Clinical trial NCT03375697: A Study to Investigate Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-63733657 in Healthy Subjects and Subjects With Alzheimer's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer Disease
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2017-12-18
Enrollment: 72
Sex: ALL
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


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)

Primary outcomes:
measure: Single Ascending Dose (SAD) (Part 1): Number of Subjects With Adverse Events as a Measure of Safety and Tolerability of JNJ-63733657
timeFrame: Up to Day 106
measure: Multiple Ascending Dose (MAD) (Part 2): Number of Subjects With Adverse Events as a Measure of Safety and Tolerability of JNJ-63733657
timeFrame: Up to Day 162
Secondary outcomes:
measure: SAD (Part 1) and MAD (Part 2): Maximum Observed Serum Concentration (Cmax) of JNJ-63733657
timeFrame: Up to Day 106 (SAD) and up to Day 162 (MAD)
measure: SAD (Part 1) and MAD (Part 2): Time to Reach Maximum Observed Serum Concentration (Tmax) of JNJ-63733657
timeFrame: Up to Day 106 (SAD) and up to Day 162 (MAD)
measure: 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
timeFrame: Up to Day 106 (SAD) and up to Day 162 (MAD)
measure: 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
timeFrame: Up to Day 106 (SAD) and up to Day 162 (MAD)
measure: MAD (Part 2): Area Under the Serum JNJ-63733657 Concentration-time Curve During a Dosing Interval (t) (AUC tau)
timeFrame: Up to Day 85 (MAD)
measure: MAD (Part 2): Accumulation Ratio (R)
timeFrame: Up to Day 162 (MAD)
measure: SAD (Part 1) and MAD (Part 2): Total Systemic Clearance (CL) of JNJ-63733657
timeFrame: Up to Day 106 (SAD) and up to Day 162 (MAD)
measure: SAD (Part 1) and MAD (Part 2): Volume of Distribution at Steady-State (Vss) of JNJ-63733657
timeFrame: Up to Day 106 (SAD) and up to Day 162 (MAD)
measure: SAD (Part 1) and MAD (Part 2): Terminal Half-Life(t[1/2]) of JNJ-63733657
timeFrame: Up to Day 106 (SAD) and up to Day 162 (MAD)
measure: SAD (Part 1) and MAD (Part 2): JNJ-63733657 Concentration in Cerebrospinal Fluid (CSF)
timeFrame: Up to Day 57 (SAD) and up to Day 148 (MAD)
measure: SAD (Part 1) and MAD (Part 2): Number of Subjects With Anti-JNJ-6373365 Antibodies as a Measure of Immunogenicity
timeFrame: Up to Day 106 (SAD) and up to Day 162 (MAD)
measure: SAD (Part 1) and MAD (Part 2): Percent Change From Baseline in Total, Free, and Bound tau Biomarker Fragments in CSF
timeFrame: Up to Day 106 (SAD) and up to Day 162 (MAD)
Other outcomes:
Locations:
city: Merksem
country: Belgium
facility: Clinical Pharmacology Unit
city: Bonn
country: Germany
facility: Klinik für Neurodegenerative Erkrankungen und Gerontopsychiatrie
city: Hamburg
country: Germany
facility: CTC North GmbH & Co. KG
city: Homburg / Saar
country: Germany
facility: Universitätsklinikum des Saarlandes
city: Leiden
country: Netherlands
facility: Centre for Human Drug Research
city: Madrid
country: Spain
facility: Hosp. Clinico San Carlos
city: Valencia
country: Spain
facility: Hosp. Univ. I Politecni La Fe
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: