An Extension Study to Evaluate the Long-Term Safety and T... | NCT02406027 | Trialant
NCT02406027
Sponsor
Janssen Research & Development, LLC
Status
Terminated
Last Update Posted
Apr 29, 2025Actual
Enrollment
90Actual
Phase
Phase 2
Conditions
Alzheimer Disease
Interventions
JNJ-54861911, 10 mg
JNJ-54861911, 25 mg
Placebo
JNJ-54861911, 5 mg
Countries
Belgium
France
Germany
Netherlands
Spain
Sweden
Protocol Section
Identification Module
NCT ID
NCT02406027
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CR106978
Secondary IDs
ID
Type
Description
Link
54861911ALZ2004
Other Identifier
Janssen Research & Development, LLC
2014-004274-41
EudraCT Number
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
Acronym
Not provided
Organization
Janssen Research & Development, LLCINDUSTRY
Status Module
Record Verification Date
Apr 2025
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jul 2, 2015Actual
Primary Completion Date
Jun 28, 2018Actual
Completion Date
Jun 28, 2018Actual
First Submitted Date
Mar 27, 2015
First Submission Date that Met QC Criteria
Mar 27, 2015
First Posted Date
Apr 1, 2015Estimated
Results Waived
Not provided
Results First Submitted Date
Jun 25, 2019
Results First Submitted that Met QC Criteria
Sep 5, 2019
Results First Posted Date
Sep 9, 2019Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Apr 25, 2025
Last Update Posted Date
Apr 29, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Janssen Research & Development, LLCINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
Conditions Module
Conditions
Alzheimer Disease
Keywords
Alzheimer's Disease
JNJ-54861911
Placebo
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
90Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
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
Interventions
Name
Type
Description
Arm Group Labels
Other Names
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
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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.
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).
Other Outcomes
Not provided
Eligibility Module
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)
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
50 Years
Maximum Age
85 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Janssen Research & Development, LLC Clinical Trial
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.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
Participants who completed their treatment period as described under the parent protocol in study 54861911ALZ2002 (NCT02260674) or any ongoing/future Phase 1b or Phase 2 atabecestat clinical study were enrolled in this study.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Double-blind Treatment Phase (Period 1): Placebo
Participants received placebo matched to atabecestat orally, once daily from Day 1 up to Week 52 in the Double-blind treatment 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.
Drug: JNJ-54861911, 25 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
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
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).
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
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).
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
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).
Baseline, DB Day 1 and DB Week 52
Hoboken
Belgium
Montpellier
France
Paris
France
Toulouse
France
Essen
Germany
Homburg
Germany
Lübeck
Germany
Tübingen
Germany
Ulm
Germany
Amsterdam
Netherlands
Barcelona
Spain
Madrid
Spain
Terrasa Barcelona
Spain
Valencia
Spain
Mölndal
Sweden
Stockholm
Sweden
Participants received 10 milligram (mg) of atabecestat orally, once daily from Day 1 up to Week 52 in the Double-blind treatment phase.
Participants received 25 mg of atabecestat orally, once daily from Day 1 up to Week 52 in the Double-blind treatment phase.
FG003
Open-label (OL) Phase (Period 2): Placebo to Atabecestat 5 mg
Participants who were receiving placebo in the Double-blind treatment phase, received 5 mg atabecestat orally, once daily until registration of atabecestat or any safety issue in Open-label phase.
FG004
OL Phase (Period 2): Placebo to Atabecestat 25 mg
Participants who were receiving placebo in the Double-blind treatment phase, received 25 mg atabecestat orally, once daily until registration of atabecestat or any safety issue in Open-label phase.
FG005
OL Phase (Period 2): Atabecestat 10 mg to Atabecestat 5 mg
Participants who were receiving atabecestat 10 mg in the Double-blind treatment phase, received 5 mg atabecestat orally, once daily until registration of atabecestat or any safety issue in Open-label phase.
FG006
OL Phase (Period 2): Atabecestat 25 mg to Atabecestat 25 mg
Participants who were receiving atabecestat 25 mg in the Double-blind treatment phase continued to receive 25 mg atabecestat orally, once daily until registration of atabecestat or any safety issue in Open-label phase.
FG00035 subjects
FG00129 subjects
FG00226 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
Asymptomatic at Risk
FG0006 subjects
FG0018 subjects
FG0026 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
Prodromal
FG00029 subjects
FG00121 subjects
FG00220 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
COMPLETED
FG00029 subjects
FG00126 subjects
FG00222 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
NOT COMPLETED
FG0006 subjects
FG0013 subjects
FG0024 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0012 subjects
FG0021 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
Physician Decision
FG0003 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0002 subjects
FG0011 subjects
FG0021 subjects
FG0030 subjects
FG004
Subject Refused Further Study Treatment
FG0001 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Open-label Phase (Period 2)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00315 subjects
FG00414 subjects
FG00526 subjects
FG00622 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00315 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Double-blind safety analysis set included all participants who received study treatment during period 1.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Double-blind Treatment Phase (Period 1): Placebo
Participants received placebo matched to atabecestat orally, once daily from Day 1 up to Week 52 in the Double-blind treatment phase.
Participants received 25 mg of atabecestat orally, once daily from Day 1 up to Week 52 in the Double-blind treatment phase.
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00035
BG00129
BG00226
BG00390
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00070.4± 5.15
BG00171.4± 7.04
BG00267.9± 8.87
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00019
BG00116
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0012
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Hispanic or Latino
Title
Measurements
BG0000
BG0012
BG002
Region of Enrollment
Count of Participants
Participants
Title
Denominators
Categories
BELGIUM
Title
Measurements
BG0006
BG0014
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
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.
Safety analysis set included all participants who received at least 1 dose of study drug in the study (during Period 1 and 2).
Posted
Number
Participants
Up to 3 years
ID
Title
Description
OG000
Double-blind Treatment Phase (Period 1): Placebo
Participants received placebo matched to atabecestat orally, once daily from Day 1 up to Week 52 in the Double-blind treatment phase.
Participants received 25 mg of atabecestat orally, once daily from Day 1 up to Week 52 in the Double-blind treatment phase.
OG003
Open-label (OL) Phase (Period 2): Placebo to Atabecestat 5 mg
Participants who were receiving placebo in the Double-blind treatment phase, received 5 mg atabecestat orally, once daily until registration of atabecestat or any safety issue in Open-label phase.
OG004
OL Phase (Period 2): Placebo to Atabecestat 25 mg
Participants who were receiving placebo in the Double-blind treatment phase, received 25 mg atabecestat orally, once daily until registration of atabecestat or any safety issue in Open-label phase.
OG005
OL Phase (Period 2): Atabecestat 10 mg to Atabecestat 5 mg
Participants who were receiving atabecestat 10 mg in the Double-blind treatment phase, received 5 mg atabecestat orally, once daily until registration of atabecestat or any safety issue in Open-label phase.
OG006
OL Phase (Period 2): Atabecestat 25 mg to Atabecestat 25 mg
Participants who were receiving atabecestat 25 mg in the Double-blind treatment phase continued to receive 25 mg atabecestat orally, once daily until registration of atabecestat or any safety issue in Open-label phase.
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).
The Double-blind (DB) Safety Analysis Set included all participants (asymptomatic at risk and prodromal at baseline) who received study treatment during Period 1. Here 'n' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure at a given time point.
Posted
Mean
Standard Deviation
Percent change
Baseline, Double-blind (DB) Day 1 and DB Week 52
ID
Title
Description
OG000
Double-blind Treatment Phase (Period 1): Placebo
Participants received placebo matched to atabecestat orally, once daily from Day 1 up to Week 52 in the Double-blind treatment phase.
Secondary
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).
The Double-blind (DB) Safety Analysis Set included all participants (asymptomatic at risk and prodromal at baseline) who received study treatment during Period 1. Here 'n' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure at a given time point.
Posted
Mean
Standard Deviation
Percent change
Baseline, DB Day 1 and DB Week 52
ID
Title
Description
OG000
Double-blind Treatment Phase (Period 1): Placebo
Participants received placebo matched to atabecestat orally, once daily from Day 1 up to Week 52 in the Double-blind treatment phase.
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).
The Double-blind (DB) Safety Analysis Set included all participants (asymptomatic at risk and prodromal at baseline) who received study treatment during Period 1. Here 'n' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure at a given time point.
Posted
Mean
Standard Deviation
Percent change
Baseline, DB Day 1, DB Week 24, and DB Week 52
ID
Title
Description
OG000
Double-blind Treatment Phase (Period 1): Placebo
Participants received placebo matched to atabecestat orally, once daily from Day 1 up to Week 52 in the Double-blind treatment phase.
