A Trial to Learn How Well REGN9933 Works for Preventing Blood Clots After Knee Replacement Surgery in Adult Participants
- 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
- Short 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
- Control arm
- Active comparator
- Registry reports results
- Listing at source
- Listed
- Recruitment status
- Completed
- Phase
- Phase 2
- Study type
- Interventional
- Completion date
- 2024-05-27
- First posted
- 2022-11-16
- Registry last updated
- 2025-08-29
- Primary completion date
- 2024-05-27
- Start date
- 2023-05-24
- Actual participants
- Participants
- Participant count basis
- Actual
- Protocol amendments
- Number of sites
- Data monitoring committee
- Registry sponsor category
- Industry
- Lead sponsor
- Regeneron Pharmaceuticals
- Source registry
- ClinicalTrials.gov
- Registry ID
- NCT05618808
- ClinicalTrials.gov ID
- NCT05618808
- Registry record
- Open registry record
- Allocation
- Randomised
- Model
- Parallel groups
- Purpose
- Treatment
- Masking
- No masking
Percentage of Participants With Confirmed, Adjudicated Venous Thromboembolism (VTE) (REGN9933 vs Enoxaparin)
Timeframe: Through Day 12
Composite endpoint that includes: asymptomatic deep DVT (deep venous thrombosis) 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
Number of Participants With Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding
Timeframe: Through Day 12
International Society on Thrombosis and Hemostasis (ISTH) criteria for Major Bleeding and CRNM Bleeding as described in the protocol
Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE)
Timeframe: Up to Day 75
A TEAE is any untoward medical occurrence in a participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.
Percentage of Participants With Major VTE (REGN9933 vs Enoxaparin)
Timeframe: Through Day 12
Major VTE is a composite endpoint that includes: proximal DVT; confirmed symptomatic DVT of either leg; confirmed fatal or nonfatal PE including unexplained death for which PE cannot be ruled out
Percentage of Participants With DVT (REGN9933 vs Enoxaparin)
Timeframe: Through Day 12
DVT measured by venography of the operated leg
Total REGN9933 Concentrations in Serum
Timeframe: Days 0.0625 (post-dose), 4, 9, 29, and 74
The concentrations of REGN9933 over time were summarized by descriptive statistics by study arm for the overall population
Fold Change From Baseline in Activated Partial Thromboplastin Time (aPTT)
Timeframe: Days 1, 5, 10, 30, and 75
aPTT was used to measure the anticipated anticoagulant effect of REGN9933. Fold change is based on the follow-up value/baseline value within an arm.
Fold Change From Baseline in Prothrombin Time (PT)
Timeframe: Days 1, 5, 10, 30, and 75
PT is a measure of extrinsic and/or common pathway function. Fold change is based on the follow-up value/baseline value within an arm.
Number of Participants With Anti-REGN9933 Antibodies by Status
Timeframe: Through Day 75
Immunogenicity characterized by anti-drug antibody (ADA) status
Number of Participants With Treatment-Emergent or Treatment-Boosted Anti-REGN13335 Antibodies by Maximum Titer Level
Timeframe: Through Day 75
Immunogenicity characterized per drug molecule by ADA status
Percentage of Participants With Confirmed, Adjudicated VTE (Enoxaparin vs Apixaban)
Timeframe: Through Day 12
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.
- Sex
- All
- Age groups
- Adults, Older adults
- Minimum age
- 50 Years
- Healthy volunteers
- No
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
- Ziekenhuis Oost-Limburg- Campus Sint-JanGenk, Belgium
- MBAL Heart and Brain HospitalPleven, Bulgaria
- Durham Bone and Joint SpecialistsAjax, Canada
- MAV Korhaz es Rendelointezet SzolnokSzolnok, Hungary
- Department of Orthopedics, Somogy County Mór Kaposi Teaching HospitalKaposvár, Hungary
- Liepaja Regional HospitalLiepāja, Latvia
- Vidzemes HospitalRiga, Latvia
- Riga's 2nd HospitalRiga, Latvia
- Hospital of Traumatology and OrthopaedicsRiga, Latvia
- Lietuvos Sveikatos Mokslu Universiteto Ligonine Kauno KlinikKaunas, Lithuania
- Klaipeda University HospitalKlaipėda, Lithuania
- Lietuvos Sveikatos Mokslu Universiteto Kauno LigoninėKaunas, Lithuania
- Specjalistyczny Szpital im. E. Szczeklika w TarnowieTarnów, Poland
- SP ZOZ Centralny Szpital Kliniczny UM w LodziLodz, Poland
- Samodzielny Publiczny Szpital Kliniczny nr 4 w LublinieLublin, Poland
- Samodzielny Publiczny Zaklad Opieki Zdrowotnej w Radzyniu PodlaskimRadzyń Podlaski, Poland
- PubMed 41218619Related publication
- Related resource (roxi-vte.com)
- Related resource (www.trialsummaries.com)
Other registry identifiers
- 2022-501470-18-00
Related records
Drugs (1)
Lead sponsors (1)
Conditions (2)
- Thrombophilia due to thrombin defect
- Venous thromboembolism Primary condition