Trial Outcomes & Findings for An Efficacy and Safety Study of Atabecestat in Participants Who Are Asymptomatic at Risk for Developing Alzheimer's Dementia (NCT NCT02569398)

Last Updated: 2025-04-29

Results Overview

PACC has 4 components: Free and Cued Selective Reminding Test (0 (worst)-48 (best recall); Delayed Paragraph Recall test (Range 0 (worst)-25 (best recall); Wechsler Adult Intelligence scale: (ranges 0 \[none\]-135 \[best performance\]) and Mini Mental State Examination (Range 0 \[worst\] - 30 \[best performance\]). Component scores are transformed using an established normalization method into z-scores. Each of 4 component change scores is divided by baseline sample standard deviation (SD) of that component. These z scores are summed to form the composite score. Thus, a change of 1 baseline standard deviation on each component would correspond to a 4-point change on the composite. A z-score of 0 is equal to the mean and implies how many SD higher or lower score as compared with baseline score, with increase signifying improvement.

Recruitment status

TERMINATED

Study phase

PHASE2/PHASE3

Target enrollment

557 participants

Primary outcome timeframe

Baseline and Endpoint (Month 24)

Results posted on

2025-04-29

Participant Flow

Total of 557 participants were enrolled in study. Study was early terminated based on experience of significant elevations in liver enzymes in participants receiving JNJ-54861911 in this study and 54861911ALZ2004 (NCT02406027).

Participant milestones

Participant milestones
Measure	Placebo Participants received a single dose of JNJ-54861911 matching placebo tablet orally once daily for up to 24 months.	JNJ-54861911 (5 mg) Participants received a single dose of JNJ-54861911 5 milligram (mg) tablet orally once daily for up to 24 months (participants randomized to this group received JNJ-54861911 10 mg prior to protocol amendment 3 and continued to receive JNJ-54861911 5-mg tablets after implementation of protocol Amendment 3; dated: 02-Mar-2016).	JNJ-54861911 (25 mg) Participants received a single dose of JNJ-54861911 25 mg tablet orally once daily for up to 24 months.
Overall Study STARTED	185	189	183
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	185	189	183

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received a single dose of JNJ-54861911 matching placebo tablet orally once daily for up to 24 months.	JNJ-54861911 (5 mg) Participants received a single dose of JNJ-54861911 5 milligram (mg) tablet orally once daily for up to 24 months (participants randomized to this group received JNJ-54861911 10 mg prior to protocol amendment 3 and continued to receive JNJ-54861911 5-mg tablets after implementation of protocol Amendment 3; dated: 02-Mar-2016).	JNJ-54861911 (25 mg) Participants received a single dose of JNJ-54861911 25 mg tablet orally once daily for up to 24 months.
Overall Study Adverse Event	0	1	6
Overall Study Withdrawal by Subject	43	43	30
Overall Study Study terminated by sponsor	130	131	134
Overall Study Other	12	14	13

