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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: JNJ-64179375 0.3 mg/kg; Drug: JNJ-64179375 2.5 mg/kg; Drug: JNJ-64179375 1.0 mg/kg; Other: Placebo; Drug: JNJ-64179375 (Dose to be Determined)

• Registration Number: NCT03080987
• Lead Sponsor: Janssen Research & Development, LLC

Brief Summary

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

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-03-10
• Study First Submitted QC: 2017-03-10
• Study First Posted: 2017-03-15
• Study Start: 2017-06-27
• Primary Completion: 2018-06-25
• Study Completion: 2018-06-25
• Status Verified: 2018-10
• Last Update Submitted: 2018-10-12
• Last Update Posted: 2018-10-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part 1: Cohort 1 (0.3 mg/kg of JNJ-64179375 or Placebo)	JNJ-64179375 0.3 mg/kg	Participants will receive a single 0.3 milligram per kilogram (mg/kg) intravenous (IV) dose of JNJ-64179375 or matching Placebo on Day 1.
Part 1: Cohort 3 (2.5 mg/kg of JNJ-64179375 or Placebo)	JNJ-64179375 2.5 mg/kg	Participants will receive a single 2.5 mg/kg IV dose of JNJ-64179375 or matching Placebo on Day 1.
Part 2: SC Cohort (1.0 mg/kg of JNJ-64179375 or Placebo)	JNJ-64179375 1.0 mg/kg	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.
Part 1: Cohort 1 (0.3 mg/kg of JNJ-64179375 or Placebo)	Placebo	Participants will receive a single 0.3 milligram per kilogram (mg/kg) intravenous (IV) dose of JNJ-64179375 or matching Placebo on Day 1.
Part 1: Cohort 2 (1.0 mg/kg of JNJ-64179375 or Placebo)	JNJ-64179375 1.0 mg/kg	Participants will receive a single 1.0 mg/kg IV dose of JNJ-64179375 or matching Placebo on Day 1.
Part 1: Cohort 2 (1.0 mg/kg of JNJ-64179375 or Placebo)	Placebo	Participants will receive a single 1.0 mg/kg IV dose of JNJ-64179375 or matching Placebo on Day 1.
Part 1: Optional Cohort 1 (JNJ-64179375 or Placebo)	Placebo	Participants will receive a single IV dose of JNJ-64179375 (dose to be determined) or matching Placebo on Day 1.
Part 1: Optional Cohort 2 (JNJ-64179375 or Placebo)	Placebo	Participants will receive a single IV dose of JNJ-64179375 (dose to be determined) or matching Placebo on Day 1.
Part 1: Cohort 3 (2.5 mg/kg of JNJ-64179375 or Placebo)	Placebo	Participants will receive a single 2.5 mg/kg IV dose of JNJ-64179375 or matching Placebo on Day 1.
Part 1: Optional Cohort 2 (JNJ-64179375 or Placebo)	JNJ-64179375 (Dose to be Determined)	Participants will receive a single IV dose of JNJ-64179375 (dose to be determined) or matching Placebo on Day 1.
Part 2: SC Cohort (1.0 mg/kg of JNJ-64179375 or Placebo)	Placebo	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.
Part 1: Optional Cohort 1 (JNJ-64179375 or Placebo)	JNJ-64179375 (Dose to be Determined)	Participants will receive a single IV dose of JNJ-64179375 (dose to be determined) or matching Placebo on Day 1.

Primary Outcome Measures

Name	Time	Method
Part 1: Number of Participants With Adverse Events as a Measure of Safety and Tolerability	Up to Day 113	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.
Part 2: Number of Participants With Adverse Events as a Measure of Safety and Tolerability	Up to Day 113	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.

Secondary Outcome Measures

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

Trial Locations

Locations (2)

Hammersmith Medicines Research Ltd; 🇬🇧 London, United Kingdom

Souseikai Hakata Clinic; 🇯🇵 Fukuoka, Japan