A Safety and Tolerability Study of JNJ-54861911 in Participants With Early Alzheimer's Disease

NCT ID: NCT02260674

Last Updated: 2025-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 114 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30
• Study Completion Date: 2016-06-30

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.

Conditions

Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Treatment Group 1

Participants will self-administer JNJ-54861911, two tablets of 5 milligram (mg) each for a total of 10 mg, orally, once daily, from Day 1 until Month 6.

Group Type: EXPERIMENTAL

JNJ-54861911, 10 milligram (mg)

Intervention Type: DRUG

Participants will self-administer JNJ-54861911, two tablets of 5 mg each for a total of 10 mg, orally, once daily, from Day 1 until Month 6 in treatment group 1.

Treatment Group 2

Participants will self-administer JNJ-54861911, two tablets of 25 mg each for a total of 50 mg, orally, once daily, from Day 1 until Month 6.

Group Type: EXPERIMENTAL

JNJ-54861911, 50 mg

Intervention Type: DRUG

Participants will self-administer JNJ-54861911, two tablets of 25 mg each for a total of 50 mg, orally, once daily, from Day 1 until Month 6 in treatment group 2.

Placebo

Placebo matched to JNJ-54861911, orally, once daily, from Day 1 until Month 6.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo matched to JNJ-54861911, orally, once daily, from Day 1 until Month 6 in placebo group.

Interventions

JNJ-54861911, 10 milligram (mg)

Participants will self-administer JNJ-54861911, two tablets of 5 mg each for a total of 10 mg, orally, once daily, from Day 1 until Month 6 in treatment group 1.

Intervention Type: DRUG

JNJ-54861911, 50 mg

Participants will self-administer JNJ-54861911, two tablets of 25 mg each for a total of 50 mg, orally, once daily, from Day 1 until Month 6 in treatment group 2.

Intervention Type: DRUG

Placebo

Placebo matched to JNJ-54861911, orally, once daily, from Day 1 until Month 6 in placebo group.

Intervention Type: DRUG

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)

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Ghent, , Belgium

Hoboken, , Belgium

Montpellier, , France

Paris, , France

Toulouse, , France

Essen, , Germany

Halle, , Germany

Hamburg, , Germany

Homburg, , Germany

Lübeck, , Germany

Tübingen, , Germany

Ulm, , Germany

Amsterdam, , Netherlands

Barcelona, , Spain

Madrid, , Spain

Terrasa Barcelona N/A, , Spain

Valencia, , Spain

Mölndal, , Sweden

Stockholm, , Sweden

Countries

Belgium; France; Germany; Netherlands; Spain; Sweden

References

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.

Reference Type: DERIVED

PMID: 32410694 (View on PubMed)

Other Identifiers

54861911ALZ2002

Identifier Type: OTHER

Identifier Source: secondary_id

2014-002159-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR105240

Identifier Type: -

Identifier Source: org_study_id