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

Venous Thromboembolism Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05618808
• Other study ID #: R9933-DVT-2230
• Secondary ID: 2022-501470-18-0
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 24, 2023
• Est. completion date: May 29, 2024

Study information

• Verified date: March 2024
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 373
• Est. completion date: May 29, 2024
• Est. primary completion date: May 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Thromboembolism
• Venous Thromboembolism

Intervention

Drug:
• REGN9933
Participants will receive a single dose of REGN9933 by IV infusion
• Enoxaparin
Participants will receive enoxaparin by SC administration daily through the time of venography (or day 12, whichever is earlier)
• Apixiban
Participants will receive apixaban orally twice a day through the time of venography (or day 12, whichever is earlier)

Locations

Country	Name	City	State
Belgium	Ziekenhuis Oost-Limburg- Campus Sint-Jan	Genk	Limburg
Bulgaria	MBAL Heart and Brain Hospital	Pleven
Canada	Durham Bone and Joint Specialists	Ajax	Ontario
Hungary	Department of Orthopedics, Somogy County Mór Kaposi Teaching Hospital	Kaposvar
Hungary	MAV Korhaz es Rendelointezet Szolnok	Szolnok	Jász-Nagykun-Szolnok
Latvia	Liepaja Regional Hospital	Liepaja
Latvia	Hospital of Traumatology and Orthopaedics	Riga
Latvia	Riga's 2nd Hospital	Riga
Latvia	Vidzemes Hospital	Riga
Lithuania	Lietuvos Sveikatos Mokslu Universiteto Kauno Ligonine	Kaunas
Lithuania	Lietuvos Sveikatos Mokslu Universiteto Ligonine Kauno Klinik	Kaunas	Kauno Apskritis
Lithuania	Klaipeda University Hospital	Klaipeda	Klaipedos Apskritis
Poland	SP ZOZ Centralny Szpital Kliniczny UM w Lodzi	Lodz
Poland	Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie	Lublin
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej w Radzyniu Podlaskim	Radzyn Podlaski
Poland	Specjalistyczny Szpital im. E. Szczeklika w Tarnowie	Tarnow	Malopolskie

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

Belgium,  Bulgaria,  Canada,  Hungary,  Latvia,  Lithuania,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Through Day 12
Secondary	Incidence of major bleeding	International Society on Thrombosis and Hemostasis (ISTH) criteria for Major Bleeding as described in the protocol	Up to approximately Day 12
Secondary	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	Up to approximately Day 12
Secondary	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	Through end of study; approximately Day 75
Secondary	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	Through Day 12
Secondary	Incidence of DVT	DVT will be measured by venography of the operated leg	Approximately Day 12
Secondary	Concentrations of REGN9933 in serum	The concentrations of REGN9933 over time will be summarized by descriptive statistics by study arm for the overall population	Through end of study; approximately Day 75
Secondary	Change in activated partial thromboplastin time (aPTT)	aPTT will be used to measure the anticipated anticoagulant effect of REGN9933	Baseline to end of study; approximately Day 75
Secondary	Change in prothrombin time (PT)	PT is a measure of extrinsic and/or common pathway function.	Baseline to end of study; approximately Day 75
Secondary	Incidence of anti-drug antibodies (ADA) to REGN9933	Immunogenicity will be characterized per drug molecule by ADA status	Through end of study; approximately Day 75
Secondary	Titer of anti-drug antibodies to REGN9933	Immunogenicity will be characterized per drug molecule by ADA status.	Through end of study; approximately Day 75
Secondary	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)	Baseline through Day 12