A Study in Healthy Participants to Evaluate the Effect of JNJ-54175446 on Amyloid Biomarkers and Cytokine Profiles in Cerebrospinal Fluid and Plasma

An Exploratory, Single-Blind, Placebo-Controlled, Randomized, Single- and Multiple-Dose Pharmacodynamics Study in Healthy Subjects to Evaluate the Effect of JNJ-54175446 on Amyloid Biomarkers and Cytokine Profiles in Cerebrospinal Fluid and Plasma

The primary purpose of this study is to investigate the effects of JNJ-54175446 (dose response) on levels of Aβ fragments (Aβ1-42, Aβ1-40, Aβ1-38, Aβ1-37) in plasma and cerebrospinal fluid (CSF), the effects of JNJ-54175446 on markers of (neuro) inflammation/protection in blood and CSF and the pharmacokinetics of JNJ-54175446 followed by single and multiple dose administration.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: JNJ-54175446; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Merksem, Belgium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participants must have a body mass index (BMI) between 18 and 32 kilogram (kg)/ meter (m)^2, inclusive (BMI = weight/height^2)
• Participant must be healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG)

Part 1 and 2 (Elderly Participants):

• Healthy male or female participants between 55 and 75 years of age, inclusive
• Participant must be healthy on the basis of both physical and neurological examination performed at Screening and at admission to the clinical unit

Part 1 (Young Participants):

- Healthy male participants between 18 and 45 years of age, inclusive

Exclusion Criteria:

• Participant has a history of or current liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances, any inflammatory illness or any other illness that the Investigator considers should exclude the participant
• Participant has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening (per Screening evaluations)
• Participant has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening (per Screening evaluations)
• Participant has a history of malignancy within 5 years before Screening
• Participant has signs of increased intracranial pressure based on fundoscopy at Screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Cohort A1 (JNJ-54175446 30 milligram[mg]); Healthy elderly participants will receive single dose of 30mg JNJ-54175446.	Drug: JNJ-54175446; Participants will receive a single oral dose of JNJ-54175446 suspension orally once on Day 1 of part 1 and Day 1 to Day 7 in part 2.
Experimental: Part 1: Cohort A1 (JNJ-54175446 100mg); Healthy elderly participants will receive single dose of 100mg JNJ-54175446.	Drug: JNJ-54175446; Participants will receive a single oral dose of JNJ-54175446 suspension orally once on Day 1 of part 1 and Day 1 to Day 7 in part 2.
Experimental: Part 1: Cohort A1 (JNJ-54175446 300mg); Healthy elderly participants will receive single dose of 300mg JNJ-54175446.	Drug: JNJ-54175446; Participants will receive a single oral dose of JNJ-54175446 suspension orally once on Day 1 of part 1 and Day 1 to Day 7 in part 2.
Experimental: Part 1: Cohort A1 (Placebo); Healthy elderly participants will receive single dose of placebo.	Drug: Placebo; Participants will receive a single oral dose of JNJ-54175446 suspension orally once on Day 1 of part 1 and Day 1 to Day 7 in part 2.
Experimental: Part 1: Cohort A2 (JNJ-54175446 D1 mg); Healthy elderly participants will receive an additional dose D1 mg [less than or equal to (<=) 600 mg] of JNJ-54175446, to be determined.	Drug: JNJ-54175446; Participants will receive a single oral dose of JNJ-54175446 suspension orally once on Day 1 of part 1 and Day 1 to Day 7 in part 2.
Experimental: Part 1: Cohort A3 (JNJ-54175446 D2 mg); Healthy young participants will receive a single dose D2 mg (<= 600 mg) of JNJ-54175446, to be determined.	Drug: JNJ-54175446; Participants will receive a single oral dose of JNJ-54175446 suspension orally once on Day 1 of part 1 and Day 1 to Day 7 in part 2.
Experimental: Part 1: Cohort A3 (Placebo); Healthy young participants will receive a single dose of placebo.	Drug: Placebo; Participants will receive a single oral dose of JNJ-54175446 suspension orally once on Day 1 of part 1 and Day 1 to Day 7 in part 2.
Experimental: Part 2: Cohort B1 (JNJ-54175446 D3 mg); Healthy elderly participants will receive multiple dose levels D3 mg (<= 450 mg) of JNJ-54175446 determined based on the results from Cohort A1.	Drug: JNJ-54175446; Participants will receive a single oral dose of JNJ-54175446 suspension orally once on Day 1 of part 1 and Day 1 to Day 7 in part 2.
Experimental: Part 2: Cohort B1 (Placebo); Healthy elderly participants will receive placebo determined based on the results from Cohort A1.	Drug: Placebo; Participants will receive a single oral dose of JNJ-54175446 suspension orally once on Day 1 of part 1 and Day 1 to Day 7 in part 2.
Experimental: Part 2: Cohort B2 (JNJ-54175446 D4 mg); Healthy elderly participants will receive multiple dose levels D4 mg (<= 450 mg) of JNJ-54175446 determined based on the results from Cohort A1.	Drug: JNJ-54175446; Participants will receive a single oral dose of JNJ-54175446 suspension orally once on Day 1 of part 1 and Day 1 to Day 7 in part 2.
Experimental: Part 2: Cohort B2 (Placebo); Healthy elderly participants will receive placebo determined based on the results from Cohort A1	Drug: Placebo; Participants will receive a single oral dose of JNJ-54175446 suspension orally once on Day 1 of part 1 and Day 1 to Day 7 in part 2.
Experimental: Part 2: Cohort B3 (JNJ-54175446 D5 mg); Healthy elderly participants will receive multiple dose levels D5 mg (<= 450 mg) of JNJ-54175446 determined based on the results from Cohort A1.	Drug: JNJ-54175446; Participants will receive a single oral dose of JNJ-54175446 suspension orally once on Day 1 of part 1 and Day 1 to Day 7 in part 2.
Experimental: Part 2: Cohort B3 (Placebo); Healthy elderly participants will receive placebo determined based on the results from Cohort A1	Drug: Placebo; Participants will receive a single oral dose of JNJ-54175446 suspension orally once on Day 1 of part 1 and Day 1 to Day 7 in part 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Effects of JNJ-54175446 (Dose Response) on Levels of Aβ Fragments in Plasma	Part 1: Up to Day 2
The Effects of JNJ-54175446 (Dose Response) on Levels of Aβ Fragments in Plasma	Part 2: Up to Day 8
The Effects of JNJ-54175446 (Dose Response) on Levels of Aβ Fragments in Cerebrospinal Fluid (CSF)	Part 1: Up to Day 2
The Effects of JNJ-54175446 (Dose Response) on Levels of Aβ Fragments in Cerebrospinal Fluid (CSF)	Part 2: Up to Day 8
The Effects of JNJ-54175446 (Dose Response) on Markers of (Neuro)Inflammation / Protection in Blood	Part 1: Up to Day 2
The Effects of JNJ-54175446 (Dose Response) on Markers of (Neuro)Inflammation / Protection in Blood	Part 2: Up to Day 8
The Effects of JNJ-54175446 (Dose Response) on Markers of (Neuro)Inflammation / Protection in CSF	Part 1: Up to Day 2
The Effects of JNJ-54175446 (Dose Response) on Markers of (Neuro)Inflammation / Protection in CSF	Part 2: Up to Day 8
Maximum Observed Plasma Concentration (Cmax) After Single- and Multiple-Dose Administration	Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8
Minimum Observed Plasma Concentration (Cmin)During Dosing Interval	Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8
The Observed Plasma Concentration Just Prior to the Beginning or at the end of a Dosing Interval of any Dose Other Than the First Dose (Ctrough)	Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8
Average Plasma Concentration at Steady State Over the Dosing Interval (Cavg)	Part 1: Day 1 - Day 2; Par 2: Day 1, Day 2 to 6, Day 7, Day 8
Time to Reach the Maximum Plasma Concentration, After Single- and Multiple-Dose Administration (Tmax)	Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8
Area Under The Concentration-Time Curve From 0 To t Hours Postdosing (AUCt)	Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8
Area Under the Concentration-Time Curve From 0 to 24 Hours Postdosing (AUC24h)	Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8
The Ratio of the Maximum Plasma Concentration (Peak) to Trough Observed Concentration (Peak/Trough Ratio)	Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events as a Measure of Safety and Tolerability	Screening up to follow-up (in part 1 and part 2 [approximately up to 8 weeks])

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Triana-Baltzer G, Timmers M, De Boer P, Schoene M, Furey M, Bleys C, Vrancken I, Slemmon R, Ceusters M, van Nueten L, Kolb H. Profiling classical neuropsychiatric biomarkers across biological fluids and following continuous lumbar puncture: A guide to sample type and time. Compr Psychoneuroendocrinol. 2022 Jan 15;10:100116. doi: 10.1016/j.cpnec.2022.100116. eCollection 2022 May.

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: September 21, 2016
• First Submitted That Met QC Criteria: October 12, 2016
• First Posted (Estimated): October 14, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 31, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: CR108231; 2016-003040-37 (EudraCT Number); 54175446EDI1005 (Other Identifier: Janssen Research & Development, LLC)