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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05102136
• Other study ID #: R9933-HV-2107
• Secondary ID: 2021-002568-34
• Status: Completed
• Phase: Phase 1
• Start date: October 27, 2021
• Est. completion date: April 4, 2023

Study information

• Verified date: April 2023
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: April 4, 2023
• Est. primary completion date: April 4, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• REGN9933
Administered intravenously (IV) or subcutaneous (SC) per the protocol
• Placebo
Placebo to match REGN9933 in same form; placebo administered IV or SC per the protocol

Locations

Country	Name	City	State
Belgium	Regeneron Study Site	Edegem	Antwerp

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of treatment emergent adverse events (TEAE)		Until resolution of pharmacodynamic (PD) effects; approximately 36 days
Secondary	Change from baseline in activated partial thromboplastin time (aPTT)		Until resolution of PD effects; approximately 36 days
Secondary	Change from baseline in prothrombin time (PT)		Until resolution of PD effects; approximately 36 days
Secondary	Concentration of REGN9933 in serum		Until resolution of PD effects; approximately 36 days
Secondary	Change from baseline in total Factor XI (FXI) concentrations		Until resolution of PD effects; approximately 36 days
Secondary	The incidence of antidrug antibodies (ADAs) to REGN9933 over time		Until resolution of PD effects; approximately 36 days