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A Trial to Learn How Well REGN9933 Works for Preventing Blood Clots After Knee Replacement Surgery in Adult Participants

Primary Purpose

Venous Thromboembolism

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
REGN9933
Enoxaparin
Apixiban
Sponsored by
Regeneron Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Venous Thromboembolism focused on measuring Anti-factor XI (FXI) monoclonal antibody, Deep Vein Thrombosis, Unilateral total knee arthroplasty (TKA),

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria: Undergoing elective unilateral TKA Has a body weight ≤130 kg at screening visit Is judged by the investigator to be in good health based on medical history, physical examination, vital sign measurements, and Electrocardiograms (ECG) performed at screening and/or prior to administration of initial dose of study drug Is in good health based on laboratory safety testing obtained during the screening period as described in the protocol Key Exclusion Criteria: History of bleeding in the past 6 months requiring hospitalization or transfusion; history of intracranial or intraocular bleeding, excessive operative or post-operative bleeding, and traumatic spinal or epidural anesthesia; history of bleeding diathesis. History of thromboembolic disease or thrombophilia History of major surgery, including brain, spinal, or ocular, within approximately the past 6 months. History of major trauma within approximately the past 6 months. Hospitalized (>24 hours) for any reason within 30 days of the screening visit Using the Modification of Diet in Renal Disease equation, has an estimated glomerular filtration rate as described in the protocol Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Sites / Locations

  • Ziekenhuis Oost-Limburg- Campus Sint-Jan
  • MBAL Heart and Brain Hospital
  • UMHAT St. Georgi EAD
  • Durham Bone and Joint Specialists
  • Hamilton Health Sciences, Juravinski Hospital
  • MAV Korhaz es Rendelointezet Szolnok
  • Budai Irgalmasrendi Korhaz
  • Department of Orthopedics, Somogy County Mór Kaposi Teaching Hospital
  • Rambam Health Care Campus - Internal Medicine
  • Meir Medical Center
  • Beilinson Medical Center
  • Liepaja Regional Hospital
  • Vidzemes HospitalRecruiting
  • Riga's 2nd HospitalRecruiting
  • Hospital of Traumatology and OrthopaedicsRecruiting
  • Lietuvos Sveikatos Mokslu Universiteto Ligonine Kauno KlinikRecruiting
  • Klaipeda University HospitalRecruiting
  • Lietuvos Sveikatos Mokslu Universiteto Kauno LigoninėRecruiting
  • Specjalistyczny Szpital im. E. Szczeklika w TarnowieRecruiting
  • SP ZOZ Centralny Szpital Kliniczny UM w Lodzi
  • Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie
  • Samodzielny Publiczny Zaklad Opieki Zdrowotnej w Radzyniu PodlaskimRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

REGN9933

Enoxaparin

Apixaban

Arm Description

REGN9933 will be administered by intravenous (IV) infusion

Enoxaparin will be administered by subcutaneous (SC) administration

Apixaban will be administered orally twice a day

Outcomes

Primary Outcome Measures

Incidence of confirmed, adjudicated venous thromboembolism (VTE)
Asymptomatic deep DVT detected by unilateral venography of the operated leg; confirmed symptomatic DVT of either leg; confirmed fatal or nonfatal pulmonary embolism (PE) including unexplained death for which PE cannot be ruled out (REGN9933 vs enoxaparin)

Secondary Outcome Measures

Incidence of major bleeding
International Society on Thrombosis and Hemostasis (ISTH) criteria for Major Bleeding as described in the protocol
Incidence of clinically relevant non-major (CRNM) bleeding
International Society on Thrombosis and Hemostasis (ISTH) criteria for Clinically Relevant Non-Major Bleeding as described in the protocol
Incidence of treatment emergent adverse events (TEAEs)
A TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment
Incidence of major VTE
Major VTE is defined as: proximal DVT; confirmed symptomatic DVT of either leg; confirmed fatal or nonfatal PE including unexplained death for which PE cannot be ruled out
Incidence of DVT
DVT will be measured by venography of the operated leg
Concentrations of REGN9933 in serum
The concentrations of REGN9933 over time will be summarized by descriptive statistics by study arm for the overall population
Change in activated partial thromboplastin time (aPTT)
aPTT will be used to measure the anticipated anticoagulant effect of REGN9933
Change in prothrombin time (PT)
PT is a measure of extrinsic and/or common pathway function.
Incidence of anti-drug antibodies (ADA) to REGN9933
Immunogenicity will be characterized per drug molecule by ADA status
Titer of anti-drug antibodies to REGN9933
Immunogenicity will be characterized per drug molecule by ADA status.
Incidence of confirmed, adjudicated VTE
Asymptomatic deep DVT detected by unilateral venography of the operated leg; confirmed symptomatic DVT of either leg; confirmed fatal or nonfatal pulmonary embolism (PE) including unexplained death for which PE cannot be ruled out (enoxaparin vs apixaban)

Full Information

First Posted
November 8, 2022
Last Updated
October 11, 2023
Sponsor
Regeneron Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT05618808
Brief Title
A Trial to Learn How Well REGN9933 Works for Preventing Blood Clots After Knee Replacement Surgery in Adult Participants
Official Title
A Phase 2, Multicenter, Randomized, Open-Label, Active-Control Study of REGN9933, a Factor XI Monoclonal Antibody, for Prevention of Venous Thromboembolism After Elective, Unilateral, Total Knee Arthroplasty
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 24, 2023 (Actual)
Primary Completion Date
August 10, 2024 (Anticipated)
Study Completion Date
August 10, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary objective of the study is to evaluate the efficacy of REGN9933 for the prevention of venous thromboembolism (VTE) after unilateral total knee arthroplasty (TKA), compared to enoxaparin The secondary objectives of the study are: To evaluate the bleeding risk (ie, major and clinically relevant non-major [CRNM] bleeding) of REGN9933 after unilateral TKA through time of venography, compared to enoxaparin To assess overall safety and tolerability of REGN9933 in participants undergoing TKA To evaluate the efficacy of REGN9933 in prevention of clinically relevant VTE, compared to enoxaparin To evaluate the efficacy of REGN9933 in prevention of deep venous thrombosis (DVT) detected by venography, compared to enoxaparin To evaluate the pharmacokinetics (PK) of REGN9933 after single intravenous (IV) administration To assess pharmacodynamic (PD) effects of REGN9933 on intrinsic and extrinsic coagulation pathways To assess immunogenicity following a single dose of REGN9933 over time To compare the efficacy of enoxaparin and apixaban in prevention of VTE after unilateral TKA

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Venous Thromboembolism
Keywords
Anti-factor XI (FXI) monoclonal antibody, Deep Vein Thrombosis, Unilateral total knee arthroplasty (TKA),

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
360 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
REGN9933
Arm Type
Experimental
Arm Description
REGN9933 will be administered by intravenous (IV) infusion
Arm Title
Enoxaparin
Arm Type
Active Comparator
Arm Description
Enoxaparin will be administered by subcutaneous (SC) administration
Arm Title
Apixaban
Arm Type
Active Comparator
Arm Description
Apixaban will be administered orally twice a day
Intervention Type
Drug
Intervention Name(s)
REGN9933
Intervention Description
Participants will receive a single dose of REGN9933 by IV infusion
Intervention Type
Drug
Intervention Name(s)
Enoxaparin
Other Intervention Name(s)
Lovenox
Intervention Description
Participants will receive enoxaparin by SC administration daily through the time of venography (or day 12, whichever is earlier)
Intervention Type
Drug
Intervention Name(s)
Apixiban
Other Intervention Name(s)
Eliquis
Intervention Description
Participants will receive apixaban orally twice a day through the time of venography (or day 12, whichever is earlier)
Primary Outcome Measure Information:
Title
Incidence of confirmed, adjudicated venous thromboembolism (VTE)
Description
Asymptomatic deep DVT detected by unilateral venography of the operated leg; confirmed symptomatic DVT of either leg; confirmed fatal or nonfatal pulmonary embolism (PE) including unexplained death for which PE cannot be ruled out (REGN9933 vs enoxaparin)
Time Frame
Through Day 12
Secondary Outcome Measure Information:
Title
Incidence of major bleeding
Description
International Society on Thrombosis and Hemostasis (ISTH) criteria for Major Bleeding as described in the protocol
Time Frame
Up to approximately Day 12
Title
Incidence of clinically relevant non-major (CRNM) bleeding
Description
International Society on Thrombosis and Hemostasis (ISTH) criteria for Clinically Relevant Non-Major Bleeding as described in the protocol
Time Frame
Up to approximately Day 12
Title
Incidence of treatment emergent adverse events (TEAEs)
Description
A TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment
Time Frame
Through end of study; approximately Day 75
Title
Incidence of major VTE
Description
Major VTE is defined as: proximal DVT; confirmed symptomatic DVT of either leg; confirmed fatal or nonfatal PE including unexplained death for which PE cannot be ruled out
Time Frame
Through Day 12
Title
Incidence of DVT
Description
DVT will be measured by venography of the operated leg
Time Frame
Approximately Day 12
Title
Concentrations of REGN9933 in serum
Description
The concentrations of REGN9933 over time will be summarized by descriptive statistics by study arm for the overall population
Time Frame
Through end of study; approximately Day 75
Title
Change in activated partial thromboplastin time (aPTT)
Description
aPTT will be used to measure the anticipated anticoagulant effect of REGN9933
Time Frame
Baseline to end of study; approximately Day 75
Title
Change in prothrombin time (PT)
Description
PT is a measure of extrinsic and/or common pathway function.
Time Frame
Baseline to end of study; approximately Day 75
Title
Incidence of anti-drug antibodies (ADA) to REGN9933
Description
Immunogenicity will be characterized per drug molecule by ADA status
Time Frame
Through end of study; approximately Day 75
Title
Titer of anti-drug antibodies to REGN9933
Description
Immunogenicity will be characterized per drug molecule by ADA status.
Time Frame
Through end of study; approximately Day 75
Title
Incidence of confirmed, adjudicated VTE
Description
Asymptomatic deep DVT detected by unilateral venography of the operated leg; confirmed symptomatic DVT of either leg; confirmed fatal or nonfatal pulmonary embolism (PE) including unexplained death for which PE cannot be ruled out (enoxaparin vs apixaban)
Time Frame
Baseline through Day 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Undergoing elective unilateral TKA Has a body weight ≤130 kg at screening visit Is judged by the investigator to be in good health based on medical history, physical examination, vital sign measurements, and Electrocardiograms (ECG) performed at screening and/or prior to administration of initial dose of study drug Is in good health based on laboratory safety testing obtained during the screening period as described in the protocol Key Exclusion Criteria: History of bleeding in the past 6 months requiring hospitalization or transfusion; history of intracranial or intraocular bleeding, excessive operative or post-operative bleeding, and traumatic spinal or epidural anesthesia; history of bleeding diathesis. History of thromboembolic disease or thrombophilia History of major surgery, including brain, spinal, or ocular, within approximately the past 6 months. History of major trauma within approximately the past 6 months. Hospitalized (>24 hours) for any reason within 30 days of the screening visit Using the Modification of Diet in Renal Disease equation, has an estimated glomerular filtration rate as described in the protocol Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Trials Administrator
Phone
844-734-6643
Email
clinicaltrials@regeneron.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Ziekenhuis Oost-Limburg- Campus Sint-Jan
City
Genk
State/Province
Limburg
ZIP/Postal Code
3600
Country
Belgium
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Richard Witvrouw
