A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of JNJ-64232025 in Healthy Participants

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of JNJ-64232025 in Healthy Participants

The purpose of this study is to assess the safety and tolerability of JNJ-64232025 following single ascending intravenous (IV) study intervention administrations and a single subcutaneous (SC) intervention administration in healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: JNJ-64232025 IV; Drug: Placebo; Drug: JNJ-64232025 SC

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2060
    • SGS Life Science Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female of non-childbearing potential (postmenopausal or permanently sterile)
• Have a body mass index (BMI) between 19 and 30 kilogram per meter square (kg/m^2) (BMI = weight/height^2), and a body weight of 50 to 100 kilogram (kg), inclusive
• Healthy on the basis of medical history, a physical examination, vital signs, and 12 lead electrocardiogram (ECG) performed at screening
• Healthy on the basis of clinical laboratory tests performed at screening and Day -1
• A woman must have a negative highly sensitive serum pregnancy test at screening and a negative urine pregnancy test on Day -1

Exclusion Criteria:

• Has history of any clinically significant medical illness or medical disorders the investigator considers should exclude the participant, including (but not limited to), neuromuscular, hematological disease, immune deficiency state, respiratory disease, hepatic or gastrointestinal disease, neurological or psychiatric disease, ophthalmological disorders, neoplastic disease, renal or urinary tract diseases, or dermatological disease
• Has a disease or disease treatment associated with immune suppression or lymphopenia, these include but are not limited to bone marrow or organ transplantation, lymphoproliferative disorders, T- or B-cell deficiency syndromes, splenectomy, functional asplenism, and chronic granulomatous disease
• Has a personal history of or conditions associated with thromboembolic events or bleeding disorders, including (but not limited to) myocardial infarction (MI), cerebral vascular accident (CVA)/stroke, deep vein thrombosis (DVT), pulmonary embolism (PE), hemophilia, or menometrorrhagia
• Has history of allergy or adverse reactions to shellfish, aluminum, aluminum hydroxide keyhole limpet hemocyanin (KLH), tetanus or tetanus toxoid or its excipients
• Has a known or suspected intolerance or hypersensitivity to any biologic medication or known allergies or clinically significant reactions to murine, chimeric, or human proteins, monoclonal antibodies or antibody fragments, or to any components of the formulation of JNJ-64232025 and its excipients used in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single Ascending Dose (SAD) IV Cohort; Participants will receive single intravenous (IV) dose of JNJ-64232025 or placebo in Cohorts 1 to 6 on Day 1.	Drug: JNJ-64232025 IV; JNJ-64232025 will be administered as IV infusion.; Drug: Placebo; Matching placebo will be administered as IV infusion or SC injection.
EXPERIMENTAL: Subcutaneous (SC) Cohort; Participants will receive single dose of JNJ-64232025 or placebo as SC injection.	Drug: Placebo; Matching placebo will be administered as IV infusion or SC injection.; Drug: JNJ-64232025 SC; JNJ-64232025 will be administered as SC injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Treatment-Emergent Adverse Events (TEAE) by Severity	An adverse event (AE) is any untoward medical occurrence in a participant who receive study drug without regard to possibility of causal relationship. The severity of the TEAEs will be assessed as mild, moderate, or severe.	Up to Day 113
Number of Participants with Serious Adverse Events (SAE)	An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Up to Day 113
Number of Participants with Clinically Significant Changes in Vital Signs	Number of participants with clinically significant changes in the vital signs including temperature, pulse/heart rate, respiratory rate, and blood pressure will be reported.	Up to Day 113
Number of Participants with ECG Abnormalities	Number of participants with electrocardiogram (ECG) abnormalities will be reported.	Up to Day 113
Number of Participants with Clinical Laboratory Abnormalities	Number of participants with clinical laboratory abnormalities, including cytomegalovirus (CMV) and Epstein-Barr virus (EBV) viral loads, will be reported.	Up to Day 113

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of JNJ-64232025	The Cmax is the maximum observed plasma concentration of JNJ-64232025.	Up to Day 113
Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-64232025	The Tmax is defined as actual sampling time to reach maximum observed plasma concentration of JNJ-64232025.	Up to Day 113
Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity with Extrapolation of the Terminal Phase (AUC[0-infinity])	The AUC(0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(0-last)/lambda(z); wherein AUC(0-last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(0-last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.	Up to Day 113
Area Under the Plasma Concentration-Time Curve from Time Zero to the Time Corresponding to the Last Quantifiable Concentration (AUC[0-last])	The AUC(0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.	Up to Day 113
Terminal Half-Life (t1/2)	The t1/2 is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).	Up to Day 113
Total Systemic Clearance (C/L)	Systemic clearance is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma AUC(0-infinity).	Up to Day 113
Apparent Total Systemic Clearance After Extravascular Administration (CL/F)	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F is the apparent total systemic clearance after extravascular administration.	Up to Day 113
Volume of Distribution Based on Terminal Phase (Vz)	Volume of distribution 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.	Up to Day 113
Apparent Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F)	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after subcutaneous dose (Vz/F) is influenced by the fraction absorbed.	Up to Day 113
Relative SC Bioavailability (F%)	Relative SC bioavailability will be calculated using the following equation: F (%[percent]) = AUC(0-infinity),SC/ mean AUC(0-infinity),IV *100%.	Up to Day 113
Number of Participants with Anti-JNJ 64232025 Antibodies	Number of participants with anti-JNJ-64232025 antibodies will be assessed.	Up to Day 113
Number of Participants with Anti-KLH and Anti-Tetanus Antibodies	Number of participants with antibodies to anti-Keyhole Limpet Hemocyanin (KLH) and anti-tetanus will be assessed.	Up to Day 113

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2018
• Primary Completion (ACTUAL): February 5, 2019
• Study Completion (ACTUAL): February 5, 2019

Study Registration Dates

• First Submitted: May 29, 2018
• First Submitted That Met QC Criteria: May 29, 2018
• First Posted (ACTUAL): June 11, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 27, 2019
• Last Update Submitted That Met QC Criteria: February 26, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: CR108448; 2017-003986-82 (EUDRACT_NUMBER); 64232025ARA1001 (OTHER: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No