Assessment of Gastrointestinal Blood Loss After Receiving Aspirin or Aspirin Plus Rivaroxaban, or Aspirin Plus REGN9933, or Aspirin Plus REGN7508 in Healthy Adult Participants

A Parallel Group Study in Healthy Participants to Quantitate Increases in Subclinical Gastrointestinal Blood Loss Following Administration of Aspirin Alone or in Combination With Rivaroxaban or Factor XI Inhibitors (REGN9933 or REGN7508)

This study is researching experimental drugs called REGN9933 and REGN7508 (called "study drugs") and comparing their effects to approved treatments of rivaroxaban and aspirin (called "standard treatments"). Aspirin will be given alone or in combination with the study drugs or the other standard treatments to look at their effects on blood loss in the intestines.

The aim of the study is to see if aspirin alone or the study drugs REGN9933 and REGN7508, when taken with aspirin, cause less minor intestinal bleeding than standard treatments rivaroxaban with aspirin.

The study is looking at several other research questions, including:

• What side effects may happen from taking the study drug
• How much study drug is in the blood at different times
• Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Aspirin; Drug: REGN9933; Drug: REGN7508; Drug: Rivaroxaban

• Study Type: Interventional
• Enrollment (Actual): 224
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS11 9EH
    • Fortrea Clinical Development

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

1. Body mass index between 18.0 and 32.5 kg/m2 (inclusive) at the screening visit
2. Judged by the investigator to be in good health based on medical history, physical examination, vital sign measurements, and electrocardiograms (ECGs) performed at screening and/or prior to administration of initial dose of study treatment
3. Normal aPTT, normal PT, and normal platelet counts at screening period and at the day 1 visit as defined by the local laboratory
4. Hemoglobin values within the normal range, per local laboratory, at the screening and day 1 visits
5. Negative FOBT at Baseline (visit 2) and visit 3 as defined in the protocol

Key Exclusion Criteria:

1. History of any major surgical procedure or clinically significant physical trauma in the last 6 months, in the opinion of the investigator, that may pose a risk to the participant by study participation
2. Whole blood donation within the previous 56 days or plasma donation within the previous 7 days prior to the screening visit
3. Hospitalized for any reason within 30 days of the screening visit
4. Estimated glomerular filtrate rate (eGFR) of <60 mL/min/1.73m2 at screening as described in the protocol.
5. Current smoker or former smoker, including e-cigarettes, who stopped smoking within 12 months prior to the screening visit
6. History of illicit drug or alcohol abuse within the last 2 years prior to the day 1 visit
7. Use of any prescription and nonprescription medications or nutritional supplements from approximately 2 weeks or 5 half-lives, as described in protocol
8. Has elective surgery planned to occur prior to end of study (EOS)

Note: Other Protocol Defined Inclusion/ Exclusion Criteria Apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1: Aspirin; Randomized 1:1:1:1	Drug: Aspirin; Oral administration
Experimental: Arm 2: Aspirin + REGN9933; Randomized 1:1:1:1	Drug: Aspirin; Oral administration; Drug: REGN9933; Administered intravenous (IV)
Experimental: Arm 3: Aspirin + REGN7508; Randomized 1:1:1:1	Drug: Aspirin; Oral administration; Drug: REGN7508; Administered IV
Active Comparator: Arm 4: Aspirin + Rivaroxaban; Randomized 1:1:1:1	Drug: Aspirin; Oral administration; Drug: Rivaroxaban; Oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in fecal hemoglobin content (FHC)	Baseline and up to day 22

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of treatment-emergent adverse events (TEAE)	Up to day 100
Severity of TEAE	Up to day 100
Incidence of major bleeding	Up to day 100
Incidence of clinically relevant non-major (CRNM) bleeding	Up to day 100
Concentrations of REGN9933	Up to day 29
Concentrations of REGN7508	Up to day 29
Change in activated partial thromboplastin time (aPTT)	Baseline and up day 29
Change in prothrombin time (PT)	Baseline and up day 29
Incidence of Anti-drug antibody (ADA) to REGN9933	Up to day 29
Titer of ADA to REGN9933	Up to day 29
Incidence of ADA to REGN7508	Up to day 29
Titer of ADA to REGN7508	Up to day 29

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2024
• Primary Completion (Actual): April 7, 2025
• Study Completion (Actual): July 9, 2025

Study Registration Dates

• First Submitted: May 30, 2024
• First Submitted That Met QC Criteria: May 30, 2024
• First Posted (Actual): June 5, 2024

Study Record Updates

• Last Update Posted (Actual): July 16, 2025
• Last Update Submitted That Met QC Criteria: July 15, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Fecal occult blood testing (FOBT); Gastrointestinal (GI) bleeding
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Protease Inhibitors; Enzyme Inhibitors; Fibrin Modulating Agents; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Anticoagulants; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Rivaroxaban; Aspirin
• Other Study ID Numbers: R9933-HV-2424

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes