A trial to learn how well REGN9933 works for preventing blood clots after knee replacement surgery in adult participants

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Regeneron Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15], Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

26 Jun 2023 → 28 May 2024

Decision date (initial)

2023-07-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Regeneron Pharmaceuticals Inc.

External identifiers

EU CT number

2022-501470-18-00

ClinicalTrials.gov

NCT05618808

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Efficacy, Safety, Others

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.

Secondary objectives 8

1. 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
2. To assess overall safety and tolerability of REGN9933 in participants undergoing TKA
3. To evaluate the efficacy of REGN9933 in prevention of clinically relevant VTE, compared to enoxaparin
4. To evaluate the efficacy of REGN9933 in prevention of deep venous thrombosis (DVT) detected by venography, compared to enoxaparin
5. To evaluate the pharmacokinetics (PK) of REGN9933 after single intravenous (IV) administration
6. To assess pharmacodynamic (PD) effects of REGN9933 on intrinsic and extrinsic coagulation pathways
7. To assess immunogenicity following a single dose of REGN9933 over time
8. To compare the efficacy of enoxaparin and apixaban in prevention of VTE after unilateral TKA

Conditions and MedDRA coding

Thromboembolic disease

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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

Exclusion criteria 7

1. 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. 2. History of thromboembolic disease or thrombophilia.
3. 3. History of major surgery, including brain, spinal, or ocular, within approximately the past 6 months.
4. 4. History of major trauma within approximately the past 6 months.
5. 5. Hospitalized (>24 hours) for any reason within 30 days of the screening visit.
6. 6. Using the Modification of Diet in Renal Disease equation, has an estimated glomerular filtration rate as described in the protocol.
7. Other protocol-defined exclusion criteria apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the incidence of confirmed, adjudicated venous thromboembolism (VTE) through day 12 (REGN9933 vs enoxaparin).

Secondary endpoints 11

1. Incidence of major bleeding (up to approximately day 12).
2. Incidence of clinically relevant non-major (CRNM) bleeding (up to approximately day 12).
3. Incidence of treatment emergent adverse events (TEAEs) (through end of study; approximately day 75).
4. Incidence of major VTE through day 12 (REGN9933 versus enoxaparin).
5. Incidence of DVT as measured by venography of the operated leg (approximately day 12; REGN9933 vs enoxaparin).
6. Concentrations of REGN9933 in serum (through end of study; approximately day 75).
7. Change in activated partial thromboplastin time (aPTT) from baseline (through end of study; approximately day 75).
8. Change in prothrombin time (PT) from baseline (through end of study; approximately day 75).
9. Incidence of anti-drug antibodies (ADA) to REGN9933 (through end of study; approximately day 75).
10. Titer of anti-drug antibodies (ADA) to REGN9933 (through end of study; approximately day 75).
11. Incidence of confirmed, adjudicated VTE (baseline through day 12; enoxaparin vs apixaban).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Regeneron Pharmaceuticals Inc.

Sponsor organisation

Regeneron Pharmaceuticals Inc.

Address

777 Old Saw Mill River Road

City

Tarrytown

Postcode

10591-6717

Country

United States

Scientific contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Medical Affairs

Public contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Medical Affairs

Third parties 10

Locations

6 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications