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

NCT03375697 | Completed Phase 1

• 3 other identifiers: CR10839263733657EDI10012017-003852-21
• Study Type: interventional
• Target: 72
• Locations: 4 countries
• Sites: 7

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).

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (12)

• 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): 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)

• MAD (Part 2): Area Under the Serum JNJ-63733657 Concentration-time Curve During a Dosing Interval (t) (AUC tau)

  Up to Day 85 (MAD)

Study Arms (2)

SAD (Part 1): Healthy Subjects

EXPERIMENTAL

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.

Drug: JNJ-63733657; Drug: Placebo

MAD (Part 2): Subjects With Alzheimer's Disease (AD)

EXPERIMENTAL

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.

Drug: JNJ-63733657; Drug: Placebo

Interventions

JNJ-63733657 DRUG

Subjects will receive single (Part 1) or multiple (Part 2) ascending dose levels of JNJ-63733657 intravenously.

MAD (Part 2): Subjects With Alzheimer's Disease (AD); SAD (Part 1): Healthy Subjects

Placebo DRUG

Subjects will receive matching placebo intravenously.

MAD (Part 2): Subjects With Alzheimer's Disease (AD); SAD (Part 1): Healthy Subjects

Eligibility Criteria

• Age: 55 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)
• \- 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)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (7)

Clinical Pharmacology Unit

Merksem, 2170, Belgium

Location

Klinik für Neurodegenerative Erkrankungen und Gerontopsychiatrie

Bonn, 53127, Germany

Location

CTC North GmbH & Co. KG

Hamburg, 20251, Germany

Location

Universitätsklinikum des Saarlandes

Homburg / Saar, 66421, Germany

Location

Centre for Human Drug Research

Leiden, 2333 CL, Netherlands

Location

Hosp. Clinico San Carlos

Madrid, 28040, Spain

Location

Hosp. Univ. I Politecni La Fe

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2017
• First Posted: December 18, 2017
• Study Start: December 22, 2017
• Primary Completion: December 16, 2019
• Study Completion: December 16, 2019
• Last Updated: April 27, 2025

Record last verified: 2025-04

Locations

BE (1); DE (3); ES (2); NL (1)