Venous ThromboembolismPhase 2NCT05618808
A Trial to Learn How Well REGN9933 Works for Preventing Blood Clots After Knee Replacement Surgery in Adult Participants
A Phase 2 study testing REGN9933, Enoxaparin and Apixiban in people with Venous Thromboembolism, run by Regeneron Pharmaceuticals at 16 sites in 7 countries.
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… Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Venous Thromboembolism
- What is being tested?
- REGN9933, Enoxaparin and Apixiban
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 373 participants
- Where
- 16 sitesin 7 countries
- Study dates
- 24 May 2023to 27 May 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
16 sites in 7 countries.
16 sites in 7 countries
Latvia4 sites
Liepaja Regional Hospital
Liepāja, LV3414
Vidzemes Hospital
Riga, LV-1002
Riga's 2nd Hospital
Riga, LV-1004
Hospital of Traumatology and Orthopaedics
Riga, LV1005
Poland4 sites
SP ZOZ Centralny Szpital Kliniczny UM w Lodzi
Lodz, 90-153
Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie
Lublin, 20-954
Samodzielny Publiczny Zaklad Opieki Zdrowotnej w Radzyniu Podlaskim
Radzyń Podlaski, 21-300
Specjalistyczny Szpital im. E. Szczeklika w Tarnowie
Tarnów, Lesser Poland Voivodeship, 33-100
Lithuania3 sites
Lietuvos Sveikatos Mokslu Universiteto Ligonine Kauno Klinik
Kaunas, Kaunas County, LT-50009
Lietuvos Sveikatos Mokslu Universiteto Kauno Ligoninė
Kaunas, LT-44320
Klaipeda University Hospital
Klaipėda, Klaipėda County, LT-92288
Hungary2 sites
Department of Orthopedics, Somogy County Mór Kaposi Teaching Hospital
Kaposvár, 7400
MAV Korhaz es Rendelointezet Szolnok
Szolnok, Jász-Nagykun-Szolnok, 5000
About this study
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
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
- Conditions
- Venous Thromboembolism
- Being tested
- REGN9933, Enoxaparin, Apixiban
- Keywords
- Anti-factor XI (FXI) monoclonal antibody, Deep Vein Thrombosis, Unilateral total knee arthroplasty (TKA),
- Medical subject headings
- Venous Thromboembolism, Venous Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
REGN9933Drug
Participants will receive a single dose of REGN9933 by IV infusion
EnoxaparinDrug
Also called Lovenox
Participants will receive enoxaparin by SC administration daily through the time of venography (or day 12, whichever is earlier)
ApixibanDrug
Also called Eliquis
Participants will receive apixaban orally twice a day through the time of venography (or day 12, whichever is earlier)
| Study group | Role | What they receive |
|---|---|---|
| REGN9933 | Experimental | REGN9933 will be administered by intravenous (IV) infusion Receives: Drug: REGN9933 |
| Enoxaparin | Active comparator | Enoxaparin will be administered by subcutaneous (SC) administration Receives: Drug: Enoxaparin |
| Apixaban | Active comparator | Apixaban will be administered orally twice a day Receives: Drug: Apixiban |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Confirmed, Adjudicated Venous Thromboembolism (VTE) (REGN9933 vs Enoxaparin)
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
Measured: Through Day 12
Secondary outcomes (10)
Number of Participants With Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding
International Society on Thrombosis and Hemostasis (ISTH) criteria for Major Bleeding and CRNM Bleeding as described in the protocol
Measured: Through Day 12
Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE)
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.
Measured: Up to Day 75
Percentage of Participants With Major VTE (REGN9933 vs Enoxaparin)
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
Measured: Through Day 12
Percentage of Participants With DVT (REGN9933 vs Enoxaparin)
DVT measured by venography of the operated leg
Measured: Through Day 12
Total REGN9933 Concentrations in Serum
The concentrations of REGN9933 over time were summarized by descriptive statistics by study arm for the overall population
Measured: Days 0.0625 (post-dose), 4, 9, 29, and 74
Fold Change From Baseline in Activated Partial Thromboplastin Time (aPTT)
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.
Measured: Days 1, 5, 10, 30, and 75
Fold Change From Baseline in Prothrombin Time (PT)
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.
Measured: Days 1, 5, 10, 30, and 75
Number of Participants With Anti-REGN9933 Antibodies by Status
Immunogenicity characterized by anti-drug antibody (ADA) status
Measured: Through Day 75
Number of Participants With Treatment-Emergent or Treatment-Boosted Anti-REGN13335 Antibodies by Maximum Titer Level
Immunogenicity characterized per drug molecule by ADA status
Measured: Through Day 75
Percentage of Participants With Confirmed, Adjudicated VTE (Enoxaparin vs Apixaban)
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.
Measured: Through Day 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2022
- Study start24 May 2023
- Primary completion27 May 2024
- Study completion27 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Venous ThromboembolismStudies of the same condition, open and under way.
- More trials run by Regeneron PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 373 participants (actual)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Management, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05618808
- Sponsor's protocol ID
- R9933-DVT-2230
- Other IDs
- 2022-501470-18-00
- Status last verified
- Aug 2025
- First submitted
- 8 Nov 2022
- Last updated
- 29 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Publications
Weitz JI, Kithcart AP, O'Brien MP, Levy O, Marin E, Onisko M, Mohammadi KA, Li D, Meagher KA, Chang HH, Olenchock BA, Gutstein DE, Segers A, Roberts RS, Bonaca MP, Raskob GE. Efficacy and safety of REGN9933A2 and REGN7508Cat for preventing postoperative venous thromboembolism (ROXI-VTE-I and ROXI-VTE-II): two randomised, open-label, phase 2 trials. Lancet. 2025 Nov 29;406(10519):2551-2563. doi: 10.1016/S0140-6736(25)02097-5. Epub 2025 Nov 8.
PubMed 41218619
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05618808
- Acronym / sponsor ID
- R9933-DVT-2230
- Conditions
- Venous Thromboembolism
- Keywords
- Anti-factor XI (FXI) monoclonal antibody, Deep Vein Thrombosis, Unilateral total knee arthroplasty (TKA),
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 373 participants (actual)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 24 May 2023 (actual)
- Primary completion
- 27 May 2024 (actual)
- Study completion
- 27 May 2024 (actual)
- First posted
- 16 Nov 2022 (actual)
- Results
- Posted 16 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| REGN9933 | Experimental | Drug: REGN9933REGN9933 will be administered by intravenous (IV) infusion |
| Enoxaparin | Active comparator | Drug: EnoxaparinEnoxaparin will be administered by subcutaneous (SC) administration |
| Apixaban | Active comparator | Drug: ApixibanApixaban will be administered orally twice a day |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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 (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| REGN9933Participants will receive a single dose of REGN9933 by IV infusion | Drug | REGN9933 |
| EnoxaparinAlso: LovenoxParticipants will receive enoxaparin by SC administration daily through the time of venography (or day 12, whichever is earlier) | Drug | Enoxaparin |
| ApixibanAlso: EliquisParticipants will receive apixaban orally twice a day through the time of venography (or day 12, whichever is earlier) | Drug | Apixaban |
Primary outcome
Percentage of Participants With Confirmed, Adjudicated Venous Thromboembolism (VTE) (REGN9933 vs Enoxaparin)
Time frame: 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
10 secondary outcomes
Number of Participants With Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding
Time frame: Through Day 12
Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE)
Time frame: Up to Day 75
Percentage of Participants With Major VTE (REGN9933 vs Enoxaparin)
Time frame: Through Day 12
Percentage of Participants With DVT (REGN9933 vs Enoxaparin)
Time frame: Through Day 12
Total REGN9933 Concentrations in Serum
Time frame: Days 0.0625 (post-dose), 4, 9, 29, and 74
Fold Change From Baseline in Activated Partial Thromboplastin Time (aPTT)
Time frame: Days 1, 5, 10, 30, and 75
Fold Change From Baseline in Prothrombin Time (PT)
Time frame: Days 1, 5, 10, 30, and 75
Number of Participants With Anti-REGN9933 Antibodies by Status
Time frame: Through Day 75
Number of Participants With Treatment-Emergent or Treatment-Boosted Anti-REGN13335 Antibodies by Maximum Titer Level
Time frame: Through Day 75
Percentage of Participants With Confirmed, Adjudicated VTE (Enoxaparin vs Apixaban)
Time frame: Through Day 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41218619Weitz JI, Kithcart AP, O'Brien MP, Levy O, Marin E, Onisko M, Mohammadi KA, Li D, Meagher KA, Chang HH, Olenchock BA, Gutstein DE, Segers A, Roberts RS, Bonaca MP, Raskob GE. Efficacy and safety of REGN9933A2 and REGN7508Cat for preventing postoperative venous thromboembolism (ROXI-VTE-I and ROXI-VTE-II): two randomised, open-label, phase 2 trials. Lancet. 2025 Nov 29;406(10519):2551-2563. doi: 10.1016/S0140-6736(25)02097-5. Epub 2025 Nov 8.
- Related InfoLink provided by the sponsor.
- A Plain Language Summary is available on TrialSummaries.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trial Management study director
Regeneron Pharmaceuticals
16 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing REGN9933, Enoxaparin and Apixiban in people with Venous Thromboembolism, run by Regeneron Pharmaceuticals at 16 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Latvia, Poland, Lithuania, Hungary, Belgium and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Confirmed, Adjudicated Venous Thromboembolism (VTE) (REGN9933 vs Enoxaparin) (time frame: Through Day 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05618808, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2025.