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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Alzheimer Disease

Treatments: Drug: Placebo; Drug: JNJ-63733657

Study type: Interventional

Funder types: Industry

Identifiers

NCT03375697

CR108392

2017-003852-21 (EudraCT Number)

63733657EDI1001 (Other Identifier)

Details and patient eligibility

About

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).

Enrollment: 72 patients

Sex: All

Ages: 55 to 75 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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72 participants in 2 patient groups

SAD (Part 1): Healthy Subjects

Experimental group

Description:

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.

Treatment:

Drug: JNJ-63733657

Drug: Placebo

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

Experimental group

Description:

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.

Treatment:

Drug: JNJ-63733657

Drug: Placebo