A Randomized, Double-blind, Double-dummy, Multicenter, Adaptive Design, Dose Escalation (Part 1) and Dose-Response (Part 2) Study to Evaluate the Safety and Efficacy of Intravenous JNJ-64179375 Versus Oral Apixaban in Subjects Undergoing Elective Total Knee Replacement Surgery
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 308
- 试验地点
- 103
- 主要终点
- Number of Participants With Treatment-emergent Bleeding Events (Clinical Events Committee [CEC]- Adjudicated)
研究概览
简要总结
The primary purpose of Part 1 in this study is to assess the safety and tolerability of JNJ-64179375 for each dose level for dose escalation and any bleeding events (the composite of major, clinically relevant non-major, and minimal bleeding events) for the selection of doses for Part 2. The primary purpose of Part 2 is to assess the efficacy dose response of JNJ-64179375 for the prevention of total venous thromboembolism (VTE) (proximal and/or distal deep vein thrombosis [DVT] [asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic], nonfatal pulmonary embolism [PE], or any death).
详细描述
This study has 2 parts, dose escalation and dose-response evaluation, and will be conducted in participants undergoing primary unilateral elective Total Knee Replacement (TKR) surgery. Participants will participate in either Part 1 or Part 2 of study only. The study will be conducted in 3 phases: an up to 30-day screening phase before surgery, a 14-day double-blind dosing phase, and a 16-week follow-up phase. Safety evaluations will include monitoring of all nonserious and serious adverse events, clinical laboratory tests, vital signs measurements, and physical examinations. Pharmacokinetics (dense and sparse), pharmacodynamic (PD), health resource utilization, and immunogenicity samples will also be assessed. The total study duration of participant's participation in Part 1 or part 2 after randomization will be approximately 18 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Part 1: Cohort 3 (1.2 mg/kg JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 1.2 mg/kg IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: Apixaban 2.5 mg (Drug)
Part 1: Optional Cohort 4 (JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 Dose to be determined (TBD) based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: JNJ-64179375 (Dose to be Determined) (Drug)
Part 1: Optional Cohort 4 (JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 Dose to be determined (TBD) based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: Placebo JNJ-64179375 (Drug)
Part 1: Cohort 1 (0.3 mg/kg JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 0.3 milligram per kilogram (mg/kg) intravenously (IV) or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: JNJ-64179375 0.3 mg/kg (Drug)
Part 1: Cohort 1 (0.3 mg/kg JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 0.3 milligram per kilogram (mg/kg) intravenously (IV) or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: Placebo JNJ-64179375 (Drug)
Part 1: Cohort 1 (0.3 mg/kg JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 0.3 milligram per kilogram (mg/kg) intravenously (IV) or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: Apixaban placebo (Drug)
Part 1: Cohort 1 (0.3 mg/kg JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 0.3 milligram per kilogram (mg/kg) intravenously (IV) or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: Apixaban 2.5 mg (Drug)
Part 1: Cohort 2 (0.6 mg/kg JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 0.6 mg/kg IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: JNJ-64179375 0.6 mg/kg (Drug)
Part 1: Cohort 2 (0.6 mg/kg JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 0.6 mg/kg IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: Placebo JNJ-64179375 (Drug)
Part 1: Cohort 2 (0.6 mg/kg JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 0.6 mg/kg IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: Apixaban placebo (Drug)
Part 1: Cohort 2 (0.6 mg/kg JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 0.6 mg/kg IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: Apixaban 2.5 mg (Drug)
Part 1: Cohort 3 (1.2 mg/kg JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 1.2 mg/kg IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: JNJ-64179375 1.2 mg/kg (Drug)
Part 1: Cohort 3 (1.2 mg/kg JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 1.2 mg/kg IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: Placebo JNJ-64179375 (Drug)
Part 1: Cohort 3 (1.2 mg/kg JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 1.2 mg/kg IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: Apixaban placebo (Drug)
Part 1: Optional Cohort 4 (JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 Dose to be determined (TBD) based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: Apixaban placebo (Drug)
Part 1: Optional Cohort 4 (JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 Dose to be determined (TBD) based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: Apixaban 2.5 mg (Drug)
Part 1: Optional Cohort 5 (JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 Dose TBD based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: JNJ-64179375 (Dose to be Determined) (Drug)
Part 1: Optional Cohort 5 (JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 Dose TBD based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: Placebo JNJ-64179375 (Drug)
Part 1: Optional Cohort 5 (JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 Dose TBD based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: Apixaban placebo (Drug)
Part 1: Optional Cohort 5 (JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 Dose TBD based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: Apixaban 2.5 mg (Drug)
Part 1: Optional Cohort 6 (JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 Dose TBD based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: JNJ-64179375 (Dose to be Determined) (Drug)
Part 1: Optional Cohort 6 (JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 Dose TBD based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: Placebo JNJ-64179375 (Drug)
Part 1: Optional Cohort 6 (JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 Dose TBD based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: Apixaban placebo (Drug)
Part 1: Optional Cohort 6 (JNJ-64179375/Apixaban)
Participants will receive JNJ-64179375 Dose TBD based on preliminary data (dose may range from 0.1 to 1.8 mg/kg or any dose from the preceding cohorts) IV or JNJ-64179375 placebo (saline) IV infusion as a single dose on Day 1 and matching apixaban placebo or 2.5 mg apixaban, orally twice a day for 10 to 14 days.
