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

Phase 1CompletedNCT03080987

Janssen Research & Development, LLC40 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Healthy

Interventions

JNJ-64179375 0.3 mg/kgDRUG

JNJ-64179375 0.3 milligram per kilogram (mg/kg) intravenous (IV) infusion on Day 1.

JNJ-64179375 1.0 mg/kgDRUG

JNJ-64179375 1.0 mg/kg on Day 1 administered as IV infusion (for Part 1) and SC injection (for Part 2).

JNJ-64179375 2.5 mg/kgDRUG

JNJ-64179375 2.5 mg/kg IV infusion on Day 1.

Eligibility

Sex: ALLMin age: 20 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (2)

Souseikai Hakata Clinic

Fukuoka, Japan

Hammersmith Medicines Research Ltd

London, United Kingdom

Outcomes

Primary Outcomes

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.

Time frame: Up to Day 113

Part 2: Number of Participants With Adverse Events as a Measure of Safety and Tolerability

Time frame: Up to Day 113

Secondary Outcomes

Part 1 and 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-64179375

Cmax is the maximum observed plasma concentration.

Time frame: 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.

Time frame: 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.

Time frame: 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

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Matching placebo on Day 1 administered as IV infusion (for Part 1) and SC injection (for Part 2).

JNJ-64179375 (Dose to be Determined)DRUG

JNJ-64179375 IV infusion (Dose to be determined).

CL is defined as total systemic clearance after intravenous administration of JNJ-64179375.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: Predose, Day 1, 2,4, 7, 10, 14, 22, 29,43, 57, 85 and 113 post-dose