A 2-Part Study to Evaluate the Safety and Efficacy of Intravenous JNJ-64179375 Versus Oral Apixaban in Subjects Undergoing Elective Total Knee Replacement

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2016-004550-15-ES
• Date of registration: 31/07/2017
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: A 2-Part Study to Evaluate the Safety and Efficacy of Intravenous JNJ-64179375 Versus Oral Apixaban in Subjects Undergoing Elective Total Knee Replacement
• Scientific 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
• Date of first enrolment: 25/10/2017
• Target sample size: 1500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004550-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 11
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Belgium, Brazil, Bulgaria, Canada, Czech Republic, Greece, Hungary, Japan, Latvia, Lithuania, Malaysia, Poland, Portugal, Romania, Russian Federation, Spain, Sweden, Turkey, Ukraine, United States

Contacts

• Name: Global Clinical Operations Spain
• Affiliation: Janssen Cilag, S.A.

• Name: Global Clinical Operations Spain
• Affiliation: Janssen Cilag, S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
- Male or female of non-childbearing potential
- At least 50 years of age or older
- Weight 40 kg to 150 kg
- Medically appropriate for postoperative anticoagulant prophylaxis
- Has undergone an elective primary unilateral TKR
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1000
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 500

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 DVT in either lower extremity
- Any preplanned invasive procedure (eg, surgery, colonoscopy) up to Week 18 for which anticoagulant or antiplatelet therapy would be interrupted
- Planned use of intermittent pneumatic compression after randomization


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Thromboembolism in subjects who have undergone an elective primary unilateral total knee replacement

Intervention(s)

Product Name: JNJ-64179375
Product Code: JNJ-64179375
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not applicable
Current Sponsor code: JNJ-64179375
Other descriptive name: JNJ-64179375
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for injection/infusion
Route of administration of the placebo: Intravenous use

Trade Name: Eliquis
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: APIXABAN
CAS Number: 503612-47-3
Current Sponsor code: 80000-G-109
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: Part 1 :
• to assess the dose response of JNJ-64179375 for the occurrence of the composite endpoint of any bleeding events, the composite endpoint of major or clinically relevant nonmajor bleeding events, and the individual components of the composite endpoint of any bleeding event
• to assess the dose response of JNJ-64179375 for the prevention of total VTE and the individual components of total VTE
Part 2:
• to assess the dose response of JNJ-64179375 for the occurrence of the composite endpoint of any bleeding events, the composite endpoint of major or clinically relevant nonmajor bleeding events, and the individual components of the composite endpoint of any bleeding event
• to assess the dose response of JNJ-64179375 for the prevention of major VTE and the individual components of the total VTE endpoint

Please refer to the protocol for further secondary objectives common to both Part 1 and Part 2

Primary end point(s): The endpoints of the study will be the same for Parts 1 and 2 although the focus of Part 1 will be primarily dose escalation based on safety while the focus of Part 2 will primarily be the assessment of dose response in both safety and efficacy.

Common Endpoints in Parts 1 and 2

Primary Safety Endpoint
The primary safety endpoint is any bleeding event defined as the composite of major, clinically relevant nonmajor, and minimal bleeding events assessed through the Day 10-14 visit.

Primary Efficacy Endpoint
The primary efficacy endpoint is total VTE, defined as the composite of proximal and/or distal DVT (asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic), nonfatal PE, or any death assessed through the Day 10-14 visit.

Timepoint(s) of evaluation of this end point: Through the Day 10-14 visit.

Main Objective: Part 1: The primary objective is to assess the safety and tolerability of JNJ-64179375 for each dose level for dose escalation within Part 1 and any bleeding events (the composite of major, clinically relevant nonmajor, and minimal bleeding events) for the selection of doses for Part 2.

Part 2: The primary objective 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 PE, or any death).

Secondary Outcome(s)

Secondary end point(s): Key Secondary Endpoints
The key secondary endpoints are the assessment of the primary endpoints through the Week 18 visit, and:
• All individual components of the primary safety endpoint (major bleeding, clinically relevant nonmajor bleeding, and minimal bleeding)
• Composite of major and clinically relevant nonmajor bleeding
• Major VTE, a composite of proximal DVT (asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic), nonfatal PE, or any death
• All individual components of the primary efficacy endpoint (ie, proximal and/or distal DVT [asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic], nonfatal PE, any death)
Other Secondary Endpoints
• Any wound or joint complication in the operated leg

Timepoint(s) of evaluation of this end point: Through the Week 18 visit.

Secondary ID(s)

64179375THR2001

2016-004550-15-BE

Source(s) of Monetary Support

Janssen Research & Development, LLC

Ethics review

Status: Approved
Approval date:
Contact: