A Study to Evaluate the Safety and Efficacy of Intravenous JNJ-64179375 Versus Oral Apixaban in Participants Undergoing Elective Total Knee Replacement Surgery

JRCT ID: jRCT2080223833

Registered date:05/03/2018

Basic Information

• Health condition(s) or Problem(s) studied: VTE prophylaxis with anticoagulation after Total Knee Replacement surgery
• Date of first enrollment: 05/03/2018
• Target sample size: 150
• Study type: Interventional

Intervention(s)

investigational material(s)
Generic name etc : JNJ-64179375
INN of investigational material :
Therapeutic category code : 333 Anticoagulants
Dosage and Administration for Investigational material : Part 1 : Subjects will be administrated a single-ascending IV dose of JNJ-64179375 or apixaban 2.5 mg given orally twice daily for 10 to 14 days. The administration of the study drugs will begin the day after the TKR surgery, within a minimum of 12 hours and a maximum of 24 hours after the end of the TKR surgery. JNJ-64179375 will be administered in a dose-escalation manner, with planned doses of 0.3, 0.6, and 1.2 mg/kg in Cohorts 1, 2, and 3, respectively. Doses within the optional cohorts will either be new doses within the range of 0.1 to 1.8 mg/kg, or doses from the preceding cohorts. JNJ-64179375 placebo (saline) will be administered in the Apixaban group. Part 2: Subjects will be administrated a single-ascending IV dose of JNJ-64179375 /placebo(saline) or apixaban 2.5 mg/placebo given orally twice daily for 10 to 14 days. 4 dose levels of JNJ-64179375 will be determined in the Part1.

control material(s)
Generic name etc : Apixaban
INN of investigational material : Apixaban
Therapeutic category code : 333 Anticoagulants
Dosage and Administration for Investigational material : Part 1 : Subjects will be administrated a single-ascending IV dose of JNJ-64179375 or apixaban 2.5 mg given orally twice daily for 10 to 14 days. The administration of the study drugs will begin the day after the TKR surgery, within a minimum of 12 hours and a maximum of 24 hours after the end of the TKR surgery. JNJ-64179375 will be administered in a dose-escalation manner, with planned doses of 0.3, 0.6, and 1.2 mg/kg in Cohorts 1, 2, and 3, respectively. Doses within the optional cohorts will either be new doses within the range of 0.1 to 1.8 mg/kg, or doses from the preceding cohorts. JNJ-64179375 placebo (saline) will be administered in the Apixaban group. Part 2: Subjects will be administrated a single-ascending IV dose of JNJ-64179375 /placebo(saline) or apixaban 2.5 mg/placebo given orally twice daily for 10 to 14 days. 4 dose levels of JNJ-64179375 will be determined in the Part1.

Outcome(s)

Primary Outcome

Number of Participants With any Bleeding Event (Part 1)
Baseline up to Day 10-14 Visit
Number of Participants With any Bleeding Event (Part 2)
Baseline up to Day 10-14 Visit
Number of Participants With Total Venous Thromboembolism (VTE) (Part 1)
Baseline up to Day 10-14 Visit
Number of Participants With Total Venous Thromboembolism (VTE) (Part 2)
Baseline up to Day 10-14 Visit

Secondary Outcome

Number of Participants With any Bleeding Event (Part 1 and Part 2)
Through Week 18
Number of Participants With Total VTE (Part 1 and Part 2)
Through Week 18
Number of Participants With Major Bleeding Events (Part 1 and Part 2)
Through Week 18
Number of Participants With Clinically Relevant Nonmajor Bleeding Events (Part 1 and Part 2)
Through Week 18
Number of Participants With Minimal Bleeding Events (Part 1 and Part 2)
Through Week 18
Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding Events (Part 1 and Part 2)
Through Week 18
Number of Participants With Major VTE (Part 1 and Part 2)
Through Week 18
Number of Participants With Proximal and Distal Deep Vein Thrombosis (DVT) (Part 1 and Part 2)
Through Week 18
Number of Participants With any Wound or Joint Complication in the Operated leg (Part 1 and Part 2)
Through Week 18
Number of Participants With Nonfatal Pulmonary Embolism (PE) (Part 1 and Part 2)
Through Week 18
Number of Participants With Death (Part 1 and Part 2)
Through Week 18

Key inclusion & exclusion criteria

• Age minimum: >= 50age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Weight greater than or equal to (>=) 40 kg to less than or equal to (<=) 150 kilogram (kg)
- Medically appropriate for postoperative anticoagulant prophylaxis as determined by the investigator
- Has undergone an elective primary unilateral total knee replacement (TKR)
- Before randomization, a woman must not be of childbearing potential defined as postmenopausal (defined as no menses for 12 months without an alternative medical cause) and/ or permanently sterile (include
hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy)
- Contraceptive use by men should be consistent with local regulations regarding the use of contraceptive methods for participant participating in clinical studies

Exclude criteria

- Any condition for which the use of apixaban is not recommended in the opinion of the investigator
- Bilateral, revision or unicompartmental procedure
- Known or suspected hypersensitivity or intolerance to any biologic medication or known allergies or clinically significant reactions to murine, chimeric, or human proteins, monoclonal antibodies or antibody fragments, or any of the excipients of JNJ-64179375
- Unable to undergo venography
- Known previous deep vein thrombosis (DVT) in either lower extremity

Related Information

• Primary Sponsor: Janssen Pharmaceutical K.K.
• Secondary ID(s): JapicCTI-183889