Clinical trial NCT02260674: A Safety and Tolerability Study of JNJ-54861911 in Participants With Early Alzheimer's Disease
Official title: A Phase 2a Randomized, Double-blind, Placebo-Controlled, Parallel-Group, Multi-center Study Investigating the Safety and Tolerability of JNJ-54861911 in Subjects With Early Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Keywords: Alzheimer's Disease
JNJ-54861911
Placebo
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2014-10-09
Enrollment: 114
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the long-term safety and tolerability of JNJ-54861911 during 6 months of treatment in participants with early (predementia) alzheimer's disease (AD \[degenerative disease of the brain characterized by the insidious onset of dementia, impairment of memory, judgment, attention span, and problem solving skills are followed by severe apraxias and a global loss of cognitive abilities\]).

Detailed description: This is a double-blind (neither the researchers nor the participants know what treatment the participant is receiving), placebo-controlled (an inactive substance; a pretend treatment \[with no drug in it\] that is compared in a clinical trial with a drug to test if the drug has a real effect), randomized (study drug assigned by chance), multi-center (when more than one hospital or medical school team work on a medical research study), parallel-group study. The study consists of 3 Parts; Screening Phase of 90 days, double-blind Treatment Phase of 6 months and Follow-up Phase of 7 to 28 days following the last dose in Month 6. Eligible participants in the early (predementia) AD spectrum will be randomized to either Treatment group 1, 2 or placebo and participants who previously participated in study 54861911ALZ1005 will be enrolled in this study and will receive the same treatment as in study 54861911ALZ1005. The study duration for each participant will be approximately 10 months. Blood and cerebrospinal fluid (CSF) samples will be collected to evaluate the plasma pharmacokinetics of JNJ-54861911, as well as amyloid beta fragments. Participants' safety will be monitored throughout the study, including magnetic resonance imaging (MRI) and cognitive measures.

Eligibility criteria: Inclusion Criteria:

* Participants in the early alzheimer's disease (AD) spectrum must have a global Clinical Dementia Rating Scale( CDR) score of 0 (asymptomatic at risk for AD) to 0.5 prodromal AD (pAD) inclusive
* Participants must have evidence of amyloid pathology 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
* Participants must have a body mass index between 18 and 35 kilogram per square meter (kg/m\^2), inclusive, at screening
* Participants 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 ECG performed at screening or at baseline. If there are abnormalities, they must be consistent with the underlying illness in the study population and not a potential cause of cognitive impairment, with written concurrence with the sponsor's medical monitor
* Before randomization, a woman must be not of childbearing potential: postmenopausal (greater than or equal to \[\>=\] 50 years of age with amenorrhea for at least 12 months; permanently sterilized \[e.g., tubal occlusion, hysterectomy, bilateral salpingectomy\]); or otherwise be incapable of pregnancy. In case of questionable status qualified personal of the sponsor should be consulted to decide on the potential for inclusion of the participant

Exclusion Criteria:

* Participant has evidence of any brain disease, other than potential very early signs of AD (e.g. 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 strokes including lacuna's (as imaged by cerebral MRI) and Major Depression (as defined by most current Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria)
* Participant has evidence of familial autosomal dominant AD. (Inclusion can be made upon written confirmation by sponsor, when the mutation is known and deemed not to be modulating Beta-secretase \[BACE\] cleavage)
* Participant with history or presence of significant depression as defined by the most current DSM criteria
* Participant has a clinically significant abnormal physical- or neurological examination, vital signs at screening or baseline (Day 1 predose)
* Participant has a history of or current liver or renal insufficiency; clinically significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, hematologic, rheumatologic, psychiatric, or metabolic disturbances (e.g. unstable situation needing monitoring or regular dose adaptations)

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: up to 10 months
Secondary outcomes:
measure: Relationship Between Dose and Exposure of JNJ-54861911 With Safety
timeFrame: Month 1 up to Month 6
measure: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels and Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha, sAPP-beta), Total sAPP Levels
timeFrame: Baseline and Month 6
measure: Percent Change From Baseline in Plasma ABeta 1-40 Levels and sAPP Fragments (sAPP-alpha, sAPP-beta), Total sAPP Levels
timeFrame: Baseline and Month 6 (Day 168)
measure: Relationship Between Changes in CSF and Plasma ABeta Species and sAPP Fragments With Safety
timeFrame: Month 1 up to Month 6
measure: Maximum Plasma Concentration (Cmax) of JNJ-54861911
timeFrame: Pre-dose on Day 1, post-dose on Day 28, 56, 84, 112, 140 and 168
measure: Time to Reach the Maximum Plasma or CSF concentration (Tmax)
timeFrame: Pre-dose on Day 1, post-dose on Day 28, 56, 84, 112, 140 and 168
measure: Area Under the Plasma/CSF Concentration-time Curve From Time 0 to tau Hours Post Dosing (AUCtau)
timeFrame: Pre-dose on Day 1, post-dose on Day 28, 56, 84, 112, 140 and 168
Other outcomes:
Locations:
city: Gent
country: Belgium
city: Hoboken
country: Belgium
city: Montpellier Cedex 5
country: France
city: Paris
country: France
city: Toulouse
country: France
city: Essen
country: Germany
city: Halle
country: Germany
city: Hamburg N/A
country: Germany
city: Homburg
country: Germany
city: Luebeck
country: Germany
city: Tübingen
country: Germany
city: Ulm
country: Germany
city: Amsterdam
country: Netherlands
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Terrasa Barcelona N/A
country: Spain
city: Valencia
country: Spain
city: Mölndal
country: Sweden
city: Stockholm
country: Sweden
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Novak G, Streffer JR, Timmers M, Henley D, Brashear HR, Bogert J, Russu A, Janssens L, Tesseur I, Tritsmans L, Van Nueten L, Engelborghs S. Long-term safety and tolerability of atabecestat (JNJ-54861911), an oral BACE1 inhibitor, in early Alzheimer's disease spectrum patients: a randomized, double-blind, placebo-controlled study and a two-period extension study. Alzheimers Res Ther. 2020 May 14;12(1):58. doi: 10.1186/s13195-020-00614-5.