A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of REGN9035 in Healthy Adult Volunteers and Mildly Hypertensive 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 REGN5381 and REGN9035 administered alone or sequentially. The secondary objectives of the study are to: Evaluate the ability of single intravenous (IV) doses of REGN9035 (compared to placebo) to reverse the acute hemodynamic effects of REGN5381 Evaluate the hemodynamic effects of single IV doses of REGN5381 Evaluate the persistence of the hemodynamic effects of single IV doses of REGN5381 and the reversal of REGN5381 effects by REGN9035 (compared to placebo) Evaluate the pharmacokinetics of single IV doses of REGN5381 and REGN9035 administered alone or sequentially

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Two-Part, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of REGN9035 (an Anti-REGN5381 Antibody and Reversal Agent) and REGN5381 (an NPR1 Agonist Antibody) When Administered Alone or in Sequence to Healthy Volunteers and Mildly Hypertensive Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: REGN9035
* Drug: REGN5381
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Body mass index (BMI) between 18 and 32 kg/m2, inclusive, at the screening visit. Normal or mildly elevated blood pressure as defined in the protocol. Key Exclusion Criteria: History of unexplained syncope or autonomic dysfunction. History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, or neurological disease. Protocol-defined risk factors for cardiovascular disease. 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: Part A<br>Single ascending dose (SAD) of REGN9035 or matching placebo given by intravenous (IV) administration. | Drug: REGN9035<br>* Part A: Single dose administered by IV infusion on day 1. Part B: Selected doses administered by IV infusion on day 2 or 22.<br>Other: Placebo<br>* Part A: Single dose administered by IV infusion on day1. Part B: Single dose administered by IV infusion on day 1, day 2 and/or day 22.<br>|
| Experimental: Part B<br>Selected doses of REGN5381 or matching placebo given by IV administration followed by selected doses of REGN9035 and/or matching placebo via IV infusion | Drug: REGN9035<br>* Part A: Single dose administered by IV infusion on day 1. Part B: Selected doses administered by IV infusion on day 2 or 22.<br>Drug: REGN5381<br>* Part B: Selected doses administered by IV infusion on day 1.<br>Other: Placebo<br>* Part A: Single dose administered by IV infusion on day1. Part B: Single dose administered by IV infusion on day 1, day 2 and/or day 22.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Severity of Treatment Emergent Adverse Events (TEAEs) |  | Up to Day 162 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean systolic blood pressure (SBP) obtained after study drug administration | Up to 24 hours after study drug administration. | Up to Day 3 | 
| Mean diastolic blood pressure (DBP) obtained after study drug administration |  | Up to Day 3 | 
| Mean arterial pressure (MAP) obtained after study drug administration |  | Up to Day 3 | 
| Mean pulse pressure (PP) obtained after study drug administration |  | Up to Day 3 | 
| Mean pulse rate (PR) obtained after study drug administration |  | Up to Day 3 | 
| Mean stroke volume (SV) obtained after study drug administration |  | Up to Day 3 | 
| Absolute change in the mean SBP obtained after study drug administration |  | Up to Day 3 | 
| Absolute change in the mean DBP obtained after study drug administration |  | Up to Day 3 | 
| Absolute change in the mean MAP obtained after study drug administration |  | Up to Day 3 | 
| Absolute change in the mean PP obtained after study drug administration |  | Up to Day 3 | 
| Absolute change in the mean PR obtained after study drug administration |  | Up to Day 3 | 
| Absolute change in the mean SV obtained after study drug administration |  | Up to Day 3 | 
| Maximum change in the mean SBP obtained after study drug administration |  | Up to Day 3 | 
| Maximum change in the mean DBP obtained after study drug administration |  | Up to Day 3 | 
| Maximum change in the mean MAP obtained after study drug administration |  | Up to Day 3 | 
| Maximum change in the mean PP obtained after study drug administration |  | Up to Day 3 | 
| Maximum change in the mean PR obtained after study drug administration |  | Up to Day 3 | 
| Maximum change in the mean SV obtained after study drug administration |  | Up to Day 3 | 
| Percent change in the mean SBP obtained after study drug administration |  | Up to Day 3 | 
| Percent change in the mean DBP obtained after study drug administration |  | Up to Day 3 | 
| Percent change in the mean MAP obtained after study drug administration |  | Up to Day 3 | 
| Percent change in the mean PP obtained after study drug administration |  | Up to Day 3 | 
| Percent change in the mean PR obtained after study drug administration |  | Up to Day 3 | 
| Percent change in the mean SV obtained after study drug administration |  | Up to Day 3 | 
| Absolute change from baseline (post-REGN5381 administration) in the mean SBP obtained after study drug administration |  | Up to Day 3 | 
| Absolute change from baseline (post-REGN5381 administration) in the mean DBP obtained after study drug administration |  | Up to Day 3 | 
| Absolute change from baseline (post-REGN5381 administration) in the mean MAP obtained after study drug administration |  | Up to Day 3 | 
| Absolute change from baseline (post-REGN5381 administration) in the mean PP obtained after study drug administration |  | Up to Day 3 | 
| Absolute change from baseline (post-REGN5381 administration) in the mean PR obtained after study drug administration |  | Up to Day 3 | 
| Absolute change from baseline (post-REGN5381 administration) in the mean SV obtained after study drug administration |  | Up to Day 3 | 
| Maximum change from baseline (post-REGN administration) in the mean SBP obtained after study drug administration |  | Up to Day 3 | 
| Maximum change from baseline (post-REGN administration) in the mean DBP obtained after study drug administration |  | Up to Day 3 | 
| Maximum change from baseline (post-REGN administration) in the mean MAP obtained after study drug administration |  | Up to Day 3 | 
| Maximum change from baseline (post-REGN administration) in the mean PP obtained after study drug administration |  | Up to Day 3 | 
| Maximum change from baseline (post-REN5381 administration) in the mean PR obtained after study drug administration |  | Up to Day 3 | 
| Maximum change from baseline (post-REGN5381 administration) in the mean SV obtained after study drug administration |  | Up to Day 3 | 
| Percent change from baseline (post-REN5381 administration) in the mean SBP obtained after study drug administration |  | Up to Day 3 | 
| Percent change from baseline (post-REN5381 administration) in the mean DBP obtained after study drug administration |  | Up to Day 3 | 
| Percent change from baseline (post-REN5381 administration) in the mean MAP obtained after study drug administration |  | Up to Day 3 | 
| Percent change from baseline (post-REN5381 administration) in the mean PP obtained after study drug administration |  | Up to Day 3 | 
| Percent change from baseline (post-REN5381 administration) in the mean PR obtained after study drug administration |  | Up to Day 3 | 
| Percent change from baseline (post-REN5381 administration) in the mean SV obtained after study drug administration |  | Up to Day 3 | 
| Absolute change from baseline (pre-REGN5381 administration) in the mean SBP obtained after study drug administration |  | Up to Day 3 | 
| Absolute change from baseline (pre-REGN5381 administration) in the mean DBP obtained after study drug administration |  | Up to Day 3 | 
| Absolute change from baseline (pre-REGN5381 administration) in the mean MAP obtained after study drug administration |  | Up to Day 3 | 
| Absolute change from baseline (pre-REGN5381 administration) in the mean PP obtained after study drug administration |  | Up to Day 3 | 
| Absolute change from baseline (pre-REGN5381 administration) in the mean PR obtained after study drug administration |  | Up to Day 3 | 
| Absolute change from baseline (pre-REGN5381 administration) in the mean SV obtained after study drug administration |  | Up to Day 3 | 
| Maximum change from baseline (pre-REGN administration) in the mean SBP obtained after study drug administration |  | Up to Day 3 | 
| Maximum change from baseline (pre-REGN administration) in the mean DBP obtained after study drug administration |  | Up to Day 3 | 
| Maximum change from baseline (pre-REGN administration) in the mean MAP obtained after study drug administration |  | Up to Day 3 | 
| Maximum change from baseline (pre-REGN administration) in the mean PP obtained after study drug administration |  | Up to Day 3 | 
| Maximum change from baseline (pre-REGN administration) in the mean PR obtained after study drug administration |  | Up to Day 3 | 
| Maximum change from baseline (pre-REGN administration) in the mean SV obtained after study drug administration |  | Up to Day 3 | 
| Percent change from baseline (pre-REN5381 administration) in the mean SBP obtained after study drug administration |  | Up to Day 3 | 
| Percent change from baseline (pre-REN5381 administration) in the mean DBP obtained after study drug administration |  | Up to Day 3 | 
| Percent change from baseline (pre-REN5381 administration) in the mean MAP obtained after study drug administration |  | Up to Day 3 | 
| Percent change from baseline (pre-REN5381 administration) in the mean PP obtained after study drug administration |  | Up to Day 3 | 
| Percent change from baseline (pre-REN5381 administration) in the mean PR obtained after study drug administration |  | Up to Day 3 | 
| Percent change from baseline (pre-REN5381 administration) in the mean SV obtained after study drug administration |  | Up to Day 3 | 
| Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) SBP obtained after study drug administration. |  | Baseline to Day 3 | 
| Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) DBP obtained after study drug administration. |  | Baseline to Day 3 | 
| Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) MAP obtained after study drug administration. |  | Baseline to Day 3 | 
| Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) PP obtained after study drug administration. |  | Baseline to Day 3 | 
| Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) PR obtained after study drug administration. |  | Baseline to Day 3 | 
| Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) SV obtained after study drug administration. |  | Baseline to Day 3 | 
| Time to return to within 10% of baseline (pre-REGN5381) SBP |  | Up to approximately Day 162 | 
| Time to return to within 10% of baseline (pre-REGN5381) DBP |  | Up to approximately Day 162 | 
| Time to return to within 10% of baseline (pre-REGN5381) MAP |  | Up to approximately Day 162 | 
| Time to return to within 10% of baseline (pre-REGN5381) PP |  | Up to approximately Day 162 | 
| Time to return to within 10% of baseline (pre-REGN5381) PR |  | Up to approximately Day 162 | 
| Time to return to within 10% of baseline (pre-REGN5381) SV |  | Up to approximately Day 162 | 
| SBP |  | Through Day 36 | 
| DBP |  | Through Day 36 | 
| MAP |  | Through Day 36 | 
| PP |  | Through Day 36 | 
| PR |  | Through Day 36 | 
| Absolute change from baseline in SBP |  | Through Day 36 | 
| Absolute change from baseline in DBP |  | Through Day 36 | 
| Absolute change from baseline in MAP |  | Through Day 36 | 
| Absolute change from baseline in PP |  | Through Day 36 | 
| Absolute change from baseline in PR |  | Through Day 36 | 
| Percent change from baseline in SBP |  | Through Day 36 | 
| Percent change from baseline in DBP |  | Through Day 36 | 
| Percent change from baseline in MAP |  | Through Day 36 | 
| Percent change from baseline in PP |  | Through Day 36 | 
| Percent change from baseline in PR |  | Through Day 36 | 
| Concentrations of total REGN9035 |  | Up to Day 162 | 
| Concentrations of total REGN5381 over time |  | Up to Day 162 | 
| Concentrations of total REGN9035 and/or total REGN5381 |  | Up to Day 162 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Volunteers, Mild Hypertension, High Blood Pressure