干预措施: Apixaban 2.5 mg (Drug)
Part 2: Group A: JNJ-64179375 A mg/kg and apixaban placebo
Participants will receive JNJ-64179375 Dose A mg/kg (TBD based on review of data from Part 1) IV as a single dose on Day 1 and apixaban placebo orally twice a day for 10 to 14 days.
干预措施: JNJ-64179375 A mg/kg (Drug)
Part 2: Group A: JNJ-64179375 A mg/kg and apixaban placebo
Participants will receive JNJ-64179375 Dose A mg/kg (TBD based on review of data from Part 1) IV as a single dose on Day 1 and apixaban placebo orally twice a day for 10 to 14 days.
干预措施: Apixaban placebo (Drug)
Part 2: Group B: JNJ-64179375 B mg/kg and apixaban placebo
Participants will receive JNJ-64179375 Dose B mg/kg (TBD based on review of data from Part 1) IV as a single dose on Day 1 and apixaban placebo orally twice a day for 10 to 14 days.
干预措施: JNJ-64179375 B mg/kg (Drug)
Part 2: Group B: JNJ-64179375 B mg/kg and apixaban placebo
Participants will receive JNJ-64179375 Dose B mg/kg (TBD based on review of data from Part 1) IV as a single dose on Day 1 and apixaban placebo orally twice a day for 10 to 14 days.
干预措施: Apixaban placebo (Drug)
Part 2: Group C: JNJ-64179375 C mg/kg and apixaban placebo
Participants will receive JNJ-64179375 Dose C mg/kg (TBD based on review of data from Part 1) IV as a single dose on Day 1 and apixaban placebo orally twice a day for 10 to 14 days.
干预措施: JNJ-64179375 C mg/kg (Drug)
Part 2: Group C: JNJ-64179375 C mg/kg and apixaban placebo
Participants will receive JNJ-64179375 Dose C mg/kg (TBD based on review of data from Part 1) IV as a single dose on Day 1 and apixaban placebo orally twice a day for 10 to 14 days.
干预措施: Apixaban placebo (Drug)
Part 2: Group D: JNJ-64179375 D mg/kg and apixaban placebo
Participants will receive JNJ-64179375 Dose D mg/kg (TBD based on review of data from Part 1) IV as a single dose on Day 1 and apixaban placebo orally twice a day for 10 to 14 days.
干预措施: JNJ-64179375 D mg/kg (Drug)
Part 2: Group D: JNJ-64179375 D mg/kg and apixaban placebo
Participants will receive JNJ-64179375 Dose D mg/kg (TBD based on review of data from Part 1) IV as a single dose on Day 1 and apixaban placebo orally twice a day for 10 to 14 days.
干预措施: Apixaban placebo (Drug)
Part 2: Group E: JNJ-64179375 placebo IV and apixaban 2.5 mg
Participants will receive JNJ-64179375 placebo (saline) IV as a single dose on Day 1 and apixaban 2.5 mg orally twice a day for 10 to 14 days.
干预措施: Placebo JNJ-64179375 (Drug)
Part 2: Group E: JNJ-64179375 placebo IV and apixaban 2.5 mg
Participants will receive JNJ-64179375 placebo (saline) IV as a single dose on Day 1 and apixaban 2.5 mg orally twice a day for 10 to 14 days.
干预措施: Apixaban 2.5 mg (Drug)
结局指标
主要结局
Number of Participants With Treatment-emergent Bleeding Events (Clinical Events Committee [CEC]- Adjudicated)
时间窗: Up to Day 10 to 14 (visit observation period)
Number of participants with treatment-emergent bleeding events (BE) (adjudicated by CEC) were reported. Bleeding event was defined as the composite of major, clinically relevant nonmajor (CRNM), and minimal bleeding events assessed through the Day 10 to 14.
Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated)
时间窗: Up to Day 10 to 14 (visit observation period)
Number of participants with total VTE were reported. Total VTE was defined as the composite of CEC-adjudicated proximal and/or distal deep vein thrombosis (DVT) (asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic), nonfatal pulmonary embolism (PE), or any death assessed through the Day 10 to 14 visit. 1 participant had an asymptomatic distal clot in the non-operated leg which is not counted in the Total VTE and 2 participants had symptomatic proximal clots at the Day 10 to 14 venography and are counted in both the asymptomatic proximal and symptomatic proximal groups.
次要结局
- Number of Participants With Composite of Major and CRNM Bleeding Events (CEC-adjudicated)(Up to Day 10 to 14 (visit observation period))
- Number of Participants With Major Bleeding Event (CEC-adjudicated)(Up to Day 10 to 14 (visit observation period))
- Number of Participants With Clinically Relevant Non-major (CRNM) Bleeding Events (CEC-adjudicated)(Up to Day 10 to 14 (visit observation period))
- Number of Participants With Major Bleeding or CRNM Bleeding Events (CEC-adjudicated)(Up to Day 10 and 14 (visit observation period))
- Number of Participants With Minimal Bleeding Events (CEC-adjudicated)(Up to Day 10 to 14 (visit observation period))
- Number of Participants With Major VTE (CEC-adjudicated)(Up to Day 10 to 14 (visit observation period))
- Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated)(Up to Day 10 to 14 (visit observation period))
- Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated)(Up to Day 10 to 14 (visit observation period))
- Number of Participants With Death (CEC-adjudicated)(Up to Day 10 to 14 (visit observation period))
- Number of Participants With Proximal and Distal DVT (CEC-adjudicated)(Up to Day 10 to 14 (visit observation period))
- Number of Participants With Distal DVT (CEC-adjudicated)(Up to Day 10 to 14 (visit observation period))