A Study to Evaluate Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Pharmacodynamics of JNJ-64179375 in Healthy Male Subjects

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: JNJ-64179375; Drug: Placebo; Drug: 4 Factor Prothrombin Complex Concentrate (PCC)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02949206

2016-003006-13 (EudraCT Number)

64179375EDI1001 (Other Identifier)

CR108238

Details and patient eligibility

About

The purpose of this study is to assess the safety and tolerability of JNJ-64179375 in Part 1 (Intravenous dose) and Part 3 (Subcutaneous dose) and potential for reversibility of JNJ-64179375 induced Pharmacodynamic effects on coagulation parameters and platelet function (Part 2) in healthy male participants.

Enrollment: 80 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Body mass index [weight kilogram per meter square (kg/m^2)] between 18 and 30 kg/m^2 (inclusive), and body weight greater than 50 kilogram (kg) but less than 100 kg
• Generally in good health on the basis of physical examination, medical history, vital signs, laboratory tests, and electrocardiogram (ECG) 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
• contraceptive use by men should be consistent with local regulations regarding the use of contraceptive methods for subject participating in clinical studies
• willing and able to adhere to the study visit schedule and other requirements, prohibitions, and restrictions specified in this protocol through the Day 113 visit

Exclusion criteria

• 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 values for coagulation, hematology, clinical chemistry or urinalysis at screening or on Day -1 (at admission to the clinical research unit) as determined by the investigator or appropriate designee
• Have smoked tobacco or nicotine-related products within 6 months prior to dosing or does not agree to refrain through Day 113
• Donated blood or blood products or had substantial loss of blood [more than 500 milliliter (mL)] within 3 months before the first administration of study drug or intends to donate or donates blood or blood products during the study until 30 days after completion
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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80 participants in 10 patient groups

Part 1: Cohort 1 (0.03 mg/kg of JNJ-64179375 or Placebo)

Experimental group

Description:

Participants in a ratio of 3:1 will receive a single 0.03 milligram per kilogram (mg/kg) intravenous (IV) dose of JNJ-64179375 or matching placebo on Day 1.

Treatment:

Drug: JNJ-64179375

Drug: Placebo

Part 1: Cohort 2 (0.1 mg/kg of JNJ-64179375 or Placebo)

Experimental group

Description:

Participants in a ratio of 3:1 will receive a single 0.1 mg/kg IV dose of JNJ-64179375 or matching placebo on Day 1.

Treatment:

Drug: JNJ-64179375

Drug: Placebo

Part 1: Cohort 3 (0.3 mg/kg of JNJ-64179375 or Placebo)

Experimental group

Description:

Participants in a ratio of 3:1 will receive a single 0.3 mg/kg IV dose of JNJ-64179375 or matching placebo on Day 1.

Treatment:

Drug: JNJ-64179375

Drug: Placebo

Part 1: Cohort 4 (1.0 mg/kg of JNJ-64179375 or Placebo)

Experimental group

Description:

Participants in a ratio of 3:1 will receive a single 1.0 mg/kg IV dose of JNJ-64179375 or matching placebo on Day 1.

Treatment:

Drug: JNJ-64179375

Drug: Placebo

Part 1: Cohort 5 (2.5 mg/kg of JNJ-64179375 or Placebo)

Experimental group

Description:

Participants in a ratio of 3:1 will receive a single 2.5 mg/kg IV dose of JNJ-64179375 or matching placebo on Day 1.

Treatment:

Drug: JNJ-64179375

Drug: Placebo

Part 1: Cohort 6 (5.0 mg/kg of JNJ-64179375 or Placebo)

Experimental group

Description:

Participants in a ratio of 3:1 will receive a single 5.0 mg/kg IV dose of JNJ-64179375 or matching placebo on Day 1.

Treatment:

Drug: JNJ-64179375

Drug: Placebo

Part 1: Cohort 7 (Escalation Dose of JNJ-64179375 or Placebo)

Experimental group

Description:

Dose escalation will proceed until the toxicology study exposure limits or a highest tolerable dose will be reached.

Treatment:

Drug: JNJ-64179375

Drug: Placebo

Part 1: Cohort 8 (Escalation Dose of JNJ-64179375 or Placebo)

Experimental group

Description:

Dose escalation will proceed until the toxicology study exposure limits or a highest tolerable dose will be reached.

Treatment:

Drug: JNJ-64179375

Drug: Placebo

Part 2: Reversal Cohort :(50 IU/kg of 4-factor PCC)

Experimental group

Description:

Participants will receive a 2.5 mg/kg of JNJ-64179375 or highest tolerable dose if lower than 2.5 mg/kg followed by administration of a single IV 50 International Unit per kilogram (IU/Kg) dose of a 4 factor prothrombin complex concentrate (PCC) or matching placebo on Day 1.

Treatment:

Drug: JNJ-64179375

Drug: Placebo

Drug: 4 Factor Prothrombin Complex Concentrate (PCC)

Part 3: Subcutaneous Cohort (1.0 mg/kg of JNJ-64179375)

Experimental group

Description:

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.

Treatment:

Drug: JNJ-64179375

Drug: Placebo