A Study to Assess the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Pharmacodynamics of JNJ-64179375 in Healthy Japanese Participants

Study Overview
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Brief Summary
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The primary purpose of this study is to assess the safety and tolerability of JNJ-64179375 in Part 1 and 2.

Official Title
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A 2-Part Study to Assess the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Pharmacodynamics of JNJ-64179375 in Healthy Japanese Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: JNJ-64179375 0.3 mg/kg
* Drug: JNJ-64179375 1.0 mg/kg
* Drug: JNJ-64179375 2.5 mg/kg
* Other: Placebo
* Drug: JNJ-64179375 (Dose to be Determined)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have been born in Japan of Japanese parents and maternal and paternal Japanese grandparents Body mass index (weight kg/m^2) between 18 and 27 kilogram per square meter (kg/m^2) (inclusive), and body weight greater than 50 kg but less than 100 kg Generally in good health on the basis of physical examinations, medical history, vital signs, laboratory tests, electrocardiograms (ECGs) and cardiac telemetry performed at Screening and/or prior to administration of the initial dose of study drug Must sign an informed consent form (ICF) indicating that he understands the purpose of, and procedures required for, the study and is willing to participate in the study Exclusion Criteria: History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, bleeding or thrombotic disorders (including any personal or family history of abnormal bleeding as assessed by a detailed bleeding history or blood dyscrasias), or with an underlying coagulopathy that may lead to a clinically relevant bleeding risk, autoimmune disease, lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the investigator considers should exclude the subject or that could interfere with the interpretation of the study results Acute illness, including an upper respiratory infection (with or without fever), within 7 days prior to study drug administration or have had a major illness or hospitalization within 1 month prior to study drug administration Clinically significant abnormal physical exam at Screening or Day -1 Clinically significant abnormal vital signs at Screening, Day -1, or Day 1 (predose) as determined by the investigator or appropriate designee Clinically significant abnormal cardiac telemetry, or ECG at Screening, Day -1, or Day 1 (predose) as determined by the investigator or appropriate designee

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Cohort 1 (0.3 mg/kg of JNJ-64179375 or Placebo)<br>Participants will receive a single 0.3 milligram per kilogram (mg/kg) intravenous (IV) dose of JNJ-64179375 or matching Placebo on Day 1. | Drug: JNJ-64179375 0.3 mg/kg<br>* JNJ-64179375 0.3 milligram per kilogram (mg/kg) intravenous (IV) infusion on Day 1.<br>Other: Placebo<br>* Matching placebo on Day 1 administered as IV infusion (for Part 1) and SC injection (for Part 2).<br>|
| Experimental: Part 1: Cohort 2 (1.0 mg/kg of JNJ-64179375 or Placebo)<br>Participants will receive a single 1.0 mg/kg IV dose of JNJ-64179375 or matching Placebo on Day 1. | Drug: JNJ-64179375 1.0 mg/kg<br>* JNJ-64179375 1.0 mg/kg on Day 1 administered as IV infusion (for Part 1) and SC injection (for Part 2).<br>Other: Placebo<br>* Matching placebo on Day 1 administered as IV infusion (for Part 1) and SC injection (for Part 2).<br>|
| Experimental: Part 1: Cohort 3 (2.5 mg/kg of JNJ-64179375 or Placebo)<br>Participants will receive a single 2.5 mg/kg IV dose of JNJ-64179375 or matching Placebo on Day 1. | Drug: JNJ-64179375 2.5 mg/kg<br>* JNJ-64179375 2.5 mg/kg IV infusion on Day 1.<br>Other: Placebo<br>* Matching placebo on Day 1 administered as IV infusion (for Part 1) and SC injection (for Part 2).<br>|
| Experimental: Part 1: Optional Cohort 1 (JNJ-64179375 or Placebo)<br>Participants will receive a single IV dose of JNJ-64179375 (dose to be determined) or matching Placebo on Day 1. | Other: Placebo<br>* Matching placebo on Day 1 administered as IV infusion (for Part 1) and SC injection (for Part 2).<br>Drug: JNJ-64179375 (Dose to be Determined)<br>* JNJ-64179375 IV infusion (Dose to be determined).<br>|
| Experimental: Part 1: Optional Cohort 2 (JNJ-64179375 or Placebo)<br>Participants will receive a single IV dose of JNJ-64179375 (dose to be determined) or matching Placebo on Day 1. | Other: Placebo<br>* Matching placebo on Day 1 administered as IV infusion (for Part 1) and SC injection (for Part 2).<br>Drug: JNJ-64179375 (Dose to be Determined)<br>* JNJ-64179375 IV infusion (Dose to be determined).<br>|
| Experimental: Part 2: SC Cohort (1.0 mg/kg of JNJ-64179375 or Placebo)<br>Participants will receive a single subcutaneous (SC) dose of 1.0 mg/kg or highest tolerable dose if less than 1.0 mg/kg of JNJ-64179375 or matching Placebo on Day 1. | Drug: JNJ-64179375 1.0 mg/kg<br>* JNJ-64179375 1.0 mg/kg on Day 1 administered as IV infusion (for Part 1) and SC injection (for Part 2).<br>Other: Placebo<br>* Matching placebo on Day 1 administered as IV infusion (for Part 1) and SC injection (for Part 2).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of Participants With Adverse Events as a Measure of Safety and Tolerability | An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. | Up to Day 113 | 
| Part 2: Number of Participants With Adverse Events as a Measure of Safety and Tolerability | An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. | Up to Day 113 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 and 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-64179375 | Cmax is the maximum observed plasma concentration. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 post-dose | 
| Part 1 and 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) of JNJ-64179375 | The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 post-dose | 
| Part 1 and 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of JNJ-64179375 | The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 post-dose | 
| Part 1: Total Systemic Clearance (CL) of JNJ-64179375 | CL is defined as total systemic clearance after intravenous administration of JNJ-64179375. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 post-dose | 
| Part 1: Apparent Volume of Distribution at Terminal Phase After Intravenous Administration (Vz) of JNJ-64179375 | Vz is defined as the Apparent volume of distribution at terminal phase after intravenous administration. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 post-dose | 
| Part 1 and 2: Terminal Half-Life (t1/2) of JNJ-64179375 | Half-life is the time measured for the plasma concentration of drug to decrease by one half. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 post-dose | 
| Part 2: Total Systemic Clearance Over Bioavailability After Subcutaneous (SC) Administration (CL/F) of JNJ-64179375 post-dose | CL/F is defined as total systemic clearance over bioavailability after SC administration. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 post-dose | 
| Part 2: Apparent Volume of Distribution at Terminal Phase Over Bioavailability After Subcutaneous Administration (Vz/F) of JNJ-64179375 | (Vz/F) is defined as Apparent Volume of distribution at terminal phase over bioavailability after SC administration of JNJ-64179375. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 post-dose | 
| Part 2: Absolute Bioavailability (F) After Subcutaneous Administration of JNJ-64179375 | F is defined as absolute bioavailability after SC administration of JNJ-64179375. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 post-dose | 
| Part 1 and 2: Immunogenicity of JNJ-64179375 | Plasma samples will be collected and screened for antibodies binding to JNJ-64179375 and the titer of confirmed positive samples will be reported. | Predose, Day 7, 14, 29, 57, 85 and 113 post-dose | 
| Part 1 and 2: Pharmacodynamic Effect of JNJ-64179375 as Assessed by Change in Thrombin Time (TT) | The pharmacodynamic effect of JNJ-64179375 on coagulation parameters will be assessed by measuring the change in thrombin time (TT). | Predose, Day 1, 2, 4, 7, 14, 29, 57 and 113 post-dose | 
| Part 1 and 2: Pharmacodynamic Effect of JNJ-64179375 as Assessed by Change in Prothrombin Time (PT) | The pharmacodynamic effect of JNJ-64179375 on coagulation parameters will be assessed by measuring the change in prothrombin time (PT). | Predose, Day 1, 2, 4, 7, 14, 29, 57 and 113 post-dose | 
| Part 1 and 2: Pharmacodynamic Effect of JNJ-64179375 as Assessed by Change in Activated Partial Thromboplastin time (aPTT) | The pharmacodynamic effect of JNJ-64179375 on coagulation parameters will be assessed by measuring the change in activated partial thromboplastin time (aPTT). | Predose, Day 1, 2, 4, 7, 14, 29, 57 and 113 post-dose | 
| Part 1 and 2: Pharmacodynamic Effect of JNJ-64179375 as Assessed by Change in Ecarin Clotting time (ECT) | The pharmacodynamic effect of JNJ-64179375 on coagulation parameters will be assessed by measuring the change in Ecarin Clotting time (ECT). | Predose, Day 1, 2, 4, and 14 post-dose | 
| Part 1 and 2: Pharmacodynamic Effect of JNJ-64179375 on Platelet Function | Platelet function will be assessed by measuring platelet activation and aggregation in response to thrombin and other agonists and with the platelet function analyzer (PFA)100. | Predose, Days 1 and 14 post-dose | 
| Part 1 and 2: Pharmacodynamic Effect of JNJ-64179375 as Assessed by Thrombin Generation Assay (TGA) | The TGA is based on the premise that measurements of thrombin generation are indicative of the overall coagulating capacity of the individual. | Predose, Day 1 and 14 post-dose | 
| Part 1 and 2: Pharmacodynamic Effect of JNJ-64179375 as Assessed by D-dimer | The D-dimer assay is an enzyme immunoassay procedure for the quantitative determination of D-dimer. | Predose, Day 1 and 14 post-dose | 
| Part 1 and 2: Pharmacodynamic Effect of JNJ-64179375 as Assessed by Change in International Normalized Ratio (INR) | The pharmacodynamic effect of JNJ-64179375 on coagulation parameters will be assessed by measuring the change in international normalized ratio (INR). | Predose, Day 1, 2,4, 7, 14, 29, 57 and 113 post-dose | 
| Part 2: Time to Maximum Observed Plasma Concentration (Tmax) After Subcutaneous Administration of JNJ-64179375 | The Tmax is defined as actual sampling time to reach maximum observed plasma concentration. | Predose, Day 1, 2,4, 7, 10, 14, 22, 29,43, 57, 85 and 113 post-dose |