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

NCT02949206 | Completed Phase 1

• 3 other identifiers: CR10823864179375EDI10012016-003006-13
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• Part 1: Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability

  Up to Day 113

• Part 3: Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability

  Up to Day 113

• Part 2: Change From Baseline in Potential for Reversibility of the JNJ-64179375 Induced Pharmacodynamic Effects on Coagulation Parameters

  Change in Potential for Reversibility of the JNJ-64179375 will be assessed by assessing the change in thrombin time as coagulation parameter.

  Baseline and Day 1

• Part 2: Change From Baseline in Potential for Reversibility of the JNJ-64179375 Induced Pharmacodynamic Effects 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.

  Baseline and Day 1

Secondary Outcomes (21)

• Part 1 and 3: Maximum Observed Plasma Concentration (Cmax) of JNJ-64179375

  Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113

• Part 1 and 3: Area Under the Plasma Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of JNJ-64179375

  Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113

• Part 1 and 3: 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

• Part 1 and 3: Terminal Half-Life (t1/2) of JNJ-64179375

  Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113

• Part 1: Total Systemic Clearance (CL) of JNJ-64179375

  Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113

Study Arms (10)

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

EXPERIMENTAL

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.

Drug: JNJ-64179375; Drug: Placebo

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

EXPERIMENTAL

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.

Drug: JNJ-64179375; Drug: Placebo

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

EXPERIMENTAL

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.

Drug: JNJ-64179375; Drug: Placebo

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

EXPERIMENTAL

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.

Drug: JNJ-64179375; Drug: Placebo

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

EXPERIMENTAL

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.

Drug: JNJ-64179375; Drug: Placebo

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

EXPERIMENTAL

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.

Drug: JNJ-64179375; Drug: Placebo

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

EXPERIMENTAL

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

Drug: JNJ-64179375; Drug: Placebo

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

EXPERIMENTAL

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

Drug: JNJ-64179375; Drug: Placebo

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

EXPERIMENTAL

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.

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

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

EXPERIMENTAL

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; Drug: Placebo

Interventions

JNJ-64179375 DRUG

During part 1, participants will receive a single ascending Intravenous dose of JNJ-64179375 ranging from (0.03 mg/kg to 5.0 mg/kg). In Part 2, participants will receive a 2.5 mg/kg or highest tolerable dose if lower than 2.5 mg/kg of JNJ-64179375. In Part 3, 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.

Part 1: Cohort 1 (0.03 mg/kg of JNJ-64179375 or Placebo); Part 1: Cohort 2 (0.1 mg/kg of JNJ-64179375 or Placebo); Part 1: Cohort 3 (0.3 mg/kg of JNJ-64179375 or Placebo); Part 1: Cohort 4 (1.0 mg/kg of JNJ-64179375 or Placebo); Part 1: Cohort 5 (2.5 mg/kg of JNJ-64179375 or Placebo); Part 1: Cohort 6 (5.0 mg/kg of JNJ-64179375 or Placebo); Part 1: Cohort 7 (Escalation Dose of JNJ-64179375 or Placebo); Part 1: Cohort 8 (Escalation Dose of JNJ-64179375 or Placebo); Part 2: Reversal Cohort :(50 IU/kg of 4-factor PCC); Part 3: Subcutaneous Cohort (1.0 mg/kg of JNJ-64179375)

Placebo DRUG

Participants will randomly receive matching placebo in all 3 Parts on day 1 administered via IV Route (for Part 1 and 2) and SC route (for Part 3).

Part 1: Cohort 1 (0.03 mg/kg of JNJ-64179375 or Placebo); Part 1: Cohort 2 (0.1 mg/kg of JNJ-64179375 or Placebo); Part 1: Cohort 3 (0.3 mg/kg of JNJ-64179375 or Placebo); Part 1: Cohort 4 (1.0 mg/kg of JNJ-64179375 or Placebo); Part 1: Cohort 5 (2.5 mg/kg of JNJ-64179375 or Placebo); Part 1: Cohort 6 (5.0 mg/kg of JNJ-64179375 or Placebo); Part 1: Cohort 7 (Escalation Dose of JNJ-64179375 or Placebo); Part 1: Cohort 8 (Escalation Dose of JNJ-64179375 or Placebo); Part 2: Reversal Cohort :(50 IU/kg of 4-factor PCC); Part 3: Subcutaneous Cohort (1.0 mg/kg of JNJ-64179375)

4 Factor Prothrombin Complex Concentrate (PCC) DRUG

Following a single dose of JNJ-64179375, participants will receive a single IV dose of 4 factor-PCC.

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

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Unknown Facility

Merksem, Belgium

Location

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2016
• First Posted: October 31, 2016
• Study Start: November 14, 2016
• Primary Completion: August 9, 2017
• Study Completion: August 9, 2017
• Last Updated: September 25, 2017

Record last verified: 2017-09

Locations

BE (1)