Baseline Characteristics

An Efficacy and Safety Study of Atabecestat in Participants Who Are Asymptomatic at Risk for Developing Alzheimer's Dementia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=185 Participants Participants received a single dose of JNJ-54861911 matching placebo tablet orally once daily for up to 24 months.	JNJ-54861911 (5 mg) n=189 Participants Participants received a single dose of JNJ-54861911 5 milligram (mg) tablet orally once daily for up to 24 months (participants randomized to this group received JNJ-54861911 10 mg prior to protocol amendment 3 and continued to receive JNJ-54861911 5-mg tablets after implementation of protocol Amendment 3; dated: 02-Mar-2016).	JNJ-54861911 (25 mg) n=183 Participants Participants received a single dose of JNJ-54861911 25 mg tablet orally once daily for up to 24 months.	Total n=557 Participants Total of all reporting groups
Age, Continuous	70.2 years STANDARD_DEVIATION 5.81 • n=5 Participants	70.6 years STANDARD_DEVIATION 5.26 • n=7 Participants	70.5 years STANDARD_DEVIATION 5.62 • n=5 Participants	70.4 years STANDARD_DEVIATION 5.56 • n=4 Participants
Sex: Female, Male Female	108 Participants n=5 Participants	116 Participants n=7 Participants	117 Participants n=5 Participants	341 Participants n=4 Participants
Sex: Female, Male Male	77 Participants n=5 Participants	73 Participants n=7 Participants	66 Participants n=5 Participants	216 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	21 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	176 Participants n=5 Participants	183 Participants n=7 Participants	176 Participants n=5 Participants	535 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Asian	12 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants	34 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	4 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	12 Participants n=4 Participants
Race/Ethnicity, Customized Other	5 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	11 Participants n=4 Participants
Race/Ethnicity, Customized White Non-Hispanic	162 Participants n=5 Participants	170 Participants n=7 Participants	163 Participants n=5 Participants	495 Participants n=4 Participants
Region of Enrollment AUSTRALIA	21 Participants n=5 Participants	21 Participants n=7 Participants	21 Participants n=5 Participants	63 Participants n=4 Participants
Region of Enrollment BELGIUM	9 Participants n=5 Participants	10 Participants n=7 Participants	9 Participants n=5 Participants	28 Participants n=4 Participants
Region of Enrollment CANADA	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Region of Enrollment DENMARK	20 Participants n=5 Participants	20 Participants n=7 Participants	20 Participants n=5 Participants	60 Participants n=4 Participants
Region of Enrollment FINLAND	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Region of Enrollment GERMANY	2 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants
Region of Enrollment ITALY	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Region of Enrollment JAPAN	11 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants	33 Participants n=4 Participants
Region of Enrollment MEXICO	4 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	9 Participants n=4 Participants
Region of Enrollment NETHERLANDS	10 Participants n=5 Participants	11 Participants n=7 Participants	10 Participants n=5 Participants	31 Participants n=4 Participants
Region of Enrollment SPAIN	9 Participants n=5 Participants	10 Participants n=7 Participants	9 Participants n=5 Participants	28 Participants n=4 Participants
Region of Enrollment SWEDEN	3 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants
Region of Enrollment UNITED KINGDOM	23 Participants n=5 Participants	22 Participants n=7 Participants	22 Participants n=5 Participants	67 Participants n=4 Participants
Region of Enrollment UNITED STATES	67 Participants n=5 Participants	67 Participants n=7 Participants	65 Participants n=5 Participants	199 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Endpoint (Month 24)

Population: Intent to treat (ITT) analysis set (all randomized participants) with participants in whom PACC change score is non-missing at greater than or equal to (\>=) 1 post-baseline time point.

Outcome measures

Outcome measures
Measure	Placebo n=74 Participants Participants received a single dose of JNJ-54861911 matching placebo tablet orally once daily for up to 24 months.	JNJ-54861911 (5 mg) n=73 Participants Participants received a single dose of JNJ-54861911 5 milligram (mg) tablet orally once daily for up to 24 months (participants randomized to this group received JNJ-54861911 10 mg prior to protocol amendment 3 and continued to receive JNJ-54861911 5-mg tablets after implementation of protocol Amendment 3; dated: 02-Mar-2016).	JNJ-54861911 (25 mg) n=64 Participants Participants received a single dose of JNJ-54861911 25 mg tablet orally once daily for up to 24 months.
Change From Baseline in Preclinical Alzheimer Cognitive Composite (PACC) Score at Endpoint (Month 24)	0.096 z-score Standard Deviation 1.7261	-0.417 z-score Standard Deviation 1.8372	-1.096 z-score Standard Deviation 1.7796

SECONDARY outcome

Timeframe: Baseline and Endpoint (Month 24)

Population: ITT analysis set included all randomized participants. Here 'N' (number of Participants Analyzed) indicates the number of participants analyzed at this outcome measure and 'n' (number analyzed) was defined as the number of participants evaluable at specified category.

The CFI is a modified version of the Mail-in Cognitive Function Screening Instrument, a participant- and informant-reported outcome measure developed by the Alzheimer's Disease Cooperative Study (ADCS). This assessment includes 15 questions (14 of which contribute to the total score, and 1 additional unscored item) that assess the participant's perceived ability to perform high-level functional tasks in daily-life and sense of overall cognitive functional ability. Study participants and their informants independently rate the participant's abilities. A participant-reported and an informant-reported total score is calculated which ranges from 0 to 14 (yes=1; no=0; maybe=0.5 for each question) with higher scores indicating greater impairment.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Participants received a single dose of JNJ-54861911 matching placebo tablet orally once daily for up to 24 months.	JNJ-54861911 (5 mg) n=27 Participants Participants received a single dose of JNJ-54861911 5 milligram (mg) tablet orally once daily for up to 24 months (participants randomized to this group received JNJ-54861911 10 mg prior to protocol amendment 3 and continued to receive JNJ-54861911 5-mg tablets after implementation of protocol Amendment 3; dated: 02-Mar-2016).	JNJ-54861911 (25 mg) n=26 Participants Participants received a single dose of JNJ-54861911 25 mg tablet orally once daily for up to 24 months.
Change From Baseline in Cognitive Function Index (CFI) Score at Endpoint (Month 24) Total CFI Participant score	-0.04 Score on a scale Standard Deviation 1.866	0.09 Score on a scale Standard Deviation 1.135	0.75 Score on a scale Standard Deviation 2.628
Change From Baseline in Cognitive Function Index (CFI) Score at Endpoint (Month 24) Total CFI Informant score	-0.22 Score on a scale Standard Deviation 1.660	0.30 Score on a scale Standard Deviation 1.469	0.88 Score on a scale Standard Deviation 2.475

SECONDARY outcome

Timeframe: Baseline and Endpoint (Month 24)

Population: ITT analysis set included all randomized participants. Here 'n' (number analyzed) was defined as the number of participants evaluable at specified category.

The Alzheimer's Disease Cooperative Study - Activities of Daily Living -Prevention Instrument (ADCS-ADLPI) is a functional measure composed of 18 items that includes 15 activities of daily living rated on a 4-point scale and 3 high level function items. Study participants and their informants independently rate the participant's level of ability (with no difficulty = 3, with some difficulty = 2, with a lot of difficulty = 1, did not do/don't know = 0). Informants are additionally asked to evaluate whether activities were completed less often, required more time to complete, and if any errors were made performing the task. High-level function items are rated as "yes" or "no". The scores range from 0 to 45 with higher scores indicating less impairment. The total score is the sum of the scores of the 15 activities of daily living questions (range: 0-45) with higher scores indicating less impairment.

Outcome measures

Outcome measures
Measure	Placebo n=185 Participants Participants received a single dose of JNJ-54861911 matching placebo tablet orally once daily for up to 24 months.	JNJ-54861911 (5 mg) n=189 Participants Participants received a single dose of JNJ-54861911 5 milligram (mg) tablet orally once daily for up to 24 months (participants randomized to this group received JNJ-54861911 10 mg prior to protocol amendment 3 and continued to receive JNJ-54861911 5-mg tablets after implementation of protocol Amendment 3; dated: 02-Mar-2016).	JNJ-54861911 (25 mg) n=183 Participants Participants received a single dose of JNJ-54861911 25 mg tablet orally once daily for up to 24 months.
Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Prevention Instrument (ADCS-ADLPI) Total Score at Endpoint (Month 24) Total ADL Participant score	-0.04 Score on a Scale Standard Deviation 2.975	0.35 Score on a Scale Standard Deviation 2.832	0.15 Score on a Scale Standard Deviation 2.834
Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Prevention Instrument (ADCS-ADLPI) Total Score at Endpoint (Month 24) Total ADL Informant score	0.26 Score on a Scale Standard Deviation 4.223	-0.12 Score on a Scale Standard Deviation 3.941	0.24 Score on a Scale Standard Deviation 4.085

SECONDARY outcome

Timeframe: Baseline and Endpoint (Month 24)

Population: ITT analysis set included all randomized participants. Here 'N' (Number of participants analyzed) was defined as the number of participants evaluable at this outcome measure.

RBANS is 20 to 25 minute battery developed for cognitive assessment, detection, and characterization of dementia. RBANS includes 12 subtests that measure following 5 indices: (1)Attention Index, composed of Digit Span and Coding; (2)Language Index, consisting of Picture Naming and Semantic Fluency subtests; (3)Visuospatial/Construction Index, made up of Figure Copy and Line Orientation subtests; (4)Immediate Memory Index, composed of List Learning and Story Memory subtests, and (5)Delayed Memory Index, consisting of List Recall, List Recognition, Story Recall, and Figure Recall subtests. Completion of RBANS yields 5 index scores based on participant performance on various subtests, as well as a composite Total Index score for battery. Total index scores range from 40 to 160, and are normalized to a mean of 100 and standard deviation (SD) of 15. Higher scores indicate less impairment.

