Alzheimer Disease
Conditions
Brief summary
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).
Interventions
DRUGJNJ-63733657
Subjects will receive single (Part 1) or multiple (Part 2) ascending dose levels of JNJ-63733657 intravenously.
DRUGPlacebo
Subjects will receive matching placebo intravenously.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
General Inclusion Criteria: * Body mass index (BMI) between 18 and 35 kilogram per meter square (kg/m\^2), inclusive (BMI = weight/height\^2) and body weight greater than 40 kilogram (kg) but less than 110 kg at screening * Women must not be of childbearing potential 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: * Clinical Dementia Rating Scale (CDR) global rating score of 0.5 or 1.0 at screening * Must have a reliable informant (example, relative, partner, friend) * Must have cerebrospinal fluid (CSF) finding consistent with Alzheimer's disease (AD) pathology
Exclusion criteria
General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Single Ascending Dose (SAD) (Part 1): Number of Subjects With Adverse Events as a Measure of Safety and Tolerability of JNJ-63733657 | Up to Day 106 | 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. |
| Multiple Ascending Dose (MAD) (Part 2): Number of Subjects With Adverse Events as a Measure of Safety and Tolerability of JNJ-63733657 | Up to Day 162 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Up to Day 106 (SAD) and up to Day 162 (MAD) | 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. |
| 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 | Up to Day 106 (SAD) and up to Day 162 (MAD) | AUC (0-infinity) is defined as area under the serum JNJ-63733657 concentration-time curve from time 0 to infinite time. |
| MAD (Part 2): Area Under the Serum JNJ-63733657 Concentration-time Curve During a Dosing Interval (t) (AUC tau) | Up to Day 85 (MAD) | AUC tau is defined as area under the serum JNJ-63733657 concentration-time curve during a dosing interval (tau). |
| MAD (Part 2): Accumulation Ratio (R) | Up to Day 162 (MAD) | R is obtained by dividing AUC of JNJ-63733657 at two different time points. |
| SAD (Part 1) and MAD (Part 2): Total Systemic Clearance (CL) of JNJ-63733657 | Up to Day 106 (SAD) and up to Day 162 (MAD) | 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\[0-infinity\]). |
| SAD (Part 1) and MAD (Part 2): Maximum Observed Serum Concentration (Cmax) of JNJ-63733657 | Up to Day 106 (SAD) and up to Day 162 (MAD) | The Cmax is the maximum observed serum concentration of drug JNJ-63733657. |
| SAD (Part 1) and MAD (Part 2): Terminal Half-Life(t[1/2]) of JNJ-63733657 | Up to Day 106 (SAD) and up to Day 162 (MAD) | 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). |
| SAD (Part 1) and MAD (Part 2): JNJ-63733657 Concentration in Cerebrospinal Fluid (CSF) | Up to Day 57 (SAD) and up to Day 148 (MAD) | CSF concentration assessment will be done to characterize the pharmacokinetics (PK) to estimate CSF concentration of JNJ-63733657. |
| SAD (Part 1) and MAD (Part 2): Number of Subjects With Anti-JNJ-6373365 Antibodies as a Measure of Immunogenicity | Up to Day 106 (SAD) and up to Day 162 (MAD) | Number of subjects with Anti-JNJ-63733657 antibodies will be evaluated in serum samples and potential CSF samples. |
| SAD (Part 1) and MAD (Part 2): Percent Change From Baseline in Total, Free, and Bound tau Biomarker Fragments in CSF | Up to Day 106 (SAD) and up to Day 162 (MAD) | 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. |
| SAD (Part 1) and MAD (Part 2): Volume of Distribution at Steady-State (Vss) of JNJ-63733657 | Up to Day 106 (SAD) and up to Day 162 (MAD) | 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. |
| SAD (Part 1) and MAD (Part 2): Time to Reach Maximum Observed Serum Concentration (Tmax) of JNJ-63733657 | Up to Day 106 (SAD) and up to Day 162 (MAD) | Tmax is defined as time to reach the maximum observed serum JNJ-63733657 concentration. |
Countries
Belgium, Germany, Netherlands, Spain
Outcome results
None listed