A Phase 2 interventional study of JNJ-63733657 and Placebo in Alzheimer Disease, Cognitive Dysfunction and Dementia, sponsored by Janssen Research & Development, LLC. Terminated at 122 sites in 10 countries. Open to participants aged 55 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-04-03.
Sponsored by Janssen Research & Development, LLC · Phase 2, Interventional, and Treatment
The primary purpose of this study is to evaluate the effect of JNJ-63733657 versus placebo on clinical decline as measured by the Integrated Alzheimer's Disease Rating Scale (iADRS), a composite of cognition and function.
3,678 studies on the registry are indexed under Alzheimer Disease; 872 are open to participants now.
This study's enrollment of 523 is above the median of 70 across 2,808 interventional studies indexed under Alzheimer Disease.
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Of its 278 completed or terminated interventional studies of FDA-regulated products, 131 (47%) have results posted.
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Exclusion Criteria:
Participants will receive single dose of JNJ-63733657 low-dose administered by intravenous (IV) infusion every 4 weeks during the double-blind treatment period. Participants will have an option to continue with the long-term extension (LTE) phase of the trial and will continue to receive the same treatment and dose during the LTE treatment period.
Drug: JNJ-63733657
Participants will receive single dose of JNJ-63733657 high-dose administered by IV infusion every 4 weeks during double-blind treatment period. Participants will have an option to continue with the LTE phase of the trial and will continue to receive the same treatment and dose during the LTE treatment period.
Drug: JNJ-63733657
Participants will receive single dose of matching placebo to JNJ-63733657 administered by IV infusion every 4 weeks during double-blind treatment period. Participants will have an option to continue with the LTE phase of the trial and will be re-randomized in a 1:1 ratio to receive either JNJ-63733657 low-dose or JNJ-63733657 high-dose during the LTE treatment period.
Drug: Placebo
JNJ-63733657 low or high dose will be administered by IV infusion.
Placebo matching to JNJ-63733657 will be administered by IV infusion.
Change From Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Total Score at Week 104
The linear combination of the ADAS Cog13 and ADCS ADL MCI that serves as a composite of cognition and function (overall clinical status) of the participant and score range from 0 to 138 with lower scores indicating worse performance. The iADRS will be a combination of ADAS Cog13 (score 0 to 85, higher scores indicate worse cognitive performance) and ADCS-ADL MCI (yielding a score 0 to 53, lower scores indicate worse daily function).
Time frame: Week 104
Change From Baseline in Alzheimer's Disease Assessment Scale Cognitive subscale 13-item version (ADAS-Cog 13) Total Score at Week 104
ADAS-Cog11 consists of 11 tasks measuring the disturbances of memory, language, praxis, attention, and other cognitive abilities. The modified ADAS-Cog 13 item scale includes all original ADAS-Cog items with the addition of a number cancellation task and a delayed free recall task, for a maximum total score of 85 points, with higher scores indicative of worse cognitive performance. Thus, a negative change from baseline represents improvement in cognition. Items are recorded on an electronic device which will provide the ADAS-Cog 13 total score.
Time frame: Week 104
Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living for Mild Cognitive Impairment (ADCS-ADL MCI) Total Score at Week 104
ADCS-ADL MCI is a functional measure based on information provided by the study partner (informant) that describes the performance of participants in several ADLs. It assesses 18 instrumental activities of daily living (higher level daily functions) and one basic daily function (dressing). Total score ranges from 0 to 53 with higher scores indicating less impairment.
Time frame: Week 104
Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Index Score at Week 88
The RBANS includes 12 subtests that are divided into 5 RBANS indices: 1-Immediate memory (List learning and story memory); 2-Visuospatial/constructional (figure copy and line orientation); 3-Language (picture naming and semantic fluency); 4-Attention (digit span and coding); 5-Delayed memory (list recall, list recognition, story memory, and figure recall) will be reported. Index scores are expressed as an age-adjusted standard score with a normal mean of 100 and an SD of 15. The sum of Index Scores is the sum of the 5 index scores, and the Sum of Index Scores is converted to an RBANS Total Scale Index Score via a mapping table. RBANS Total Scale Index Score is a norm-based t-score, based on a distribution with a mean of 100 and standard deviation (SD) of 15. Higher scores on each sub measure and index indicate better performance.
Time frame: Baseline, Week 88
Change From Baseline in RBANS Indices at Week 88
Change from baseline in RBANS indices will be assessed. The RBANS includes 12 subtests that are divided into 5 RBANS indices: 1-Immediate memory (List learning and story memory); 2-Visuospatial/constructional (figure copy and line orientation); 3-Language (picture naming and semantic fluency); 4-Attention (digit span and coding); 5-Delayed memory (list recall, list recognition, story memory, and figure recall) will be reported.
Time frame: Baseline, Week 88
Change From Baseline in Clinical Dementia Rating- Sum of Boxes (CDR-SB) at Week 104
CDR is a global clinical staging instrument that includes 3 cognitive and 3 functional ratings, including: memory, orientation, judgment and problem solving, involvement in community affairs, home and hobbies, and personal care based on the CDR interview. The CDR is scored 2 ways yielding a global CDR score (CDR GS, derived from an algorithm including categorical scoring of 0, 0.5, 1, 2, and 3), as well as CDR-Sum of Boxes (CDR-SB, the continuous sum of 6 domains, up to a total score of 18, with higher scores representing worse disease state). The Sum of boxes and global score is calculated from the overall CDR.
