Study to Assess the Safety, Tolerability, and Pharmacokinetics of REGN5381 (an NPR1 Agonist) in Adult Humans

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 intravenous (IV) doses of REGN5381 in healthy normotensive and otherwise healthy hypertensive adults. The secondary objectives of the study are: To evaluate the effect of single IV doses of REGN5381 on blood pressure (BP) and heart rate (HR) in healthy normotensive and otherwise healthy hypertensive adults To evaluate the effect of single IV doses of REGN5381 on cardiac stroke volume (SV) To evaluate the pharmacokinetics (PK) of single IV doses of REGN5381 To evaluate the immunogenicity of single IV doses of REGN5381

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Two-Part Single Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of REGN5381 (an NPR1 Agonist) in Humans

Conditions
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Healthy

Intervention / Treatment
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* Drug: REGN5381
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Normal or mildly elevated blood pressure as defined in the protocol Exclusion Criteria: History of cardiovascular disease as defined in the protocol Protocol-defined risk factors for cardiovascular disease History of unexplained syncope, autonomic dysfunction, or neurologic disease. NOTE: Additional 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: REGN5381<br>Single dose REGN5381 administered via IV infusion | Drug: REGN5381<br>* Single dose REGN5381 administered via IV infusion<br>|
| Other: Placebo<br>Placebo matching single dose REGN 5381 administered via IV infusion | Other: Placebo<br>* Placebo matching single dose REGN 5381 administered via IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events |  | Up to Day 78 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Systolic Blood Pressure (SBP) |  | Up to Day 78 | 
| Change from baseline in Diastolic Blood Pressure (DBP) |  | Up to Day 78 | 
| Change from baseline in Mean Arterial Pressure (MAP) |  | Baseline to Day 4 | 
| Change from baseline in Pulse Pressure (PP) |  | Baseline to Day 4 | 
| Change from baseline in Heart Rate (HR) |  | Up to Day 78 | 
| Change from baseline in Stroke Volume (SV) |  | Baseline to Day 4 | 
| Maximum change from baseline in SBP across the first 24 hours postdose |  | Baseline to Day 2 (24-hours post dose) | 
| Maximum change from baseline in DBP across the first 24 hours postdose |  | Baseline to Day 2 (24-hours post dose) | 
| Maximum change from baseline in MAP across the first 24 hours postdose |  | Baseline to Day 2 (24-hours post dose) | 
| Maximum change from baseline in PP across the first 24 hours postdose |  | Baseline to Day 2 (24-hours post dose) | 
| Maximum change from baseline in HR across the first 24 hours postdose |  | Baseline to Day 2 (24-hours post dose) | 
| Maximum change from baseline in SV across the first 24 hours postdose |  | Baseline to Day 2 (24-hours post dose) | 
| Change from baseline in the 24-hour mean SBP measured from 0 to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose | Baseline 24-hour mean SBP is measured from 0 to 24 hours pre-dose | Baseline to 24 hours postdose, 24 hours to 48 hours postdose, 48 hours to 72 hours postdose | 
| Change from baseline in the 24-hour mean DBP measured from 0 to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose | Baseline 24-hour mean DBP is measured from 0 to 24 hours pre-dose | Baseline to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose | 
| Change from baseline in the 24-hour mean MAP measured from 0 to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose | Baseline 24-hour mean MAP is measured from 0 to 24 hours pre-dose | Baseline to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose | 
| Change from baseline in the 24-hour mean PP measured from 0 to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose | Baseline 24-hour mean PP is measured from 0 to 24 hours pre-dose | Baseline to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose | 
| Change from baseline in the 24-hour mean HR measured from 0 to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose | Baseline 24-hour mean HR is measured from 0 to 24 hours pre-dose | Baseline to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose | 
| Concentrations of REGN5381 over time |  | Up to Day 78 | 
| Number of subjects who develop anti-drug antibodies (ADA) and titers |  | Up to Day 78 | 
| Percentage of subjects who develop anti-drug antibodies (ADA) and titers |  | Up to Day 78 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Normal Blood Pressure (BP), Mildly Elevated BP