A Study to Investigate Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-63733657 in Healthy Subjects and Subjects With Alzheimer's Disease

Alzheimer Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03375697
• Other study ID #: CR108392
• Secondary ID: 63733657EDI10012
• Status: Completed
• Phase: Phase 1
• Start date: December 22, 2017
• Est. completion date: December 16, 2019

Study information

• Verified date: December 2022
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: December 16, 2019
• Est. primary completion date: December 16, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 55 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• JNJ-63733657
Subjects will receive single (Part 1) or multiple (Part 2) ascending dose levels of JNJ-63733657 intravenously.
• Placebo
Subjects will receive matching placebo intravenously.

Locations

Country	Name	City	State
Belgium	Clinical Pharmacology Unit	Merksem
Germany	Klinik für Neurodegenerative Erkrankungen und Gerontopsychiatrie	Bonn
Germany	CTC North GmbH & Co. KG	Hamburg
Germany	Universitätsklinikum des Saarlandes	Homburg / Saar
Netherlands	Centre for Human Drug Research	Leiden
Spain	Hosp. Clinico San Carlos	Madrid
Spain	Hosp. Univ. I Politecni La Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

Belgium,  Germany,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to Day 106
Primary	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.	Up to Day 162
Secondary	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.	Up to Day 106 (SAD) and up to Day 162 (MAD)
Secondary	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.	Up to Day 106 (SAD) and up to Day 162 (MAD)
Secondary	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.	Up to Day 106 (SAD) and up to Day 162 (MAD)
Secondary	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.	Up to Day 106 (SAD) and up to Day 162 (MAD)
Secondary	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).	Up to Day 85 (MAD)
Secondary	MAD (Part 2): Accumulation Ratio (R)	R is obtained by dividing AUC of JNJ-63733657 at two different time points.	Up to Day 162 (MAD)
Secondary	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]).	Up to Day 106 (SAD) and up to Day 162 (MAD)
Secondary	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.	Up to Day 106 (SAD) and up to Day 162 (MAD)
Secondary	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).	Up to Day 106 (SAD) and up to Day 162 (MAD)
Secondary	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.	Up to Day 57 (SAD) and up to Day 148 (MAD)
Secondary	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.	Up to Day 106 (SAD) and up to Day 162 (MAD)
Secondary	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.	Up to Day 106 (SAD) and up to Day 162 (MAD)