Outcome measures

Outcome measures
Measure	Placebo n=124 Participants Participants received a single dose of JNJ-54861911 matching placebo tablet orally once daily for up to 24 months.	JNJ-54861911 (5 mg) n=121 Participants Participants received a single dose of JNJ-54861911 5 milligram (mg) tablet orally once daily for up to 24 months (participants randomized to this group received JNJ-54861911 10 mg prior to protocol amendment 3 and continued to receive JNJ-54861911 5-mg tablets after implementation of protocol Amendment 3; dated: 02-Mar-2016).	JNJ-54861911 (25 mg) n=114 Participants Participants received a single dose of JNJ-54861911 25 mg tablet orally once daily for up to 24 months.
Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Score at Endpoint (Month 24)	2.0 Score on a scale Standard Deviation 8.90	-0.9 Score on a scale Standard Deviation 7.79	-1.7 Score on a scale Standard Deviation 9.75

SECONDARY outcome

Timeframe: Baseline and Endpoint (Month 24)

Population: As the study was terminated early with lesser participants and lesser sample size, data for this endpoint was not collected and analyzed per change in planned analysis.

The CDR-SB is an interviewer administered scale and impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2 and severe = 3. The 6 individual category ratings, or "box scores", were added together to give the CDR-Sum of Boxes which ranges from 0-18. Higher score indicates severe impairment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Endpoint (Month 24)

Population: As the study was terminated early with lesser participants and lesser sample size, data for this endpoint was not collected and analyzed per change in planned analysis.

The Neuropsychological Assessment Battery Daily Living Tests (NABDLTs) Score represent a series of performance based measures covering 5 domains (Attention, Memory, Language, Spatial, and Executive function). These are valid, clinically meaningful measures that objectively assess functional deficits. Participant performance scores on NAB subtests are summed, and then normalized to yield an index score. Index scores can range from less than or equal to (\< =) 55 to greater than or equal to (\> =) 145, and are normalized to a mean of 100 and standard deviation of 15. Higher scores indicate less impairment.

Outcome measures

Outcome data not reported

Adverse Events

Placebo

Serious events: 9 serious events

Other events: 80 other events

Deaths: 0 deaths

JNJ-54861911 (5 mg)

Serious events: 18 serious events

Other events: 75 other events

Deaths: 0 deaths

JNJ-54861911 (25 mg)

Serious events: 26 serious events

Other events: 88 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=185 participants at risk Participants received a single dose of JNJ-54861911 matching placebo tablet orally once daily for up to 24 months.	JNJ-54861911 (5 mg) n=189 participants at risk Participants received a single dose of JNJ-54861911 5 milligram (mg) tablet orally once daily for up to 24 months (participants randomized to this group received JNJ-54861911 10 mg prior to protocol amendment 3 and continued to receive JNJ-54861911 5-mg tablets after implementation of protocol Amendment 3; dated: 02-Mar-2016).	JNJ-54861911 (25 mg) n=183 participants at risk Participants received a single dose of JNJ-54861911 25 mg tablet orally once daily for up to 24 months.
Gastrointestinal disorders Diarrhoea	3.8% 7/185 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	7.9% 15/189 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	15.3% 28/183 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.
General disorders Fatigue	1.6% 3/185 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	2.6% 5/189 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	6.0% 11/183 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.
Infections and infestations Nasopharyngitis	14.6% 27/185 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	10.1% 19/189 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	8.7% 16/183 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.
Infections and infestations Upper Respiratory Tract Infection	10.3% 19/185 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	7.4% 14/189 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	6.6% 12/183 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.
Infections and infestations Urinary Tract Infection	3.8% 7/185 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	4.2% 8/189 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	8.2% 15/183 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.
Investigations Alanine Aminotransferase Increased	4.9% 9/185 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	4.8% 9/189 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	7.7% 14/183 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.
Investigations Aspartate Aminotransferase Increased	4.3% 8/185 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	4.8% 9/189 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	6.6% 12/183 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.
Musculoskeletal and connective tissue disorders Back Pain	4.9% 9/185 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	5.8% 11/189 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	5.5% 10/183 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.
Nervous system disorders Headache	7.6% 14/185 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	6.3% 12/189 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	8.7% 16/183 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.
Psychiatric disorders Abnormal Dreams	0.54% 1/185 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	2.1% 4/189 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	6.0% 11/183 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.
Respiratory, thoracic and mediastinal disorders Cough	1.1% 2/185 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	6.3% 12/189 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.	3.3% 6/183 • Up to 24 months Safety analysis set included all randomized participants who have received at least one study medication.

Additional Information

Senior Director

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER