Japanese participants asymptomatic at risk for Alzheimer Dementia (ARAD) at the intended target dose range.

Detailed description: This is a multi-center (when more than one hospital or medical school team work on a medical research study), double-blind (neither physician nor participant knows the treatment that the participant receives), placebo-controlled (the experimental treatment or procedure is compared to an inactive substance), randomized (study medication assigned by chance), multiple dose, Proof of Mechanism (POM) study in Japanese participants ARAD. All eligible participants will be randomly assigned to 1 of 3 treatment groups (that is, placebo, JNJ-54861911 10 milligram \[mg\] or JNJ-54861911 50 mg once daily regimen). This study will consist of Screening Phase (8-week), Double blind Treatment Phase (4-week), and Follow-up Phase (2-week). The maximum study duration for a participant will be 14 weeks. Participant's safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Participant must have had sufficient education or work experience to exclude mental retardation based on Diagnostic and Statistical Manual of Mental Disorders 4th edition, Text Revision (DSM-IV-TR) and must be able to read and write and must have adequate hearing and visual acuity to complete the required psychometric tests
* Participant must have a Clinical Dementia Rating Scale- Japanese version (CDR-J) score of '0' and as such rated as normal
* Participant must have evidence of amyloid deposition as demonstrated by low Cerebrospinal Fluid (CSF) Amyloid (A)-beta 1-42 levels at Screening
* Participant must have a body mass index between 18 and 35 kilogram per square meter, inclusive, at Screening
* 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 has evidence of any brain disease other than potential very early signs of Alzheimer's disease (AD) or typical age related changes, or any other abnormality that could explain a possible cognitive deficit
* Participant has been diagnosed with dementia due to AD, due to other diseases, or with AD and contribution of other disorders (mixed dementia)
* Participant has evidence of familial autosomal dominant AD
* Participant has any contra-indications for Magnetic Resonance Imaging (MRI) (for example, prostheses, implants, claustrophobia, pacemakers, and others)
* Participant has a clinically significant abnormal physical- or neurological examination, vital signs or 12-lead ECG (including QTc greater than 450 millisecond for males and females, left bundle branch block, atrio-ventricular \[AV\] block second degree or higher, permanent pacemaker or implantable cardioverter defibrillator \[ICD\]) at Screening or Baseline, which in the opinion of the investigator is not appropriate and reasonable for the population under study

Primary outcomes:
measure: Levels of Amyloid (A)-beta1-40 in Cerebrospinal Fluid (CSF) After Treatment at the Intended Target Dose Range
timeFrame: Up to 4 weeks
measure: Levels of A-beta1-40 in Plasma After Treatment at the Intended Target Dose Range
timeFrame: Up to 4 weeks
measure: Maximum Observed Plasma Concentration (Cmax) of JNJ 54861911
timeFrame: Up to 4 weeks
measure: Minimum Observed Plasma Concentration (Cmin) of JNJ 54861911
timeFrame: Up to 4 weeks
measure: Time to Reach Maximum Observed Concentration (Tmax) of JNJ 54861911
timeFrame: Up to 4 weeks
measure: Area Under the Curve From Time Zero to end of Dosing Interval (AUCtau)
timeFrame: Up to 4 weeks
measure: Cerebrospinal Fluid Exposure of JNJ-54861911
timeFrame: Up to 4 weeks
measure: The Number of Participants who Experienced Adverse Events as a Measure of Safety and Tolerability of JNJ-54861911 After Multiple-Dose Administration in the Anticipated Target Dose Range
timeFrame: Up to 4 weeks
Secondary outcomes:
measure: Levels of A-beta Fragments (A-beta1-37, A-beta1-38, and A-beta1-42) in CSF After Treatment at the Intended Target Dose Range
timeFrame: Up to 4 weeks
measure: Levels of A-beta Fragments (A-beta1-37, A-beta1-38, and A-beta1-42) in Plasma After Treatment at the Intended Target Dose Range
timeFrame: Up to 4 weeks
measure: Levels of Soluble Amyloid Precursor Protein (APP) Fragments in CSF (sAPP-alpha, sAPP-beta, totalAPP) After Treatment at the Intended Target Dose Range
timeFrame: Up to 4 weeks
measure: Compare the Relationship of A-beta1-40 Levels in Plasma and CSF After Treatment at the Intended Dose Range
timeFrame: Up to 4 weeks
Other outcomes:
Locations:
city: Fukuoka
country: Japan
city: Tokyo
country: Japan
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K., Japan Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Timmers M, Streffer JR, Russu A, Tominaga Y, Shimizu H, Shiraishi A, Tatikola K, Smekens P, Borjesson-Hanson A, Andreasen N, Matias-Guiu J, Baquero M, Boada M, Tesseur I, Tritsmans L, Van Nueten L, Engelborghs S. Pharmacodynamics of atabecestat (JNJ-54861911), an oral BACE1 inhibitor in patients with early Alzheimer's disease: randomized, double-blind, placebo-controlled study. Alzheimers Res Ther. 2018 Aug 23;10(1):85. doi: 10.1186/s13195-018-0415-6.