A study of JNJ-64042056 in participants with preclinical Alzheimer's disease

INTERVENTION: Participants will be assigned by chance to one of two treatment groups: JNJ‐64042056 or placebo. Participants will be assigned randomly by a central randomisation process. Participants will receive the study drug/treatment on Day 1, at 2 months, at 6 months and then 6 additional injections occurring every 6 months up to Week 180 (a total of 9 injections throughout the study period). The study intervention will be administered at the study site via an intramuscular injection in the deltoid muscle (upper arm). After the end of the study at Week 206, participants will have an option to participate in a separate open‐label extension study (if eligible). CONDITION: Preclinical Alzheimer’s Disease ; Nervous System Diseases PRIMARY OUTCOME: Change From Baseline in Preclinical Alzheimer's Disease Cognitive Composite 5 (PACC‐5) Total Scores up to Week 206 SECONDARY OUTCOME: Baseline up to Week 206 (unless noted otherwise):; 1. Change From Baseline in Brain tau Burden as Measured by tau PET‐ Baseline and Weeks 102, 154 and 206; 2. Change From Baseline in PACC‐5 Individual Domain Scores; 3. Time to Event of Clinical Progression as Measured by Clinical Dementia Rating‐Global Score (CDR‐GS); 4. Change From Baseline in Clinical Dementia Rating‐Sum of Boxes (CDR‐SB) Scores; 5. Change from Baseline in Tau PET Standardized Uptake Value Ratio (SUVR) Biomarkers (tau Naiive Composite ROI and Other ROIs); 6. Change From Baseline in p217+tau; 7. Change From Baseline in PACC‐5 Total Score ‐ Baseline up to Week 180; 8. Change From Baseline in Brain Tau Burden as Measured by Tau PET in Other ROI; 9. Change From Baseline in Alzheimer's Disease Cooperative Study ‐ Activities of Daily Living ‐Prevention Instrument (ADCS‐ADL‐PI); 10. Change From Baseline in Mild Behavioral Impairment Checklist (MBI‐C) Score; 11. Change From Baseline in the Quality of Life‐ Alzheimer's Disease (QoL‐AD); 12. Change From Baseline in European Quality of Life‐5 Dimensions 5‐Levels (EQ‐5D‐5L) Score; 13. Change From Baseline in Resource Utilization in Dementia‐Lite (RUD‐Lite) Score; 14. Levels of IgG Titers Against Enriched Paired Helical Filaments (ePHF), p‐tau and tau in Serum; 15. Number of Participants With Treatment‐Emergent Adverse Events (TEAEs) ‐ Up to Week 208; 16. Number of Participants With Reactogenicity ‐ Up to Week 182; 17. Change from Baseline in Vital Signs; 18. Change From Baseline in Clinical Laboratory Values; 19. Change from Baseline in Electrocardiogram (ECG) Values; 20. Change From Baseline in Columbia‐Suicidality Severity Rating Scale (C‐SSRS); 21. Change From Baseline in Magnetic Resonance Imaging (MRI) Findings; INCLUSION CRITERIA: 1. 55 to 75 years of age, inclusive, at randomisation visit. 2. Elevated brain tau pathology defined as Braak 3 ROI SUVR > 1.1 on a screening tau PET scan, reviewed centrally by a qualified reader. 3. CDR global score of 0 at screening and baseline. 4. MMSE =27 (with educational adjustment). 5. Able to read and write and with a minimum 5 years of formal education as reported by participant and study partner at screening.