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

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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: JNJ-54861911, 10 mg; Drug: JNJ-54861911, 50 mg; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
  • Tokyo, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 85 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JNJ-54861911, 10 mg; JNJ-54861911, 10 milligram (mg) (2*5 mg tablet) orally once daily for 4 weeks.	Drug: JNJ-54861911, 10 mg; JNJ-54861911, 10 mg (2*5 mg tablet) orally once daily for 4 weeks.
Experimental: JNJ-54861911, 50 mg; JNJ-54861911, 50 mg (2*25 mg tablet) orally once daily for 4 weeks.	Drug: JNJ-54861911, 50 mg; JNJ-54861911, 50 mg (2*25 mg tablet) orally once daily for 4 weeks.
Placebo Comparator: Placebo; Placebo matching to JNJ-54861911 tablet orally once daily for 4 weeks.	Drug: Placebo; Placebo matching to JNJ-54861911 tablet orally once daily for 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of Amyloid (A)-beta1-40 in Cerebrospinal Fluid (CSF) After Treatment at the Intended Target Dose Range		Up to 4 weeks
Levels of A-beta1-40 in Plasma After Treatment at the Intended Target Dose Range		Up to 4 weeks
Maximum Observed Plasma Concentration (Cmax) of JNJ 54861911	The Cmax is the maximum observed plasma concentration.	Up to 4 weeks
Minimum Observed Plasma Concentration (Cmin) of JNJ 54861911	The Cmin is the minimum observed plasma concentration.	Up to 4 weeks
Time to Reach Maximum Observed Concentration (Tmax) of JNJ 54861911	The Tmax is time to reach the maximum observed plasma concentration.	Up to 4 weeks
Area Under the Curve From Time Zero to end of Dosing Interval (AUCtau)	The AUCtau is a measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.	Up to 4 weeks
Cerebrospinal Fluid Exposure of JNJ-54861911		Up to 4 weeks
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	An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is 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.	Up to 4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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	Up to 4 weeks
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	Up to 4 weeks
Levels of Soluble Amyloid Precursor Protein (APP) Fragments in CSF (sAPP-alpha, sAPP-beta, totalAPP) After Treatment at the Intended Target Dose Range	Up to 4 weeks
Compare the Relationship of A-beta1-40 Levels in Plasma and CSF After Treatment at the Intended Dose Range	Up to 4 weeks

Collaborators and Investigators

• Sponsor: Janssen Pharmaceutical K.K.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2015
• Primary Completion (Actual): September 8, 2015
• Study Completion (Actual): September 8, 2015

Study Registration Dates

• First Submitted: February 5, 2015
• First Submitted That Met QC Criteria: February 5, 2015
• First Posted (Estimate): February 10, 2015

Study Record Updates

• Last Update Posted (Actual): February 4, 2019
• Last Update Submitted That Met QC Criteria: January 31, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; JNJ-54861911; Alzheimer Dementia; Beta Secretase Inhibitor
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Tauopathies; Dementia; Alzheimer Disease
• Other Study ID Numbers: CR106397; 54861911ALZ1008 (Other Identifier: Janssen Pharmaceutical K.K., Japan)