First Name & Middle Initial & Last Name & Degree
Richard Witvrouw
Facility Name
MBAL Heart and Brain Hospital
City
Pleven
ZIP/Postal Code
5800
Country
Bulgaria
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Georgi Dimitrov
First Name & Middle Initial & Last Name & Degree
Georgi Dimitrov
Facility Name
UMHAT St. Georgi EAD
City
Plovdiv
ZIP/Postal Code
4002
Country
Bulgaria
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vladmir Stavrev
First Name & Middle Initial & Last Name & Degree
Vladmir Stavrev
Facility Name
Durham Bone and Joint Specialists
City
Ajax
State/Province
Ontario
ZIP/Postal Code
L1S 7K7
Country
Canada
Individual Site Status
Suspended
Facility Name
Hamilton Health Sciences, Juravinski Hospital
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 1C3
Country
Canada
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Gross
First Name & Middle Initial & Last Name & Degree
Peter Gross
Facility Name
MAV Korhaz es Rendelointezet Szolnok
City
Szolnok
State/Province
Jász-Nagykun-Szolnok
ZIP/Postal Code
5000
Country
Hungary
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laszlo Samson
First Name & Middle Initial & Last Name & Degree
Laszlo Samson
Facility Name
Budai Irgalmasrendi Korhaz
City
Budapest
ZIP/Postal Code
1027
Country
Hungary
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gabor Janositz
First Name & Middle Initial & Last Name & Degree
Gabor Janositz
Facility Name
Department of Orthopedics, Somogy County Mór Kaposi Teaching Hospital
City
Kaposvar
ZIP/Postal Code
7400
Country
Hungary
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
István Szabo
First Name & Middle Initial & Last Name & Degree
István Szabo
Facility Name
Rambam Health Care Campus - Internal Medicine
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Doron Norman
First Name & Middle Initial & Last Name & Degree
Doron Norman
Facility Name
Meir Medical Center
City
Kfar-Saba
ZIP/Postal Code
44281
Country
Israel
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yaron Brin
First Name & Middle Initial & Last Name & Degree
Yaron Brin
Facility Name
Beilinson Medical Center
City
Petach Tikva
ZIP/Postal Code
4941492
Country
Israel
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yona Kosashvili
First Name & Middle Initial & Last Name & Degree
Yona Kosashvili
Facility Name
Liepaja Regional Hospital
City
Liepaja
ZIP/Postal Code
LV3414
Country
Latvia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Uldis Argalis
First Name & Middle Initial & Last Name & Degree
Uldis Argalis
Facility Name
Vidzemes Hospital
City
Riga
ZIP/Postal Code
LV-1002
Country
Latvia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aivars Baurovskis
First Name & Middle Initial & Last Name & Degree
Aivars Baurovskis
Facility Name
Riga's 2nd Hospital
City
Riga
ZIP/Postal Code
LV-1004
Country
Latvia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sandris Petronis
First Name & Middle Initial & Last Name & Degree
Sandris Petronis
Facility Name
Hospital of Traumatology and Orthopaedics
City
Riga
ZIP/Postal Code
LV1005
Country
Latvia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maris Zambrans
First Name & Middle Initial & Last Name & Degree
Maris Zambrans
Facility Name
Lietuvos Sveikatos Mokslu Universiteto Ligonine Kauno Klinik
City
Kaunas
State/Province
Kauno Apskritis
ZIP/Postal Code
LT-50009
Country
Lithuania
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alfredas Smailys
First Name & Middle Initial & Last Name & Degree
Alfredas Smailys
Facility Name
Klaipeda University Hospital
City
Klaipeda
State/Province
Klaipedos Apskritis
ZIP/Postal Code
LT-92288
Country
Lithuania
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Algimantas Cebatorius
First Name & Middle Initial & Last Name & Degree
Algimantas Cebatorius
Facility Name
Lietuvos Sveikatos Mokslu Universiteto Kauno Ligoninė
City
Kaunas
ZIP/Postal Code
LT-44320
Country
Lithuania
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juozas Belickas
First Name & Middle Initial & Last Name & Degree
Juozas Belickas
Facility Name
Specjalistyczny Szpital im. E. Szczeklika w Tarnowie
City
Tarnow
State/Province
Malopolskie
ZIP/Postal Code
33-100
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Grzegorz Sterkowicz
First Name & Middle Initial & Last Name & Degree
Grzegorz Sterkowicz
Facility Name
SP ZOZ Centralny Szpital Kliniczny UM w Lodzi
City
Lodz
ZIP/Postal Code
90-153
Country
Poland
Individual Site Status
Suspended
Facility Name
Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie
City
Lublin
ZIP/Postal Code
20-954
Country
Poland
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tomasz Blicharski
First Name & Middle Initial & Last Name & Degree
Tomasz Blicharski
Facility Name
Samodzielny Publiczny Zaklad Opieki Zdrowotnej w Radzyniu Podlaskim
City
Radzyn Podlaski
ZIP/Postal Code
21-300
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Weglowski
First Name & Middle Initial & Last Name & Degree
Robert Weglowski

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
IPD Sharing Time Frame
When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
IPD Sharing Access Criteria
Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
IPD Sharing URL
https://vivli.org/

Learn more about this trial

A Trial to Learn How Well REGN9933 Works for Preventing Blood Clots After Knee Replacement Surgery in Adult Participants

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