Time frame: Baseline, Week 104
Change from Baseline in Neuropsychiatric Inventory (NPI) at Week 104
The NPI is a measure of psychobehavioral disturbances, assessing the frequency and severity of disturbances in 12 domains. Frequency for each domain is rated on a 4 point scale (from 1=rarely to 4=very often) and severity on a 3 point scale (from 1=mild to 3=severe), with the score for each domain being the product of the frequency and severity scores, such that each domain is scored from 1 to 12. The NPI total score is the sum of the 12 domain scores, ranging from 0 (best) to 144 (worst).
Time frame: Baseline, Week 104
Percentage of Participants Progressing From Clinical Dementia Rating- Global Score (CDR-GS) 0 to 0.5 or Higher, 0.5 to 1 or Higher, 1 to 2 or Higher, from Baseline to Post-baseline through Week 104
The CDR is a subjectively rated outcome measure that serves as a global clinical staging instrument that includes 3 cognitive and 3 functional ratings, including: 1) memory, 2) orientation, 3) judgment and problem solving, 4) involvement in community affairs, 5) home and hobbies, and 6) personal care based on the CDR interview. The CDR is scored 2 ways yielding a global CDR score (CDR GS, derived from an algorithm developed by the Knight Alzheimer Disease Research Center at Washington University School of Medicine in St. Louis, Missouri, US, and including categorical scoring of 0= cognitively unimpaired, 0.5= mild cognitive impairment, 1= mild dementia, 2= moderate dementia, and 3= severe dementia), as well as CDR-Sum of Boxes (CDR-SB, the continuous sum of 6 domains, up to a total score of 18, with higher scores representing worse disease state).
Time frame: From Baseline through Week 104
Change From Baseline in Brain tau Burden as Measured by tau PET at Week 104
Change from baseline in brain tau burden, as measured by tau positron emission tomography (PET) will be assessed.
Time frame: Baseline, Week 104
Change From Baseline in Cerebrospinal Fluid (CSF) concentrations of Total, Free, and Bound p217+tau Fragments at Week 104
Change from baseline in CSF concentrations of total, free, and bound p217+tau (phosphorylated tau) fragments will be assessed.
Time frame: Baseline, Week 104
CSF Concentrations of JNJ-63733657
CSF concentrations of JNJ-63733657 will be assessed.
Time frame: At Weeks 52, 104, 208 (End of Treatment)
Serum Concentrations of JNJ-63733657
Serum concentrations of JNJ-63733657 will be assessed.
Time frame: At Weeks 4, 8, 12, 16, 20, 24, 36, 52, 76, 104, 128, 156, 180, 208, 232 (End of treatment)
Anti-Drug Antibody to JNJ-63733657
Anti-drug antibody to JNJ-63733657 will be assessed.
Time frame: Up to 245 Weeks (90 days [+-7 days] after last dose of study intervention)
Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to that medicinal product.
Time frame: Up to 245 Weeks
Number of Participants with Treatment-Emergent Adverse Event of Special Interest (AESI)
Number of participants with a treatment-emergent AESI will be reported.
Time frame: Up to 245 Weeks
Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability
An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.
Time frame: Up to 245 Weeks
Number of Participants with Electrocardiogram (ECG) Abnormalities
Number of participants with ECG abnormalities will be reported.
Time frame: Up to 245 Weeks
Number of Participants with Clinical Laboratory Abnormalities
Number of participants with clinical laboratory (hematology, clinical chemistry, and urinalysis) abnormalities will be assessed.
Time frame: Up to 245 Weeks
Number of Participants with Physical and Neurological Examination Abnormalities
Number of participants with physical (body weight, height) and neurological (evaluation of mental status, cranial nerves, motor ability \[including strength, tone, and involuntary movements\], coordination \[including finger-to-nose, gait, and postural reflexes\], and sensation \[including proprioception, cold, light touch, and deep tendon reflexes\]) examination abnormalities will be reported.
Time frame: Up to 245 Weeks
Percentage of Participants with Vital Sign Abnormalities
Percentage of participants with vital sign abnormalities (temperature, pulse rate, systolic blood pressure \[BP\], diastolic BP) will be reported.
Time frame: Up to 245 Weeks
Changes From Baseline in Brain Magnetic Resonance Imaging (MRI) Safety Findings
Changes from baseline in brain MRI safety findings (brain tumors, aneurysm or atrioventricular malformations, territorial stroke (excluding smaller watershed strokes), recent hemorrhage (parenchymal or subdural), or obstructive hydrocephalus) will be assessed.
Time frame: Baseline and Up to 4.5 years (End of treatment)
Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) score
C-SSRS is semi structured clinician-administered questionnaire designed to solicit the occurrence, severity, and frequency of suicide-related ideation and behaviors . Total score ranges from 1 to 10, a score of 0 will be assigned (0="no event that can be assessed on the basis of C-SSRS"). Higher scores indicate greater severity. The maximum score assigned for each participant will also be summarized into one of three broad categories: no suicidal ideation or behavior (0), suicidal ideation (1 to 5), suicidal behavior (6 to 10).
Time frame: Baseline and Up to 245 Weeks
Showing the first 100 of 122 sites across 10 countries.
Plan to share: Yes — The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
This study is terminated, as verified in Mar 2026. You cannot join it, but the record below documents what was studied.
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