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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: JNJ-64232025 IV
* Drug: JNJ-64232025 SC
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 |