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Trial record 1 of 1 for:    NCT03251482
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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03251482
Recruitment Status : Completed
First Posted : August 16, 2017
Results First Posted : November 25, 2019
Last Update Posted : November 25, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
VTE Prophylaxis With Anticoagulation After Total Knee Replacement Surgery Drug: JNJ-64179375 0.3 mg/kg Drug: JNJ-64179375 0.6 mg/kg Drug: JNJ-64179375 1.2 mg/kg Drug: JNJ-64179375 (Dose to be Determined) Drug: JNJ-64179375 A mg/kg Drug: JNJ-64179375 B mg/kg Drug: JNJ-64179375 C mg/kg Drug: JNJ-64179375 D mg/kg Drug: Placebo JNJ-64179375 Drug: Apixaban placebo Drug: Apixaban 2.5 mg Phase 2

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 308 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double Blinded
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: 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
Actual Study Start Date : November 13, 2017
Actual Primary Completion Date : November 5, 2018
Actual Study Completion Date : November 5, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Knee Replacement
Drug Information available for: Apixaban

Arm Intervention/treatment
Experimental: 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.
Drug: JNJ-64179375 0.3 mg/kg
JNJ-64179375 0.3 milligram per kilogram (mg/kg) intravenous (IV) infusion as a single dose on Day 1.

Drug: Placebo JNJ-64179375
Matching JNJ-64179375 placebo (normal saline) administered as IV infusion as a single dose on Day 1.

Drug: Apixaban placebo
Matching apixaban placebo administered orally twice a day for 10 to 14 days.

Drug: Apixaban 2.5 mg
Apixaban 2.5 mg administered orally twice a day for 10 to 14 days.

Experimental: 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.
Drug: JNJ-64179375 0.6 mg/kg
JNJ-64179375 0.6 mg/kg IV infusion as a single dose on Day 1.

Drug: Placebo JNJ-64179375
Matching JNJ-64179375 placebo (normal saline) administered as IV infusion as a single dose on Day 1.

Drug: Apixaban placebo
Matching apixaban placebo administered orally twice a day for 10 to 14 days.

Drug: Apixaban 2.5 mg
Apixaban 2.5 mg administered orally twice a day for 10 to 14 days.

Experimental: 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.
Drug: JNJ-64179375 1.2 mg/kg
JNJ-64179375 1.2 mg/kg IV infusion as a single dose on Day 1.

Drug: Placebo JNJ-64179375
Matching JNJ-64179375 placebo (normal saline) administered as IV infusion as a single dose on Day 1.

Drug: Apixaban placebo
Matching apixaban placebo administered orally twice a day for 10 to 14 days.

Drug: Apixaban 2.5 mg
Apixaban 2.5 mg administered orally twice a day for 10 to 14 days.

Experimental: 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.
Drug: JNJ-64179375 (Dose to be Determined)
JNJ-64179375 IV infusion (Dose to be determined) as a single dose on Day 1.

Drug: Placebo JNJ-64179375
Matching JNJ-64179375 placebo (normal saline) administered as IV infusion as a single dose on Day 1.

Drug: Apixaban placebo
Matching apixaban placebo administered orally twice a day for 10 to 14 days.

Drug: Apixaban 2.5 mg
Apixaban 2.5 mg administered orally twice a day for 10 to 14 days.

Experimental: 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.
Drug: JNJ-64179375 (Dose to be Determined)
JNJ-64179375 IV infusion (Dose to be determined) as a single dose on Day 1.

Drug: Placebo JNJ-64179375
Matching JNJ-64179375 placebo (normal saline) administered as IV infusion as a single dose on Day 1.

Drug: Apixaban placebo
Matching apixaban placebo administered orally twice a day for 10 to 14 days.

Drug: Apixaban 2.5 mg
Apixaban 2.5 mg administered orally twice a day for 10 to 14 days.

Experimental: 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.
Drug: JNJ-64179375 (Dose to be Determined)
JNJ-64179375 IV infusion (Dose to be determined) as a single dose on Day 1.

Drug: Placebo JNJ-64179375
Matching JNJ-64179375 placebo (normal saline) administered as IV infusion as a single dose on Day 1.

Drug: Apixaban placebo
Matching apixaban placebo administered orally twice a day for 10 to 14 days.

Drug: Apixaban 2.5 mg
Apixaban 2.5 mg administered orally twice a day for 10 to 14 days.

Experimental: 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.
Drug: JNJ-64179375 A mg/kg
JNJ-64179375 Dose A mg/kg IV as a single dose on Day 1.

Drug: Apixaban placebo
Matching apixaban placebo administered orally twice a day for 10 to 14 days.

Experimental: 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.
Drug: JNJ-64179375 B mg/kg
JNJ-64179375 Dose B mg/kg IV as a single dose on Day 1.

Drug: Apixaban placebo
Matching apixaban placebo administered orally twice a day for 10 to 14 days.

Experimental: 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.
Drug: JNJ-64179375 C mg/kg
JNJ-64179375 Dose C mg/kg IV as a single dose on Day 1.

Drug: Apixaban placebo
Matching apixaban placebo administered orally twice a day for 10 to 14 days.

Experimental: 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.
Drug: JNJ-64179375 D mg/kg
JNJ-64179375 Dose D mg/kg IV as a single dose on Day 1.

Drug: Apixaban placebo
Matching apixaban placebo administered orally twice a day for 10 to 14 days.

Experimental: 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.
Drug: Placebo JNJ-64179375
Matching JNJ-64179375 placebo (normal saline) administered as IV infusion as a single dose on Day 1.

Drug: Apixaban 2.5 mg
Apixaban 2.5 mg administered orally twice a day for 10 to 14 days.




Primary Outcome Measures :
  1. Number of Participants With Treatment-emergent Bleeding Events (Clinical Events Committee [CEC]- Adjudicated) [ Time Frame: 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.

  2. Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated) [ Time Frame: 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.


Secondary Outcome Measures :
  1. Number of Participants With Composite of Major and CRNM Bleeding Events (CEC-adjudicated) [ Time Frame: Up to Day 10 to 14 (visit observation period) ]
    Number of participants with composite of major and CRNM bleeding events (adjudicated by CEC) were reported. Major Bleeding: Fatal bleeding; Bleeding that is symptomatic and occurs in critical area/organ and/or; Extrasurgical site bleeding causing fall in Hb level of 20 g/L or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; Surgical site bleeding that requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; Surgical site bleeding that is unexpected and prolonged and/or sufficiently large to cause hemodynamic instability. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE and meets at least 1 of following criteria: Epistaxis, Gastrointestinal bleed, Hematuria, Bruising/ecchymosis, Hemoptysis, Hematoma.

  2. Number of Participants With Major Bleeding Event (CEC-adjudicated) [ Time Frame: Up to Day 10 to 14 (visit observation period) ]
    Number of participants with major bleeding events (BE) (adjudicated by CEC) were reported. Major Bleeding: Fatal bleeding; Bleeding that is symptomatic and occurs in critical area/organ and/or; Extrasurgical site bleeding causing fall in hemoglobin (Hb) level of 20 grams per liter (g/L) or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; Surgical site bleeding that requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; Surgical site bleeding that is unexpected and prolonged and/or sufficiently large to cause hemodynamic instability.

  3. Number of Participants With Clinically Relevant Non-major (CRNM) Bleeding Events (CEC-adjudicated) [ Time Frame: Up to Day 10 to 14 (visit observation period) ]
    Number of participants with CRNM bleeding events (adjudicated by CEC) were reported. CRNM bleeding was defined as acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major bleeding event and meets at least 1 of following criteria: Epistaxis, Gastrointestinal bleed, Hematuria, Bruising/ecchymosis, Hemoptysis, Hematoma.

  4. Number of Participants With Major Bleeding or CRNM Bleeding Events (CEC-adjudicated) [ Time Frame: Up to Day 10 and 14 (visit observation period) ]
    Number of participants with major bleeding or CRNM bleeding events (adjudicated by CEC) were reported. Major Bleeding: Fatal bleeding; Bleeding that is symptomatic and occurs in critical area/organ and/or; Extrasurgical site bleeding causing fall in Hb level of 20 g/L or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; Surgical site bleeding that requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; Surgical site bleeding that is unexpected and prolonged and/or sufficiently large to cause hemodynamic instability. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE and meets at least 1 of following criteria: Epistaxis, Gastrointestinal bleed, Hematuria, Bruising/ecchymosis, Hemoptysis, Hematoma.

  5. Number of Participants With Minimal Bleeding Events (CEC-adjudicated) [ Time Frame: Up to Day 10 to 14 (visit observation period) ]
    Number of participants with minimal bleeding events (adjudicated by CEC) were reported. Minimal bleeding event was defined as any bleeding event not met major or CRNM criteria.

  6. Number of Participants With Major VTE (CEC-adjudicated) [ Time Frame: Up to Day 10 to 14 (visit observation period) ]
    Number of participants with major VTE (adjudicated by CEC) were reported. Major VTE was defined as a composite of proximal DVT (asymptomatic confirmed by venography or objectively confirmed symptomatic), nonfatal PE, or any death. 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.

  7. Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) [ Time Frame: Up to Day 10 to 14 (visit observation period) ]
    Number of participants with proximal DVT (adjudicated by CEC) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic. 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.

  8. Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) [ Time Frame: Up to Day 10 to 14 (visit observation period) ]
    Number of participants with nonfatal PE (adjudicated by CEC) were reported.

  9. Number of Participants With Death (CEC-adjudicated) [ Time Frame: Up to Day 10 to 14 (visit observation period) ]
    Number of participants with death (adjudicated by CEC) were reported.

  10. Number of Participants With Proximal and Distal DVT (CEC-adjudicated) [ Time Frame: Up to Day 10 to 14 (visit observation period) ]
    Number of participants with proximal and distal DVT (adjudicated by CEC) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic. 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.

  11. Number of Participants With Distal DVT (CEC-adjudicated) [ Time Frame: Up to Day 10 to 14 (visit observation period) ]
    Number of participants with distal DVT (adjudicated by CEC) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03251482


Locations
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Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research Development, LLC Clinical Trial Janssen Research & Development, LLC
  Study Documents (Full-Text)

Documents provided by Janssen Research & Development, LLC:
Study Protocol  [PDF] September 11, 2017
Statistical Analysis Plan  [PDF] October 18, 2017

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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03251482    
Other Study ID Numbers: CR108344
2016-004550-15 ( EudraCT Number )
64179375THR2001 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: August 16, 2017    Key Record Dates
Results First Posted: November 25, 2019
Last Update Posted: November 25, 2019
Last Verified: November 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Apixaban
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants