Clinical trial NCT05102136: Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of REGN9933 in Adult Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: HV
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-11-01
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence and severity of treatment emergent adverse events (TEAE)
timeFrame: Until resolution of pharmacodynamic (PD) effects; approximately 36 days
Secondary outcomes:
measure: Change from baseline in activated partial thromboplastin time (aPTT)
timeFrame: Until resolution of PD effects; approximately 36 days
measure: Change from baseline in prothrombin time (PT)
timeFrame: Until resolution of PD effects; approximately 36 days
measure: Concentration of REGN9933 in serum
timeFrame: Until resolution of PD effects; approximately 36 days
measure: Change from baseline in total Factor XI (FXI) concentrations
timeFrame: Until resolution of PD effects; approximately 36 days
measure: The incidence of antidrug antibodies (ADAs) to REGN9933 over time
timeFrame: Until resolution of PD effects; approximately 36 days
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: Regeneron Study Site
state: Antwerp
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: