Trial Outcomes & Findings for A Trial to Learn How Well REGN9933 Works for Preventing Blood Clots After Knee Replacement Surgery in Adult Participants (NCT NCT05618808)

NCT ID: NCT05618808

Last Updated: 2025-08-29

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 373 participants
• Primary outcome timeframe: Through Day 12
• Results posted on: 2025-08-29

Participant Flow

A total of 450 participants were screened for study eligibility, and 77 participants discontinued during the screening period. 373 participants met eligibility criteria and were randomized into 1 of 3 treatment groups.

Participant milestones

Measure	REGN9933 REGN9933 was administered by intravenous (IV) infusion	Enoxaparin Enoxaparin was administered by subcutaneous (SC) administration	Apixaban Apixaban was administered orally twice a day
Overall Study STARTED	123	125	125
Overall Study COMPLETED	120	124	122
Overall Study NOT COMPLETED	3	1	3

Reasons for withdrawal

Measure	REGN9933 REGN9933 was administered by intravenous (IV) infusion	Enoxaparin Enoxaparin was administered by subcutaneous (SC) administration	Apixaban Apixaban was administered orally twice a day
Overall Study Withdrawal by Subject	3	1	3

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	REGN9933 n=123 Participants REGN9933 was administered by intravenous (IV) infusion	Enoxaparin n=125 Participants Enoxaparin was administered by subcutaneous (SC) administration	Apixaban n=125 Participants Apixaban was administered orally twice a day	Total n=373 Participants Total of all reporting groups
Age, Continuous	66.5 Years STANDARD_DEVIATION 7.73 • n=5 Participants	66.6 Years STANDARD_DEVIATION 7.61 • n=7 Participants	66.5 Years STANDARD_DEVIATION 7.69 • n=5 Participants	66.5 Years STANDARD_DEVIATION 7.66 • n=4 Participants
Sex: Female, Male Female	95 Participants n=5 Participants	104 Participants n=7 Participants	89 Participants n=5 Participants	288 Participants n=4 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	21 Participants n=7 Participants	36 Participants n=5 Participants	85 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	120 Participants n=5 Participants	121 Participants n=7 Participants	121 Participants n=5 Participants	362 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	123 Participants n=5 Participants	125 Participants n=7 Participants	125 Participants n=5 Participants	373 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Through Day 12

Population: Randomized participants in the REGN9933 and enoxaparin arms that had either an evaluable venogram, a confirmed episode of venous thromboembolism, or both.

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

Outcome measures

Measure	REGN9933 n=116 Participants REGN9933 was administered by intravenous (IV) infusion	Enoxaparin n=117 Participants Enoxaparin was administered by subcutaneous (SC) administration	Apixaban Apixaban was administered orally twice a day
Percentage of Participants With Confirmed, Adjudicated Venous Thromboembolism (VTE) (REGN9933 vs Enoxaparin)	17.2 percentage of participants	22.2 percentage of participants	—

SECONDARY outcome

Timeframe: Through Day 12

Population: Randomized participants that had either an evaluable venogram, a confirmed episode of venous thromboembolism, or both.

International Society on Thrombosis and Hemostasis (ISTH) criteria for Major Bleeding and CRNM Bleeding as described in the protocol

Outcome measures

Measure	REGN9933 n=116 Participants REGN9933 was administered by intravenous (IV) infusion	Enoxaparin n=117 Participants Enoxaparin was administered by subcutaneous (SC) administration	Apixaban n=113 Participants Apixaban was administered orally twice a day
Number of Participants With Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding	0 Participants	0 Participants	0 Participants

SECONDARY outcome

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.

Outcome measures

Measure	REGN9933 n=123 Participants REGN9933 was administered by intravenous (IV) infusion	Enoxaparin n=125 Participants Enoxaparin was administered by subcutaneous (SC) administration	Apixaban n=125 Participants Apixaban was administered orally twice a day
Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE)	22.0 percentage of participants	20.8 percentage of participants	24.8 percentage of participants

SECONDARY outcome

Timeframe: Through Day 12

Population: Randomized participants in the REGN9933 and enoxaparin arms that had either an evaluable venogram, a confirmed episode of venous thromboembolism, or both.

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

Outcome measures

Measure	REGN9933 n=116 Participants REGN9933 was administered by intravenous (IV) infusion	Enoxaparin n=117 Participants Enoxaparin was administered by subcutaneous (SC) administration	Apixaban Apixaban was administered orally twice a day
Percentage of Participants With Major VTE (REGN9933 vs Enoxaparin)	0 percentage of participants	2.6 percentage of participants	—

SECONDARY outcome

Timeframe: Through Day 12

Population: Randomized participants in the REGN9933 and enoxaparin arms that had either an evaluable venogram, a confirmed episode of venous thromboembolism, or both.

DVT measured by venography of the operated leg

Outcome measures

Measure	REGN9933 n=116 Participants REGN9933 was administered by intravenous (IV) infusion	Enoxaparin n=117 Participants Enoxaparin was administered by subcutaneous (SC) administration	Apixaban Apixaban was administered orally twice a day
Percentage of Participants With DVT (REGN9933 vs Enoxaparin)	17.2 percentage of participants	22.2 percentage of participants	—

SECONDARY outcome

Timeframe: Days 0.0625 (post-dose), 4, 9, 29, and 74

Population: All participants in the REGN9933 treatment group who received study drug and who had at least 1 non-missing result following the first dose of study drug and who were evaluable at time points specified for this outcome measure.

The concentrations of REGN9933 over time were summarized by descriptive statistics by study arm for the overall population

Outcome measures

Measure	REGN9933 n=123 Participants REGN9933 was administered by intravenous (IV) infusion	Enoxaparin Enoxaparin was administered by subcutaneous (SC) administration	Apixaban Apixaban was administered orally twice a day
Total REGN9933 Concentrations in Serum Day 0.0625 (post-dose)	65.6 milligrams/Liter (mg/L) Standard Deviation 18.2	—	—
Total REGN9933 Concentrations in Serum Day 4	34.9 milligrams/Liter (mg/L) Standard Deviation 9.65	—	—
Total REGN9933 Concentrations in Serum Day 9	23.7 milligrams/Liter (mg/L) Standard Deviation 7.15	—	—
Total REGN9933 Concentrations in Serum Day 29	5.51 milligrams/Liter (mg/L) Standard Deviation 3.47	—	—
Total REGN9933 Concentrations in Serum Day 74	0.140 milligrams/Liter (mg/L) Standard Deviation 0.107	—	—

SECONDARY outcome

Timeframe: Days 1, 5, 10, 30, and 75

Population: All randomized participants who received any study drug and who had at least 1 non-missing pharmacodynamic (PD) result following the first dose of study drug and who were evaluable at time points specified for this outcome measure.

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.

Outcome measures

Measure	REGN9933 n=123 Participants REGN9933 was administered by intravenous (IV) infusion	Enoxaparin n=125 Participants Enoxaparin was administered by subcutaneous (SC) administration	Apixaban n=123 Participants Apixaban was administered orally twice a day
Fold Change From Baseline in Activated Partial Thromboplastin Time (aPTT) Day 1	1.84 Fold Change Standard Deviation 0.245	—	—
Fold Change From Baseline in Activated Partial Thromboplastin Time (aPTT) Day 5	2.26 Fold Change Standard Deviation 0.309	1.11 Fold Change Standard Deviation 0.143	1.16 Fold Change Standard Deviation 0.163
Fold Change From Baseline in Activated Partial Thromboplastin Time (aPTT) Day 10	2.17 Fold Change Standard Deviation 0.443	1.04 Fold Change Standard Deviation 0.114	1.10 Fold Change Standard Deviation 0.117
Fold Change From Baseline in Activated Partial Thromboplastin Time (aPTT) Day 30	1.56 Fold Change Standard Deviation 0.385	1.01 Fold Change Standard Deviation 0.149	1.04 Fold Change Standard Deviation 0.129
Fold Change From Baseline in Activated Partial Thromboplastin Time (aPTT) Day 75	1.01 Fold Change Standard Deviation 0.132	1.01 Fold Change Standard Deviation 0.119	1.03 Fold Change Standard Deviation 0.120

SECONDARY outcome

Timeframe: Days 1, 5, 10, 30, and 75

Population: All randomized participants who received any study drug and who had at least 1 non-missing pharmacodynamic (PD) result following the first dose of study drug and who were evaluable at time points specified for this outcome measure.

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.

Outcome measures

Measure	REGN9933 n=123 Participants REGN9933 was administered by intravenous (IV) infusion	Enoxaparin n=125 Participants Enoxaparin was administered by subcutaneous (SC) administration	Apixaban n=123 Participants Apixaban was administered orally twice a day
Fold Change From Baseline in Prothrombin Time (PT) Day 1	1.01 Fold Change Standard Deviation 0.075	—	—
Fold Change From Baseline in Prothrombin Time (PT) Day 5	0.96 Fold Change Standard Deviation 0.086	0.94 Fold Change Standard Deviation 0.064	1.02 Fold Change Standard Deviation 0.091
Fold Change From Baseline in Prothrombin Time (PT) Day 10	0.95 Fold Change Standard Deviation 0.108	0.94 Fold Change Standard Deviation 0.073	1.00 Fold Change Standard Deviation 0.089
Fold Change From Baseline in Prothrombin Time (PT) Day 30	0.99 Fold Change Standard Deviation 0.220	0.97 Fold Change Standard Deviation 0.122	0.99 Fold Change Standard Deviation 0.183
Fold Change From Baseline in Prothrombin Time (PT) Day 75	0.94 Fold Change Standard Deviation 0.145	0.93 Fold Change Standard Deviation 0.092	0.94 Fold Change Standard Deviation 0.073

SECONDARY outcome

Timeframe: Through Day 75

Population: All participants who received study drug REGN9933 and had at least 1 non-missing ADA result following the first dose of study drug

Immunogenicity characterized by anti-drug antibody (ADA) status

Outcome measures

Measure	REGN9933 n=119 Participants REGN9933 was administered by intravenous (IV) infusion	Enoxaparin Enoxaparin was administered by subcutaneous (SC) administration	Apixaban Apixaban was administered orally twice a day
Number of Participants With Anti-REGN9933 Antibodies by Status Negative	118 Participants	—	—
Number of Participants With Anti-REGN9933 Antibodies by Status Pre-existing Immunoreactivity	1 Participants	—	—
Number of Participants With Anti-REGN9933 Antibodies by Status Treatment-emergent (TE) Response	0 Participants	—	—
Number of Participants With Anti-REGN9933 Antibodies by Status Treatment-boosted (TB) Response	0 Participants	—	—

SECONDARY outcome

Timeframe: Through Day 75

Population: All participants who received study drug REGN9933 and had at least 1 non-missing ADA result following the first dose of study drug

Immunogenicity characterized per drug molecule by ADA status

Outcome measures

Measure	REGN9933 n=119 Participants REGN9933 was administered by intravenous (IV) infusion	Enoxaparin Enoxaparin was administered by subcutaneous (SC) administration	Apixaban Apixaban was administered orally twice a day
Number of Participants With Treatment-Emergent or Treatment-Boosted Anti-REGN13335 Antibodies by Maximum Titer Level Low (<1,000)	0 Participants	—	—
Number of Participants With Treatment-Emergent or Treatment-Boosted Anti-REGN13335 Antibodies by Maximum Titer Level Moderate (1,000 to 10,000)	0 Participants	—	—
Number of Participants With Treatment-Emergent or Treatment-Boosted Anti-REGN13335 Antibodies by Maximum Titer Level High (>10,000)	0 Participants	—	—

SECONDARY outcome

Timeframe: Through Day 12

Population: Randomized participants in the enoxaparin and apixaban arms that had either an evaluable venogram, a confirmed episode of venous thromboembolism, or both.

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.

Outcome measures

Measure	REGN9933 n=117 Participants REGN9933 was administered by intravenous (IV) infusion	Enoxaparin n=113 Participants Enoxaparin was administered by subcutaneous (SC) administration	Apixaban Apixaban was administered orally twice a day
Percentage of Participants With Confirmed, Adjudicated VTE (Enoxaparin vs Apixaban)	22.2 percentage of participants	12.4 percentage of participants	—

Adverse Events

REGN9933

Serious events: 4 serious events

Other events: 9 other events

Deaths: 0 deaths

Enoxaparin

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Apixaban

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	REGN9933 n=123 participants at risk REGN9933 was administered by intravenous (IV) infusion	Enoxaparin n=125 participants at risk Enoxaparin was administered by subcutaneous (SC) administration	Apixaban n=125 participants at risk Apixaban was administered orally twice a day
Cardiac disorders Atrial fibrillation	0.81% 1/123 • Number of events 1 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)	0.00% 0/125 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)	0.00% 0/125 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)
Cardiac disorders Angina pectoris	0.00% 0/123 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)	0.00% 0/125 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)	0.80% 1/125 • Number of events 1 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)
Hepatobiliary disorders Cholecystitis	0.81% 1/123 • Number of events 1 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)	0.00% 0/125 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)	0.00% 0/125 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)
Infections and infestations Device related infection	0.81% 1/123 • Number of events 1 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)	0.00% 0/125 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)	0.00% 0/125 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)
Infections and infestations Soft tissue infection	0.00% 0/123 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)	0.80% 1/125 • Number of events 1 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)	0.00% 0/125 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)
Renal and urinary disorders Urinary retention	0.81% 1/123 • Number of events 1 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)	0.00% 0/125 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)	0.00% 0/125 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/123 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)	0.00% 0/125 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)	0.80% 1/125 • Number of events 1 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)

Other adverse events

Measure	REGN9933 n=123 participants at risk REGN9933 was administered by intravenous (IV) infusion	Enoxaparin n=125 participants at risk Enoxaparin was administered by subcutaneous (SC) administration	Apixaban n=125 participants at risk Apixaban was administered orally twice a day
Injury, poisoning and procedural complications Anaemia postoperative	7.3% 9/123 • Number of events 9 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)	8.8% 11/125 • Number of events 11 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)	12.8% 16/125 • Number of events 16 • From date of signing informed consent form (ICF) up to end of study (approximately 105 days)

Additional Information

Clinical Trials Administrator

Regeneron Pharmaceuticals, Inc.

Phone: 844-734-6643

Email: clinicaltrials@regeneron.com

Results disclosure agreements

• Principal investigator is a sponsor employee The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
• Publication restrictions are in place

Restriction type: OTHER