Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of REGN9933 in Adult Healthy Volunteers

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single-Center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of REGN9933, a Monoclonal Antibody Against Factor XI, in Healthy Adult Subjects

The primary objective of the study is to evaluate the safety and tolerability of single doses of REGN9933 in healthy participants

The secondary objectives of the study are to:

• Evaluate the effects of single doses of REGN9933 on intrinsic/common pathway coagulation
• Evaluate the effects of single doses of REGN9933 on extrinsic/common pathway coagulation
• Characterize the drug concentration profiles and pharmacokinetic (PK) following single escalating doses of REGN9933
• Characterize the concentration profiles of total FXI following single escalating doses of REGN9933
• Assess the immunogenicity of single doses of REGN9933

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: REGN9933; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Antwerp
    • Edegem, Antwerp, Belgium, B-2650
      • Regeneron Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

1. Body mass index between 18.0 and 32.5 kilograms/per metered squared (kg/m^2) (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 electrocardiogram (ECGs) performed at screening and/or prior to administration of initial dose of study drug.
3. Participant is in good health based on laboratory safety testing obtained at the screening visit and/or prior to administration of initial dose of study drug. Note :Participant with suspected or confirmed Gilbert's disease can be enrolled in the study.
4. Normal activated partial thromboplastin time (aPTT), normal prothrombin time (PT), and normal platelet counts at screening period and at day -1 as defined by the local laboratory
5. Hemoglobin value ≥11.0 grams per deciliter (g/dL) for females and ≥12.9 g/dL for males at screening and day -1
6. Negative fecal occult blood test (FOBT) during screening period
7. Normal Bleeding time test (BTT) at day -1 as defined by the study site

Key Exclusion Criteria:

1. History of any major surgical procedure or clinically significant physical trauma, in the opinion of the investigator, that may pose a risk to the subject by study participation.
2. Whole blood donation within the previous 56 days or plasma donation within the previous 7 days prior to screening
3. Pregnant or breastfeeding women
4. History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, neurological, or dermatologic disease, as assessed by the investigator
5. Hospitalized for any reason within 30 days of the screening visit.
6. Current smoker or former smoker, including e-cigarettes, who stopped smoking within 12 months prior to the screening visit
7. Confirmed positive drug test result at the screening visit and/or prior to randomization or a history of drug abuse within a year prior to screening.
8. History of alcohol abuse within the last 2 years prior to dosing
9. Positive for human immunodeficiency virus (HIV), hepatitis B, or and/or hepatitis C per protocol resolved hepatitis B infection is not an exclusion.
10. Any malignancy, except for nonmelanoma skin cancer or cervical/anus in situ, that have been resected with no evidence of metastatic disease for 3 years prior to the screening visit
11. Women of child bearing potential (defined as women who are fertile, following menarche until becoming postmenopausal, unless permanently surgically sterile. The only allowed permanent sterilization methods for this study are hysterectomy and/or bilateral oophorectomy.)

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: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous Cohorts; Randomized 6:2 to REGN9933 or placebo	Drug: REGN9933; Administered intravenously (IV) or subcutaneous (SC) per the protocol; Drug: Placebo; Placebo to match REGN9933 in same form; placebo administered IV or SC per the protocol
Experimental: Subcutaneous Cohorts; Randomized 6:2 to REGN9933 or placebo	Drug: REGN9933; Administered intravenously (IV) or subcutaneous (SC) per the protocol; Drug: Placebo; Placebo to match REGN9933 in same form; placebo administered IV or SC per the protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and severity of treatment emergent adverse events (TEAE)	Until resolution of pharmacodynamic (PD) effects; approximately 36 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in activated partial thromboplastin time (aPTT)	Until resolution of PD effects; approximately 36 days
Change from baseline in prothrombin time (PT)	Until resolution of PD effects; approximately 36 days
Concentration of REGN9933 in serum	Until resolution of PD effects; approximately 36 days
Change from baseline in total Factor XI (FXI) concentrations	Until resolution of PD effects; approximately 36 days
The incidence of antidrug antibodies (ADAs) to REGN9933 over time	Until resolution of PD effects; approximately 36 days

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2021
• Primary Completion (Actual): April 4, 2023
• Study Completion (Actual): April 4, 2023

Study Registration Dates

• First Submitted: October 19, 2021
• First Submitted That Met QC Criteria: October 19, 2021
• First Posted (Actual): November 1, 2021

Study Record Updates

• Last Update Posted (Actual): May 3, 2023
• Last Update Submitted That Met QC Criteria: May 1, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: HV
• Other Study ID Numbers: R9933-HV-2107; 2021-002568-34 (EudraCT Number)

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, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has 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: No
• Studies a U.S. FDA-regulated device product: No