Secondary
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).
The Double-blind (DB) Safety Analysis Set included all participants (asymptomatic at risk and prodromal at baseline) who received study treatment during Period 1. Here 'n' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure at a given time point.
Posted
Mean
Standard Deviation
Percent change
Baseline, DB Day 1 and DB Week 52
ID
Title
Description
OG000
Double-blind Treatment Phase (Period 1): Placebo
Participants received placebo matched to atabecestat orally, once daily from Day 1 up to Week 52 in the Double-blind treatment phase.
Participants received 25 mg of atabecestat orally, once daily from Day 1 up to Week 52 in the Double-blind treatment phase.
0
26
4
26
14
26
EG003
Open-label (OL) Phase (Period 2): Placebo to Atabecestat 5 mg
Participants who were receiving placebo in the Double-blind treatment phase, received 5 mg atabecestat orally, once daily until registration of atabecestat or any safety issue in Open-label phase.
0
15
2
15
10
15
EG004
OL Phase (Period 2): Placebo to Atabecestat 25 mg
Participants who were receiving placebo in the Double-blind treatment phase, received 25 mg atabecestat orally, once daily until registration of atabecestat or any safety issue in Open-label phase.
0
14
4
14
11
14
EG005
OL Phase (Period 2): Atabecestat 10 mg to Atabecestat 5 mg
Participants who were receiving atabecestat 10 mg in the Double-blind treatment phase, received 5 mg atabecestat orally, once daily until registration of atabecestat or any safety issue in Open-label phase.
0
26
0
26
12
26
EG006
OL Phase (Period 2): Atabecestat 25 mg to Atabecestat 25 mg
Participants who were receiving atabecestat 25 mg in the Double-blind treatment phase continued to receive 25 mg atabecestat orally, once daily until registration of atabecestat or any safety issue in Open-label phase.
0
22
1
22
11
22
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Myocardial Ischaemia
Cardiac disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG0030 affected15 at risk
EG0040 affected14 at risk
EG0050 affected26 at risk
EG0061 affected22 at risk
Bronchitis
Infections and infestations
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0021 affected26 at risk
EG003
Pneumonia
Infections and infestations
MedDRA Version 21.0
Non-systematic Assessment
EG0001 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Pyelonephritis
Infections and infestations
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Burns Third Degree
Injury, poisoning and procedural complications
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0021 affected26 at risk
EG003
Craniocerebral Injury
Injury, poisoning and procedural complications
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0021 affected26 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA Version 21.0
Non-systematic Assessment
EG0001 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Thoracic Vertebral Fracture
Injury, poisoning and procedural complications
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0011 affected29 at risk
EG0020 affected26 at risk
EG003
Wrist Fracture
Injury, poisoning and procedural complications
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Hepatic Enzyme Increased
Investigations
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0021 affected26 at risk
EG003
Transaminases Increased
Investigations
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0011 affected29 at risk
EG0020 affected26 at risk
EG003
Foot Deformity
Musculoskeletal and connective tissue disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0001 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Psychotic Disorder
Psychiatric disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Calculus Urinary
Renal and urinary disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0011 affected29 at risk
EG0020 affected26 at risk
EG003
Renal Colic
Renal and urinary disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0011 affected29 at risk
EG0020 affected26 at risk
EG003
Ureteric Obstruction
Renal and urinary disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0011 affected29 at risk
EG0020 affected26 at risk
EG003
Menorrhagia
Reproductive system and breast disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0011 affected29 at risk
EG0020 affected26 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Ear Discomfort
Ear and labyrinth disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG0031 affected15 at risk
EG0040 affected14 at risk
EG0050 affected26 at risk
EG0060 affected22 at risk
Cataract
Eye disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0006 affected35 at risk
EG0010 affected29 at risk
EG0022 affected26 at risk
EG003
Dry Eye
Eye disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Eye Pruritus
Eye disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Keratitis
Eye disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0001 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Lacrimation Increased
Eye disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Macular Fibrosis
Eye disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Vitreous Floaters
Eye disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0001 affected35 at risk
EG0011 affected29 at risk
EG0021 affected26 at risk
EG003
Diverticulum Intestinal
Gastrointestinal disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Gastrooesophageal Reflux Disease
Gastrointestinal disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Inguinal Hernia
Gastrointestinal disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0001 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Asthenia
General disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Malaise
General disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0012 affected29 at risk
EG0020 affected26 at risk
EG003
Abscess Neck
Infections and infestations
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Bacterial Blepharitis
Infections and infestations
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Bronchitis
Infections and infestations
MedDRA Version 21.0
Non-systematic Assessment
EG0001 affected35 at risk
EG0011 affected29 at risk
EG0022 affected26 at risk
EG003
Candida Infection
Infections and infestations
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Cystitis
Infections and infestations
MedDRA Version 21.0
Non-systematic Assessment
EG0001 affected35 at risk
EG0011 affected29 at risk
EG0020 affected26 at risk
EG003
Dermatophytosis of Nail
Infections and infestations
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Gastroenteritis Viral
Infections and infestations
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Influenza
Infections and infestations
MedDRA Version 21.0
Non-systematic Assessment
EG0001 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA Version 21.0
Non-systematic Assessment
EG0002 affected35 at risk
EG0012 affected29 at risk
EG0022 affected26 at risk
EG003
Pneumonia
Infections and infestations
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Upper Respiratory Tract Infection
Infections and infestations
MedDRA Version 21.0
Non-systematic Assessment
EG0001 affected35 at risk
EG0010 affected29 at risk
EG0022 affected26 at risk
EG003
Urinary Tract Infection
Infections and infestations
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0021 affected26 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA Version 21.0
Non-systematic Assessment
EG0001 affected35 at risk
EG0012 affected29 at risk
EG0020 affected26 at risk
EG003
Periorbital Haemorrhage
Injury, poisoning and procedural complications
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Tendon Rupture
Injury, poisoning and procedural complications
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0021 affected26 at risk
EG003
Alanine Aminotransferase Increased
Investigations
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Hepatic Enzyme Increased
Investigations
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0021 affected26 at risk
EG003
Intraocular Pressure Increased
Investigations
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Transaminases Increased
Investigations
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0012 affected29 at risk
EG0020 affected26 at risk
EG003
Weight Decreased
Investigations
MedDRA Version 21.0
Non-systematic Assessment
EG0001 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Back Pain
Musculoskeletal and connective tissue disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0011 affected29 at risk
EG0021 affected26 at risk
EG003
Muscle Spasms
Musculoskeletal and connective tissue disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0001 affected35 at risk
EG0011 affected29 at risk
EG0020 affected26 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0001 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Basal Cell Carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA Version 21.0
Non-systematic Assessment
EG0001 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Skin Papilloma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0021 affected26 at risk
EG003
Squamous Cell Carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Complex Regional Pain Syndrome
Nervous system disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Headache
Nervous system disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0001 affected35 at risk
EG0010 affected29 at risk
EG0021 affected26 at risk
EG003
Tension Headache
Nervous system disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Confusional State
Psychiatric disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0001 affected35 at risk
EG0010 affected29 at risk
EG0021 affected26 at risk
EG003
Delirium
Psychiatric disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Depression
Psychiatric disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0021 affected26 at risk
EG003
Depressive Symptom
Psychiatric disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0012 affected29 at risk
EG0020 affected26 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0022 affected26 at risk
EG003
Nightmare
Psychiatric disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0001 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Oropharyngeal Pain
Respiratory, thoracic and mediastinal disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0011 affected29 at risk
EG0020 affected26 at risk
EG003
Actinic Keratosis
Skin and subcutaneous tissue disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0001 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0011 affected29 at risk
EG0021 affected26 at risk
EG003
Hair Colour Changes
Skin and subcutaneous tissue disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0002 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Nail Discolouration
Skin and subcutaneous tissue disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0001 affected35 at risk
EG0011 affected29 at risk
EG0021 affected26 at risk
EG003
Seborrhoeic Dermatitis
Skin and subcutaneous tissue disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0002 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
Hypertension
Vascular disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0002 affected35 at risk
EG0011 affected29 at risk
EG0020 affected26 at risk
EG003
Hypotension
Vascular disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0011 affected29 at risk
EG0020 affected26 at risk
EG003
Orthostatic Hypotension
Vascular disorders
MedDRA Version 21.0
Non-systematic Assessment
EG0000 affected35 at risk
EG0010 affected29 at risk
EG0020 affected26 at risk
EG003
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.
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.