A Phase 1 interventional study of JNJ-63733657 and Placebo in Alzheimer Disease, sponsored by Janssen Research & Development, LLC. Completed at 7 sites in 4 countries. Open to participants aged 55 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-04-27.
Sponsored by Janssen Research & Development, LLC · Phase 1, Interventional, and Treatment
The purpose of this study is to assess the safety and tolerability of JNJ-63733657 following single ascending intravenous (IV) dose administration in healthy subjects (Part 1) and multiple ascending IV dose administrations in subjects with prodromal or mild Alzheimer's disease (AD) (Part 2).
General Inclusion Criteria:
Specific Inclusion Criteria Part 2:
Each potential subject enrolled in Part 2 must satisfy all of the following specific criteria in addition to the general criteria to be enrolled in the study:
Exclusion Criteria:
General Exclusion Criteria
Any potential subject who meets any of the following criteria will be excluded from participating in the study:
Specific Exclusion Criteria Part 1 - Mini-Mental State Examination (MMSE) score less than or equal to (\<=) 27 at screening
Specific Exclusion Criteria Part 2
In Part 1, single ascending intravenous (IV) doses of JNJ-63733657 or placebo will be administered to sequential cohorts (Cohorts 1 to 5) of healthy subjects on Day 1. The progression to the next (higher) dose level is dependent on acceptable safety and tolerability profile of JNJ-63733657 obtained after dose administration of the current dose level. Here, SAD indicates single ascending dose.
Drug: JNJ-63733657 · Drug: Placebo
In Part 2, multiple ascending IV doses of JNJ-63733657 or placebo will be evaluated at three dose levels in sequential cohorts in subjects with prodromal or mild AD; 3 doses will be administered over a period of 8 weeks (Day 1, Day 29, Day 57). The starting dose will be decided based on the data from Part 1. Escalations will be done based on safety and tolerability similar to Part 1. Doses will not exceed those tested in Part 1. Here, MAD indicates multiple ascending dose.
Drug: JNJ-63733657 · Drug: Placebo
Subjects will receive single (Part 1) or multiple (Part 2) ascending dose levels of JNJ-63733657 intravenously.
Subjects will receive matching placebo intravenously.
Single Ascending Dose (SAD) (Part 1): Number of Subjects With Adverse Events as a Measure of Safety and Tolerability of JNJ-63733657
An adverse event is any untoward medical event that occurs in a subject administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Time frame: Up to Day 106
Multiple Ascending Dose (MAD) (Part 2): Number of Subjects With Adverse Events as a Measure of Safety and Tolerability of JNJ-63733657
An adverse event is any untoward medical event that occurs in a subject administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Time frame: Up to Day 162
SAD (Part 1) and MAD (Part 2): Maximum Observed Serum Concentration (Cmax) of JNJ-63733657
The Cmax is the maximum observed serum concentration of drug JNJ-63733657.
Time frame: Up to Day 106 (SAD) and up to Day 162 (MAD)
SAD (Part 1) and MAD (Part 2): Time to Reach Maximum Observed Serum Concentration (Tmax) of JNJ-63733657
Tmax is defined as time to reach the maximum observed serum JNJ-63733657 concentration.
Time frame: Up to Day 106 (SAD) and up to Day 162 (MAD)
SAD (Part 1) and MAD (Part 2): Area Under the Serum Concentration-time Curve From Time Zero to Time of the Last Observed Quantifiable Concentration (AUC [0-Last]) of JNJ-63733657
AUC (0-last) is defined as area under the serum JNJ-63733657 concentration-time curve from time 0 to time of the last observed quantifiable concentration.
Time frame: Up to Day 106 (SAD) and up to Day 162 (MAD)
SAD (Part 1) and MAD (Part 2): Area Under the Serum Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-63733657
AUC (0-infinity) is defined as area under the serum JNJ-63733657 concentration-time curve from time 0 to infinite time.
Time frame: Up to Day 106 (SAD) and up to Day 162 (MAD)
MAD (Part 2): Area Under the Serum JNJ-63733657 Concentration-time Curve During a Dosing Interval (t) (AUC tau)
AUC tau is defined as area under the serum JNJ-63733657 concentration-time curve during a dosing interval (tau).
Time frame: Up to Day 85 (MAD)
MAD (Part 2): Accumulation Ratio (R)
R is obtained by dividing AUC of JNJ-63733657 at two different time points.
Time frame: Up to Day 162 (MAD)
SAD (Part 1) and MAD (Part 2): Total Systemic Clearance (CL) of JNJ-63733657
CL is a quantitative measure of the rate at which JNJ-63733657 is removed from the body. The total systemic clearance after intravenous dose is estimated by dividing the total administered dose by the plasma Area Under the Serum Concentration-Time Curve From Time Zero to Infinite Time (AUC\[0-infinity\]).
Time frame: Up to Day 106 (SAD) and up to Day 162 (MAD)
SAD (Part 1) and MAD (Part 2): Volume of Distribution at Steady-State (Vss) of JNJ-63733657
Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state Vss is the apparent volume of distribution at steady-state which is estimated by (D/AUC\[0-infinity\])\*(AUMC\[0-infinity\])/AUC\[0-infinity\]) where D is the dose of study drug, AUMC(0-infinity) is the area under the first moment curve extrapolated to infinity and AUC(0-infinity) is the area under the serum concentration-time curve from time zero to infinite time.
Time frame: Up to Day 106 (SAD) and up to Day 162 (MAD)
SAD (Part 1) and MAD (Part 2): Terminal Half-Life(t[1/2]) of JNJ-63733657
t(1/2) is associated with the terminal slope (lambda \[z\]) of the semi-logarithmic drug concentration-time curve, calculated as 0.693/lambda(z).
Time frame: Up to Day 106 (SAD) and up to Day 162 (MAD)
SAD (Part 1) and MAD (Part 2): JNJ-63733657 Concentration in Cerebrospinal Fluid (CSF)
CSF concentration assessment will be done to characterize the pharmacokinetics (PK) to estimate CSF concentration of JNJ-63733657.
Time frame: Up to Day 57 (SAD) and up to Day 148 (MAD)
SAD (Part 1) and MAD (Part 2): Number of Subjects With Anti-JNJ-6373365 Antibodies as a Measure of Immunogenicity
Number of subjects with Anti-JNJ-63733657 antibodies will be evaluated in serum samples and potential CSF samples.
Time frame: Up to Day 106 (SAD) and up to Day 162 (MAD)
SAD (Part 1) and MAD (Part 2): Percent Change From Baseline in Total, Free, and Bound tau Biomarker Fragments in CSF
Percent change from baseline in total, free, and bound tau (phosphorylation site) biomarker fragments in CSF will be evaluated to assess the effect of JNJ-63733657.
Time frame: Up to Day 106 (SAD) and up to Day 162 (MAD)
This study is completed, as verified in Apr 2025. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Janssen Research & Development, LLC