A Study of JNJ-70033093 (BMS-986177) Versus Subcutaneous Enoxaparin in Participants Undergoing Elective Total Knee Replacement Surgery (AXIOMATIC-TKR)

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 2

Conditions: Arthroplasty, Replacement, Knee

Treatments: Drug: Enoxaparin 40 mg; Drug: Placebo; Drug: JNJ-70033093 100 mg; Drug: JNJ-70033093 25 mg; Drug: JNJ-70033093 200 mg; Drug: JNJ-70033093 50 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT03891524

70033093THR2001 (Other Identifier)

CR108600

2018-004237-32 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to determine the efficacy of JNJ-70033093 in preventing total venous thromboembolism (VTE) events (proximal and/or distal deep vein thrombosis [DVT] [asymptomatic confirmed by venography assessment or objectively confirmed symptomatic], nonfatal pulmonary embolism [PE], or any death) during the treatment period.

Full description

JNJ-70033093 is an oral anticoagulant for prevention and treatment of thromboembolic events (for example, VTE) that binds and inhibits activated form of human coagulation Factor XI (FXIa) with high affinity and selectivity. The study will consist of 3 phases: up to 30-day screening phase before total knee replacement (TKR) surgery, 10 to14 day postoperative dosing phase, and 4-week follow-up phase. The hypothesis of this study is JNJ-70033093 reduces risk of total VTE during treatment period. The total duration of participation following randomization will be approximately 6 weeks. Efficacy evaluations include unilateral venography assessment of operated leg and assessments of symptomatic DVT, PE, or death. Safety evaluation includes adverse events, clinical laboratory tests, and physical examinations. The safety and efficacy will be monitored throughout the study.

Enrollment: 1,242 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Medically stable and appropriate for anticoagulant prophylaxis as determined by the investigator on the basis of physical examination, medical history, and vital signs performed as part of screening for elective total knee replacement (TKR) surgery
• Medically stable and appropriate for anticoagulant prophylaxis on the basis of clinical laboratory tests performed as part of local standard-of-care as part of screening for elective TKR surgery
• Has plans to undergo an elective primary unilateral TKR surgery
• A woman must be- a) Not of childbearing potential; b) Of childbearing potential and practicing a highly effective method of contraception (failure rate of less than [<]1 percent [%] per year when used consistently and correctly) and agrees to remain on a highly effective method for the duration of study drug with JNJ-70033093 plus 5 half-lives of study drug plus 30 days (duration of ovulatory cycle) for a total of 34 days after the completion of treatment, pregnancy testing (serum or urine) prior to the first dose of study drug
• Willing and able to adhere to the lifestyle restrictions specified in this protocol

Exclusion criteria

• History of any condition for which the use of low molecular-weight heparin (LMWH) is not recommended in the opinion of the investigator (for example, previous allergic reaction, creatinine clearance <30 milliliter per minute [mL/minute])
• History of severe hepatic impairment
• Planned bilateral revision or unicompartmental procedure
• Unable to undergo venography (for example, due to contrast agent allergy, poor venous access, or impaired renal function that would increase the risk of contrast-induced nephropathy
• Known previous pulmonary embolism (PE) or deep vein thrombosis (DVT) in either lower extremity

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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1,242 participants in 8 patient groups

Group A: JNJ-70033093 25 mg + Placebo BID

Experimental group

Description:

Participants will receive JNJ-70033093 25 milligram (mg) (1\*25 mg capsule) and 1 placebo capsule twice daily (BID), orally for 10 to 14 postoperative days.

Treatment:

Drug: JNJ-70033093 25 mg

Drug: Placebo

Group B: JNJ-70033093 50 mg BID

Experimental group

Description:

Participants will receive JNJ-70033093 50 mg (2\*25 mg capsules) BID orally for 10 to 14 postoperative days.

Treatment:

Drug: JNJ-70033093 50 mg

Group C: JNJ-70033093 100 mg + Placebo BID

Experimental group

Description:

Participants will receive JNJ-70033093 100 mg (1\*100 mg capsule) and 1 placebo capsule BID orally for 10 to 14 postoperative days.

Treatment:

Drug: JNJ-70033093 100 mg

Drug: Placebo

Group D: JNJ-70033093 200 mg BID

Experimental group

Description:

Participants will receive JNJ-70033093 200 mg (2\*100 mg capsules) BID orally for 10 to 14 postoperative days.

Treatment:

Drug: JNJ-70033093 200 mg

Group E: JNJ-70033093 25 mg Once Daily + Placebo

Experimental group

Description:

Participants will receive JNJ-70033093 25 mg (1\*25 mg capsule) once daily and 1 placebo capsule in the morning and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.

Treatment:

Drug: JNJ-70033093 25 mg

Drug: Placebo

Group F: JNJ-70033093 200 mg Once Daily + Placebo

Experimental group

Description:

Participants will receive JNJ-70033093 200 mg (2\*100 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.

Treatment:

Drug: JNJ-70033093 200 mg

Drug: Placebo

Group G: JNJ-70033093 50 mg once daily + Placebo

Experimental group

Description:

Participants will receive JNJ-70033093 50 mg (2\*25 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.

Treatment:

Drug: JNJ-70033093 50 mg

Drug: Placebo

Group I: Enoxaparin 40 mg Once Daily

Active Comparator group

Description:

Participants will receive enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days.

Treatment:

Drug: Enoxaparin 40 mg