Purpose

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.

Condition

Eligibility

Eligible Ages
Over 50 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 32 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 neuropathy
  • Known previous pulmonary embolism (PE) or deep vein thrombosis (DVT) in either lower extremity

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Prevention
Masking
Single (Outcomes Assessor)
Masking Description
Treatment arms will not be blinded. But the study Drug-Doses will be blinded.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Group A: JNJ-70033093 25 mg + Placebo BID
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.
  • Drug: JNJ-70033093 25 mg
    Participants will receive JNJ-70033093 25 mg (1*25 mg capsule) BID (in Group A) or once daily (in Group E), orally for 10 to 14 postoperative days.
    Other names:
    • BMS-986177
  • Drug: Placebo
    Participants will receive placebo matching to JNJ-70033093, orally.
Experimental
Group B: JNJ-70033093 50 mg BID
Participants will receive JNJ-70033093 50 mg (2*25 mg capsules) BID orally for 10 to 14 postoperative days.
  • Drug: JNJ-70033093 50 mg
    Participants will receive JNJ-70033093 50 mg (2*25 mg capsules) BID orally for 10 to 14 postoperative days.
    Other names:
    • BMS-986177
Experimental
Group C: JNJ-70033093 100 mg + Placebo BID
Participants will receive JNJ-70033093 100 mg (1*100 mg capsule) and 1 placebo capsule BID orally for 10 to 14 postoperative days.
  • Drug: JNJ-70033093 100 mg
    Participants will receive JNJ-70033093 100 mg (1*100 mg capsule) BID, orally for 10 to 14 postoperative days.
    Other names:
    • BMS-986177
  • Drug: Placebo
    Participants will receive placebo matching to JNJ-70033093, orally.
Experimental
Group D: JNJ-70033093 200 mg BID
Participants will receive JNJ-70033093 200 mg (2*100 mg capsules) BID orally for 10 to 14 postoperative days.
  • Drug: JNJ-70033093 200 mg
    Participants will receive JNJ-70033093 200 mg (2*100 mg capsules) BID (in Group D) or once daily (in Group F), orally for 10 to 14 postoperative days.
    Other names:
    • BMS-986177
Experimental
Group E: JNJ-70033093 25 mg Once Daily + Placebo
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.
  • Drug: JNJ-70033093 25 mg
    Participants will receive JNJ-70033093 25 mg (1*25 mg capsule) BID (in Group A) or once daily (in Group E), orally for 10 to 14 postoperative days.
    Other names:
    • BMS-986177
  • Drug: Placebo
    Participants will receive placebo matching to JNJ-70033093, orally.
Experimental
Group F: JNJ-70033093 200 mg Once Daily + Placebo
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.
  • Drug: JNJ-70033093 200 mg
    Participants will receive JNJ-70033093 200 mg (2*100 mg capsules) BID (in Group D) or once daily (in Group F), orally for 10 to 14 postoperative days.
    Other names:
    • BMS-986177
  • Drug: Placebo
    Participants will receive placebo matching to JNJ-70033093, orally.
Experimental
Group G (Optional): JNJ-70033093, dose to be determined
Participants may receive JNJ-70033093 (preoperatively or once daily or a preoperatively with a BID dose), at a dose not pre-specified, to a maximum of 400-mg total daily dose.
  • Drug: JNJ-70033093, dose to be determined
    Participants may receive JNJ-70033093 (preoperatively or once daily or a preoperatively with a BID dose), at a dose not pre-specified, to a maximum of 400-mg total daily dose.
    Other names:
    • BMS-986177
Experimental
Group H (Optional): JNJ-70033093, dose to be determined
Participants may receive JNJ-70033093 (preoperatively or once daily or a preoperatively with a BID dose), at a dose not pre-specified, to a maximum of 400-mg total daily dose.
  • Drug: JNJ-70033093, dose to be determined
    Participants may receive JNJ-70033093 (preoperatively or once daily or a preoperatively with a BID dose), at a dose not pre-specified, to a maximum of 400-mg total daily dose.
    Other names:
    • BMS-986177
Active Comparator
Group I: Enoxaparin 40 mg Once Daily
Participants will receive enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days.
  • Drug: Enoxaparin 40 mg
    Participants will receive enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days.

Recruiting Locations

Memorial Hermann Memorial City Medical Center
Houston, Texas 77024

More Details

NCT ID
NCT03891524
Status
Recruiting
Sponsor
Janssen Research & Development, LLC

Study Contact

Study Contact
844-434-4210
JNJ.CT@sylogent.com

Detailed 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.