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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
72
Subjects will receive single (Part 1) or multiple (Part 2) ascending dose levels of JNJ-63733657 intravenously.
Subjects will receive matching placebo intravenously.
Clinical Pharmacology Unit
Merksem, Belgium
Klinik für Neurodegenerative Erkrankungen und Gerontopsychiatrie
Bonn, Germany
CTC North GmbH & Co. KG
Hamburg, Germany
Universitätsklinikum des Saarlandes
Homburg / Saar, Germany
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)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Centre for Human Drug Research
Leiden, Netherlands
Hosp. Clinico San Carlos
Madrid, Spain
Hosp. Univ. I Politecni La Fe
Valencia, Spain
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)