A 2-Part Randomized, Placebo-Controlled, Double-Blind, Single and Multiple Ascending Dose Study to Investigate Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-63733657 in Healthy Subjects and Subjects With Alzheimer's Disease
Overview
- Phase
- Phase 1
- Intervention
- JNJ-63733657
- Conditions
- Alzheimer Disease
- Sponsor
- Janssen Research & Development, LLC
- Enrollment
- 72
- Locations
- 7
- Primary Endpoint
- Single Ascending Dose (SAD) (Part 1): Number of Subjects With Adverse Events as a Measure of Safety and Tolerability of JNJ-63733657
- Status
- Completed
- Last Updated
- last year
Overview
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).
Investigators
Eligibility Criteria
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 Exclusion Criteria
- •Any potential subject who meets any of the following criteria will be excluded from participating in the study:
- •History of or current liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic (including but not limited to neurodegenerative disease (excluding AD for Part 2) \[example, Parkinson's disease\], seizure disorders, transient ischemic attacks, etc.), hematologic (including coagulation disorders), rheumatologic, psychiatric, or metabolic disturbances, any inflammatory illness or any other illness that the Investigator considers should exclude the subject
- •Relevant history of or current neurological disease (other than prodromal AD or mild AD for Part 2), which in the opinion of the investigator may make interpretation of possible new neurological signs or symptoms difficult
- •History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening (per screening evaluations)
- •History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-Hepatitis C virus \[HCV\]) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at screening (per screening evaluations)
- •Specific Exclusion Criteria Part 1 - Mini-Mental State Examination (MMSE) score less than or equal to (\<=) 27 at screening
- •Specific Exclusion Criteria Part 2
- •Evidence of brain disease, other than AD, that could explain the cognitive deficit (including, but not limited to, vascular encephalopathy or strokes, as imaged by cerebral Magnetic resonance imaging (MRI)
Arms & Interventions
SAD (Part 1): Healthy Subjects
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.
Intervention: JNJ-63733657
SAD (Part 1): Healthy Subjects
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.
Intervention: Placebo
MAD (Part 2): Subjects With Alzheimer's Disease (AD)
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.
Intervention: JNJ-63733657
MAD (Part 2): Subjects With Alzheimer's Disease (AD)
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.
Intervention: Placebo
Outcomes
Primary Outcomes
Single Ascending Dose (SAD) (Part 1): Number of Subjects With Adverse Events as a Measure of Safety and Tolerability of JNJ-63733657
Time Frame: 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
Time Frame: 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 Outcomes
- 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))
- MAD (Part 2): Area Under the Serum JNJ-63733657 Concentration-time Curve During a Dosing Interval (t) (AUC tau)(Up to Day 85 (MAD))
- MAD (Part 2): Accumulation Ratio (R)(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(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)(Up to Day 57 (SAD) and up to Day 148 (MAD))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))