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

Janssen (J&J Innovative Medicine)

Status and phase

Completed

Phase 2

Conditions

VTE Prophylaxis With Anticoagulation After Total Knee Replacement Surgery

Treatments

Drug: Apixaban 2.5 mg

Drug: JNJ-64179375 A mg/kg

Drug: JNJ-64179375 C mg/kg

Drug: JNJ-64179375 1.2 mg/kg

Drug: JNJ-64179375 D mg/kg

Drug: JNJ-64179375 0.3 mg/kg

Drug: JNJ-64179375 (Dose to be Determined)

Drug: Apixaban placebo

Drug: JNJ-64179375 0.6 mg/kg

Drug: Placebo JNJ-64179375

Drug: JNJ-64179375 B mg/kg

Study type

Interventional

Funder types

Industry

Identifiers

NCT03251482

64179375THR2001 (Other Identifier)

2016-004550-15 (EudraCT Number)

CR108344

Details and patient eligibility

About

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).

Full description

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.

Enrollment

308 patients

Sex

All

Ages

50+ years old

Volunteers

No Healthy Volunteers

Inclusion 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

Exclusion 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

Trial design

Primary purpose

Prevention

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

308 participants in 11 patient groups

Part 1: Cohort 1 (0.3 mg/kg JNJ-64179375/Apixaban)

Experimental group

Description:

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.

Treatment:

Drug: JNJ-64179375 0.3 mg/kg

Drug: Apixaban placebo

Drug: Apixaban 2.5 mg

Drug: Placebo JNJ-64179375

Part 1: Cohort 2 (0.6 mg/kg JNJ-64179375/Apixaban)

Experimental group

Description:

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.

Treatment:

Drug: Apixaban placebo

Drug: Apixaban 2.5 mg

Drug: Placebo JNJ-64179375

Drug: JNJ-64179375 0.6 mg/kg

Part 1: Cohort 3 (1.2 mg/kg JNJ-64179375/Apixaban)

Experimental group

Description:

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.

Treatment:

Drug: Apixaban placebo

Drug: Apixaban 2.5 mg

Drug: Placebo JNJ-64179375

Drug: JNJ-64179375 1.2 mg/kg

Part 1: Optional Cohort 4 (JNJ-64179375/Apixaban)

Experimental group

Description:

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.

Treatment:

Drug: Apixaban placebo

Drug: Apixaban 2.5 mg

Drug: Placebo JNJ-64179375

Drug: JNJ-64179375 (Dose to be Determined)

Part 1: Optional Cohort 5 (JNJ-64179375/Apixaban)

Experimental group

Description:

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.

Treatment:

Drug: Apixaban placebo

Drug: Apixaban 2.5 mg

Drug: Placebo JNJ-64179375

Drug: JNJ-64179375 (Dose to be Determined)

Part 1: Optional Cohort 6 (JNJ-64179375/Apixaban)

Experimental group

Description:

Treatment:

Drug: Apixaban placebo

Drug: Apixaban 2.5 mg

Drug: Placebo JNJ-64179375

Drug: JNJ-64179375 (Dose to be Determined)

Part 2: Group A: JNJ-64179375 A mg/kg and apixaban placebo

Experimental group

Description:

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.

Treatment:

Drug: Apixaban placebo

Drug: JNJ-64179375 A mg/kg

Part 2: Group B: JNJ-64179375 B mg/kg and apixaban placebo

Experimental group

Description:

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.

Treatment:

Drug: Apixaban placebo

Drug: JNJ-64179375 B mg/kg

Part 2: Group C: JNJ-64179375 C mg/kg and apixaban placebo

Experimental group

Description:

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.

Treatment:

Drug: Apixaban placebo

Drug: JNJ-64179375 C mg/kg

Part 2: Group D: JNJ-64179375 D mg/kg and apixaban placebo

Experimental group

Description:

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.

Treatment:

Drug: Apixaban placebo

Drug: JNJ-64179375 D mg/kg

Part 2: Group E: JNJ-64179375 placebo IV and apixaban 2.5 mg

Experimental group

Description:

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.

Treatment:

Drug: Apixaban 2.5 mg

Drug: Placebo JNJ-64179375

Trial documents