An Extension Study to Evaluate the Long-Term Safety and Tolerability of JNJ-54861911 in Participants in the Early Alzheimer's Disease Spectrum

NCT02406027 | Terminated Phase 2 Results DMC

• 3 other identifiers: CR10697854861911ALZ20042014-004274-41
• Study Type: interventional
• Target: 90
• Locations: 6 countries
• Sites: 17

Brief Summary

The purpose of this study is to evaluate the long-term safety and tolerability of JNJ-54861911 in participants in the early Alzheimer's disease (AD \[progressive brain disease that slowly destroys memory and thinking skills, and eventually even the ability to carry out the simplest tasks\]) spectrum that have completed a Phase 1b or Phase 2 clinical trial with JNJ-54861911, who are willing to continue their assigned treatment.

Conditions

Alzheimer Disease

Keywords

Alzheimer's Disease; JNJ-54861911; Placebo

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

  An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events between administration of study drug and up to 3 years that were absent before treatment or that worsened relative to pre-treatment state. An serious adverse event (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 3 years

Secondary Outcomes (4)

• Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels

  Baseline, Double-blind (DB) Day 1 and DB Week 52

• Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels

  Baseline, DB Day 1 and DB Week 52

• Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels

  Baseline, DB Day 1, DB Week 24, and DB Week 52

• Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level

  Baseline, DB Day 1 and DB Week 52

Study Arms (5)

Double-blind Treatment Phase: JNJ-54861911, 10 mg

EXPERIMENTAL

Participants will continue with their current treatment regimen (10 milligram \[mg\] of JNJ-54861911) established in the parent study of JNJ-54861911. Participants will receive 10 milligram (mg) of JNJ-54861911 orally, once daily from Day 1 up Week 52 in the DB treatment phase.

Drug: JNJ-54861911, 10 mg

Double-blind Treatment Phase: JNJ-54861911, 25 mg

EXPERIMENTAL

Participants will continue with their current treatment regimen (25 mg of JNJ-54861911) established in the parent study of JNJ-54861911. Participants will receive 25 mg of JNJ-54861911 orally, once daily from Day 1 up Week 52 in the DB treatment phase.

Drug: JNJ-54861911, 25 mg

Double-blind Treatment Phase: Placebo

PLACEBO COMPARATOR

Participants will continue with their current treatment regimen established in the parent study of JNJ-54861911. Participants will receive placebo matching to JNJ-54861911 orally, once daily from Day 1 up Week 52 in the DB treatment phase.

Drug: Placebo

Open-label Phase: JNJ-54861911, 5 mg

ACTIVE COMPARATOR

Participants who were receiving JNJ-54861911, 10 mg and placebo in the DB treatment phase, will receive the 5 mg JNJ-54861911 once daily up to end of treatment visit (until registration of JNJ-54861911 or any safety issue) in Open-label phase.

Drug: JNJ-54861911, 10 mg; Drug: JNJ-54861911, 5 mg

Open-label Phase: JNJ-54861911, 25 mg

ACTIVE COMPARATOR

Participants who were receiving JNJ-54861911, 25 mg in the DB treatment phase, will continue to receive the same regimen in open-label treatment phase. Participants who were receiving placebo in the DB treatment phase will be randomly assigned to receive 25 mg of JNJ-54861911 once daily up to end of treatment visit (until registration of JNJ-54861911 or any safety issue) in the open-label treatment phase.

Drug: JNJ-54861911, 25 mg

Interventions

JNJ-54861911, 10 mg DRUG

Participants will self-administer JNJ-54861911 tablet, 10 mg (2\*5 mg), orally, once daily.

Double-blind Treatment Phase: JNJ-54861911, 10 mg; Open-label Phase: JNJ-54861911, 5 mg

JNJ-54861911, 25 mg DRUG

Participants will self-administer 1 tablet of JNJ-54861911, containing 25 mg orally, once daily.

Double-blind Treatment Phase: JNJ-54861911, 25 mg; Open-label Phase: JNJ-54861911, 25 mg

Placebo DRUG

Participants will self administer placebo matching to JNJ-54861911 orally once daily.

Double-blind Treatment Phase: Placebo

JNJ-54861911, 5 mg DRUG

Participants will self-administer JNJ-54861911 tablet, 5 mg, orally, once daily.

Open-label Phase: JNJ-54861911, 5 mg

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Participant must be willing and able to adhere to the prohibitions and restrictions specified in this protocol
• Each Participants (or their legally acceptable representative and caregiver depending on disease state and local requirements) must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study
• Participants must have a reliable informant (relative, partner, or friend). The informant must be willing to participate as a source of information and has at least weekly contact with the participant (contact can be in-person, via telephone or other audio/visual communication). The informant must have sufficient contact such that the Investigator feels he/she can provide meaningful information about the participant's daily function. If possible, an alternate informant meeting these criteria who can replace the primary informant should be identified prior to randomization
• Any condition or situation which, in the opinion of the Investigator, may put the participant at significant risk, may confound the study results, or may interfere significantly with participant's participation in the study
• The use of concomitant medications known to prolong the QT/QTc interval
• Participant has a history of moderate or severe hepatic impairment or severe renal insufficiency unless completely resolved for more than a year. Participant has clinically significant ongoing hepatic, renal, cardiac, vascular, pulmonary, gastrointestinal, endocrine, hematologic, rheumatologic, psychiatric or metabolic conditions (e.g., requiring frequent monitoring or medication adjustments or is otherwise unstable)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (17)

Unknown Facility

Ghent, Belgium

Location

Unknown Facility

Hoboken, Belgium

Location

Unknown Facility

Montpellier, France

Location

Unknown Facility

Paris, France

Location

Unknown Facility

Toulouse, France

Location

Unknown Facility

Essen, Germany

Location

Unknown Facility

Homburg, Germany

Location

Unknown Facility

Lübeck, Germany

Location

Unknown Facility

Tübingen, Germany

Location

Unknown Facility

Ulm, Germany

Location

Unknown Facility

Amsterdam, Netherlands

Location

Unknown Facility

Barcelona, Spain

Location

Unknown Facility

Madrid, Spain

Location

Unknown Facility

Terrasa Barcelona, Spain

Location

Unknown Facility

Valencia, Spain

Location

Unknown Facility

Mölndal, Sweden

Location

Unknown Facility

Stockholm, Sweden

Location

Related Publications (1)

• 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.

  PMID: 32410694 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

atabecestat

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Limitations and Caveats

The major limitation of this study was early termination of the study/program by the sponsor, which resulted in small numbers of participants in groups, precluding meaningful interpretation of some of the analyses.

Results Point of Contact

• Title: Senior Director
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2015
• First Posted: April 1, 2015
• Study Start: July 2, 2015
• Primary Completion: June 28, 2018
• Study Completion: June 28, 2018
• Last Updated: April 29, 2025
• Results First Posted: September 9, 2019

Record last verified: 2025-04

Locations

FR (3); NL (1); DE (5); BE (2); ES (4); SE (2)