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

Primary Purpose

Alzheimer Disease

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

JNJ-54861911, 10 mg

JNJ-54861911, 25 mg

Placebo

JNJ-54861911, 5 mg

About this trial

This is an interventional treatment trial for Alzheimer Disease focused on measuring Alzheimer's Disease, JNJ-54861911, Placebo

Eligibility Criteria

50 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Participants in the early Alzheimer's disease (AD) spectrum at time of enrollment under the parent protocol and according to its inclusion and exclusion criteria, must have very recently completed their treatment in a Phase 1b or Phase 2 JNJ-54861911 clinical study (example [e.g.], 54861911ALZ2002) under the parent protocol. Enrollment in this study should be completed (Day 1 of double-blind [DB] treatment phase) as soon as possible, but within 6 weeks, following completion of their treatment period under the parent protocol. If not defined under the parent protocol, completion of the treatment period is defined as having completed all study related procedures of the last visit of the treatment period under the parent protocol. A screening phase of up to 12 weeks may be allowed following written approval of the Sponsor
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

Exclusion Criteria:

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)

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Placebo Comparator

Active Comparator

Arm Label

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

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

Double-blind Treatment Phase: Placebo

Open-label Phase: JNJ-54861911, 5 mg

Open-label Phase: JNJ-54861911, 25 mg

Arm Description

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

CSF samples were obtained for measuring levels of different ABeta fragments such as ABeta 1-37, ABeta 1-38, ABeta 1-40, and ABeta 1-42. ABeta fragments of different length produced by cleavage of amyloid precursor protein (APP) by beta-secretase (BACE) and gamma-secretase complex in brain and excreted into CSF. Participants were classified as asymptomatic at risk: cognitively and functionally normal (Clinical Dementia Rating Scale score [CDR] =0), but with biomarker pattern consistent with early stage AD (preclinical stage); and prodromal: had some limited cognitive impairment (CDR =0.5), and still functionally normal, with biomarker pattern consistent with early stage (predementia) AD, but had as of yet no dementia (predementia stage). Here, 'Number analyzed=0' signifies that either CSF concentration was below lower limit of quantification for assay or sample was collected under parent study 54861911ALZ2002 (NCT02260674).

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

The CSF samples were obtained for measuring levels of different soluble amyloid precursor protein (sAPP) fragments (sAPP-alpha, sAPP-beta). Participants were classified as asymptomatic at risk: cognitively and functionally normal (CDR score =0), but with biomarker pattern consistent with early stage alzheimer's disease (AD) (preclinical stage); and prodromal: had some limited cognitive impairment (CDR =0.5), and still functionally normal, with biomarker pattern consistent with early stage (predementia) AD, but had as of yet no dementia (predementia stage). Here, 'Number analyzed=0' signifies that either CSF concentration was below lower limit of quantification for assay or sample was collected under parent study 54861911ALZ2002 (NCT02260674).

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

Plasma samples were obtained for measuring levels of different ABeta fragments such as ABeta 1-38, ABeta 1-40, ABeta 1-42. ABeta fragments of different length were produced by cleavage of APP by beta-secretase (BACE) and gamma-secretase complex in different peripheral tissues, including white blood cells and were measured in plasma. Participants classified as asymptomatic at risk: cognitively and functionally normal (CDR score =0), but with biomarker pattern consistent with early stage AD (preclinical stage); and prodromal: had some limited cognitive impairment (CDR =0.5), and still functionally normal, with biomarker pattern consistent with early stage (predementia) AD, but had as of yet no dementia (predementia stage). Here, 'Number analyzed=0' signifies that either CSF concentration was below lower limit of quantification for assay or sample was collected under parent study 54861911ALZ2002 (NCT02260674).

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

The CSF samples were obtained for measuring levels of Tau protein and phosphorylated (p)-tau protein. Participants were classified as asymptomatic at risk: cognitively and functionally normal (CDR score =0), but with biomarker pattern consistent with early stage AD (preclinical stage); and prodromal: had some limited cognitive impairment (CDR =0.5), and still functionally normal, with biomarker pattern consistent with early stage (predementia) AD, but had as of yet no dementia (predementia stage). Here, 'Number analyzed=0' signifies that either CSF concentration was below lower limit of quantification for assay or sample was collected under parent study 54861911ALZ2002 (NCT02260674).

Full Information

NCT ID

NCT02406027

First Posted

March 27, 2015

Last Updated

June 1, 2023

Sponsor

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT02406027

Brief Title

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

Official Title

A Randomized, Two-Period, Double-Blind Placebo-Controlled and Open-Label, Multicenter Extension Study to Determine the Long-Term Safety and Tolerability of JNJ-54861911 in Subjects in the Early Alzheimer's Disease Spectrum

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Terminated

Study Start Date

July 2, 2015 (Actual)

Primary Completion Date

June 28, 2018 (Actual)

Study Completion Date

June 28, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

Participants in the early Alzheimer's Disease (AD) spectrum, enrolled in ongoing or future clinical trials with JNJ-54861911 (Phase 1b or Phase 2 studies) will be provided the opportunity to participate in this study upon completion of their treatment period under the parent protocol. The study will consist of a Screening phase and 2 sequential treatment phases (a 12-month double-blind [DB] treatment phase [placebo controlled] and an open-label [OL] phase [active]) followed by an End-of-Treatment visit. Treatment in OL phase will continue until registration of JNJ-54861911; unless safety issues emerge as determined by the Data Review Committee (DRC) that would warrant termination of the study. Blood and cerebrospinal fluid (CSF) samples will be collected to evaluate the plasma and CSF pharmacokinetics of JNJ-54861911, as well as amyloid beta fragments. Participants' safety will be monitored throughout the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer Disease

Keywords

Alzheimer's Disease, JNJ-54861911, Placebo

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

90 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

Double-blind Treatment Phase: Placebo

Arm Type

Placebo Comparator

Arm Description

Arm Title

Open-label Phase: JNJ-54861911, 5 mg

Arm Type

Active Comparator

Arm Description

Arm Title

Open-label Phase: JNJ-54861911, 25 mg

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

JNJ-54861911, 10 mg

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

JNJ-54861911, 25 mg

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

JNJ-54861911, 5 mg

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Up to 3 years

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

Baseline, DB Day 1 and DB Week 52

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

Baseline, DB Day 1 and DB Week 52

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Participants in the early Alzheimer's disease (AD) spectrum at time of enrollment under the parent protocol and according to its inclusion and exclusion criteria, must have very recently completed their treatment in a Phase 1b or Phase 2 JNJ-54861911 clinical study (example [e.g.], 54861911ALZ2002) under the parent protocol. Enrollment in this study should be completed (Day 1 of double-blind [DB] treatment phase) as soon as possible, but within 6 weeks, following completion of their treatment period under the parent protocol. If not defined under the parent protocol, completion of the treatment period is defined as having completed all study related procedures of the last visit of the treatment period under the parent protocol. A screening phase of up to 12 weeks may be allowed following written approval of the Sponsor 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 Exclusion Criteria: 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen Research & Development, LLC Clinical Trial

Organizational Affiliation

Janssen Research & Development, LLC

Official's Role

Study Chair

Facility Information:

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

Homburg

Country

Germany

City

Luebeck

Country

Germany

City

Tubingen

Country

Germany

City

Ulm

Country

Germany

City

Amsterdam

Country

Netherlands

City

Barcelona

Country

Spain

City

Madrid

Country

Spain

City

Terrasa Barcelona

Country

Spain

City

Valencia

Country

Spain

City

Mölndal

Country

Sweden

City

Stockholm

Country

Sweden

12. IPD Sharing Statement

Citations:

PubMed Identifier

32410694

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.

Results Reference

derived

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

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