Clinical trial NCT05618808: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Venous Thromboembolism
Keywords: Anti-factor XI (FXI) monoclonal antibody
Deep Vein Thrombosis
Unilateral total knee arthroplasty (TKA),
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-11-16
Enrollment: 373
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Key Inclusion Criteria:

1. Undergoing elective unilateral TKA
2. Has a body weight ≤130 kg at screening visit
3. 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
4. Is in good health based on laboratory safety testing obtained during the screening period as described in the protocol

Key Exclusion Criteria:

1. 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.
2. History of thromboembolic disease or thrombophilia
3. History of major surgery, including brain, spinal, or ocular, within approximately the past 6 months.
4. History of major trauma within approximately the past 6 months.
5. Hospitalized (\>24 hours) for any reason within 30 days of the screening visit
6. 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

Primary outcomes:
measure: Incidence of confirmed, adjudicated venous thromboembolism (VTE)
timeFrame: Through Day 12
Secondary outcomes:
measure: Incidence of major bleeding
timeFrame: Up to approximately Day 12
measure: Incidence of clinically relevant non-major (CRNM) bleeding
timeFrame: Up to approximately Day 12
measure: Incidence of treatment emergent adverse events (TEAEs)
timeFrame: Through end of study; approximately Day 75
measure: Incidence of major VTE
timeFrame: Through Day 12
measure: Incidence of DVT
timeFrame: Approximately Day 12
measure: Concentrations of REGN9933 in serum
timeFrame: Through end of study; approximately Day 75
measure: Change in activated partial thromboplastin time (aPTT)
timeFrame: Baseline to end of study; approximately Day 75
measure: Change in prothrombin time (PT)
timeFrame: Baseline to end of study; approximately Day 75
measure: Incidence of anti-drug antibodies (ADA) to REGN9933
timeFrame: Through end of study; approximately Day 75
measure: Titer of anti-drug antibodies to REGN9933
timeFrame: Through end of study; approximately Day 75
measure: Incidence of confirmed, adjudicated VTE
timeFrame: Baseline through Day 12
Other outcomes:
Locations:
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg- Campus Sint-Jan
state: Limburg
city: Pleven
country: Bulgaria
facility: MBAL Heart and Brain Hospital
city: Ajax
country: Canada
facility: Durham Bone and Joint Specialists
state: Ontario
city: Szolnok
country: Hungary
facility: MAV Korhaz es Rendelointezet Szolnok
state: Jász-Nagykun-Szolnok
city: Kaposvar
country: Hungary
facility: Department of Orthopedics, Somogy County Mór Kaposi Teaching Hospital
city: Liepaja
country: Latvia
facility: Liepaja Regional Hospital
city: Riga
country: Latvia
facility: Vidzemes Hospital
city: Riga
country: Latvia
facility: Riga's 2nd Hospital
city: Riga
country: Latvia
facility: Hospital of Traumatology and Orthopaedics
city: Kaunas
country: Lithuania
facility: Lietuvos Sveikatos Mokslu Universiteto Ligonine Kauno Klinik
state: Kauno Apskritis
city: Klaipeda
country: Lithuania
facility: Klaipeda University Hospital
state: Klaipedos Apskritis
city: Kaunas
country: Lithuania
facility: Lietuvos Sveikatos Mokslu Universiteto Kauno Ligoninė
city: Tarnow
country: Poland
facility: Specjalistyczny Szpital im. E. Szczeklika w Tarnowie
state: Malopolskie
city: Lodz
country: Poland
facility: SP ZOZ Centralny Szpital Kliniczny UM w Lodzi
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie
city: Radzyn Podlaski
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej w Radzyniu Podlaskim
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: