A Trial to Learn if Single Ascending Intravenous (IV) Doses of REGN7508 Are Safe and Well Tolerated, and How it Works in the Body of Healthy Adult Participants

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the safety and tolerability of single doses of REGN7508 in healthy adult participants The secondary objectives of the study are to: Evaluate the effects of single doses of REGN7508 on intrinsic/common pathway coagulation Evaluate the effects of single doses of REGN7508 on extrinsic/common pathway coagulation Characterize the drug concentration profiles and pharmacokinetics (PK) following single escalating doses of REGN7508 Characterize the concentration profiles of total Factor XI (FXI) following single escalating doses of REGN7508 Assess the immunogenicity of single doses of REGN7508

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single-Center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of REGN7508, a Monoclonal Antibody Against Factor XI, in Healthy Adult Subjects

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: REGN7508 (IV)
* Drug: REGN7508 (SC)
* Drug: Matching Placebo (IV)
* Drug: Matching Placebo (SC)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Body mass index between 18.0 and 32.5 kg/m2 (inclusive) at the screening visit Judged by the investigator to be in good health based on medical history, physical examination, vital sign measurements, and echocardiograms (ECGs) performed at screening and/or prior to administration of initial dose of study drug 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 Normal activated partial thromboplastin time (aPTT), normal prothrombin time (PT), and normal platelet counts at screening period and at the day -1 visit as defined by the local laboratory Hemoglobin value ≥11.0 g/dL for females and ≥12.9 g/dL for males at the screening and day 1 visits Key Exclusion Criteria: History of any major surgical procedure or clinically significant physical trauma, in the opinion of the investigator, that may pose a risk to the participant by study participation Whole blood donation within the previous 56 days or plasma donation within the previous 7 days prior to the screening visit History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, neurological, or dermatologic disease, as assessed by the investigator, that may confound the results of the study or poses an additional risk to the participant by study participation, as defined in the protocol Estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73m2 at screening Current smoker or former smoker, including e-cigarettes, who stopped smoking within 12 months prior to the screening visit 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 the screening visit History of alcohol abuse within the last 2 years prior to the day 1 visit 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 History of significant multiple and/or severe allergies (eg, latex gloves) or has had an anaphylactic reaction to prescription or nonprescription drugs or food NOTE: Other Protocol Defined Inclusion / Exclusion Criteria Apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 Lowest IV Dose<br>Randomized 3:1 | Drug: REGN7508 (IV)<br>* Administered sequential, ascending single intravenous (IV) dose<br>Drug: Matching Placebo (IV)<br>* Administered sequential, ascending single intravenous (IV) dose<br>|
| Experimental: Cohort 2 Low IV Dose<br>Randomized 3:1 | Drug: REGN7508 (IV)<br>* Administered sequential, ascending single intravenous (IV) dose<br>Drug: Matching Placebo (IV)<br>* Administered sequential, ascending single intravenous (IV) dose<br>|
| Experimental: Cohort 3 Mid IV Dose<br>Randomized 3:1 | Drug: REGN7508 (IV)<br>* Administered sequential, ascending single intravenous (IV) dose<br>Drug: Matching Placebo (IV)<br>* Administered sequential, ascending single intravenous (IV) dose<br>|
| Experimental: Cohort 4 High IV Dose<br>Randomized 3:1 | Drug: REGN7508 (IV)<br>* Administered sequential, ascending single intravenous (IV) dose<br>Drug: Matching Placebo (IV)<br>* Administered sequential, ascending single intravenous (IV) dose<br>|
| Experimental: Cohort 5 Higher IV Dose<br>Randomized 3:1 | Drug: REGN7508 (IV)<br>* Administered sequential, ascending single intravenous (IV) dose<br>Drug: Matching Placebo (IV)<br>* Administered sequential, ascending single intravenous (IV) dose<br>|
| Experimental: *Cohort 6 High SC Dose<br>Randomized 3:1 * SC Dose Cohort will be initiated only after an equivalent or higher IV Dose level has been evaluated. SC Cohort 6 and 7 may be activated prior to IV Dose Cohort 5. | Drug: REGN7508 (SC)<br>* Administered sequential, ascending single subcutaneous (SC) dose<br>Drug: Matching Placebo (SC)<br>* Administered sequential, ascending single subcutaneous (SC) dose<br>|
| Experimental: *Cohort 7 Higher SC Dose<br>Randomized 3:1 * SC Dose Cohort will be initiated only after an equivalent or higher IV Dose level has been evaluated. SC Cohort 6 and 7 may be activated prior to IV Dose Cohort 5. | Drug: REGN7508 (SC)<br>* Administered sequential, ascending single subcutaneous (SC) dose<br>Drug: Matching Placebo (SC)<br>* Administered sequential, ascending single subcutaneous (SC) dose<br>|
| Experimental: Optional: Cohort 8 Highest IV or SC Dose<br>Randomized 3:1 | Drug: REGN7508 (IV)<br>* Administered sequential, ascending single intravenous (IV) dose<br>Drug: REGN7508 (SC)<br>* Administered sequential, ascending single subcutaneous (SC) dose<br>Drug: Matching Placebo (IV)<br>* Administered sequential, ascending single intravenous (IV) dose<br>Drug: Matching Placebo (SC)<br>* Administered sequential, ascending single subcutaneous (SC) dose<br>|
| Experimental: Optional: Cohort 9 Highest IV or SC Dose<br>Randomized 3:1 | Drug: REGN7508 (IV)<br>* Administered sequential, ascending single intravenous (IV) dose<br>Drug: REGN7508 (SC)<br>* Administered sequential, ascending single subcutaneous (SC) dose<br>Drug: Matching Placebo (IV)<br>* Administered sequential, ascending single intravenous (IV) dose<br>Drug: Matching Placebo (SC)<br>* Administered sequential, ascending single subcutaneous (SC) dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidences of treatment-emergent adverse events (TEAE) | Treatment-emergent adverse events are defined as those that are not present at baseline or represent the exacerbation of a pre-existing condition during the on-treatment period. | Through the End of Outpatient Clinical Follow-up (EOF), Approximately 36 Days | 
| Severity of TEAE | Treatment-emergent adverse events are defined as those that are not present at baseline or represent the exacerbation of a pre-existing condition during the on-treatment period. | Through the EOF, Approximately 36 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in activated partial thromboplastin time (aPTT) |  | Baseline Through EOF, Approximately 36 Days | 
| Change from baseline in prothrombin time (PT) |  | Baseline Through EOF, Approximately 36 Days | 
| Concentrations of REGN7508 in serum |  | Through the EOF, Approximately 36 Days | 
| Change from baseline in total Factor XI (FXI) concentrations |  | Baseline Through the EOF, Approximately 36 Days | 
| Incidence of antidrug antibodies (ADAs) to REGN7508 over time |  | Through the EOF, Approximately 36 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thrombotic disorders