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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: REGN5381; Other: Placebo

• Registration Number: NCT04506645
• Lead Sponsor: Regeneron Pharmaceuticals

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-07-28
• Study First Submitted QC: 2020-08-07
• Study First Posted: 2020-08-10
• Study Start: 2020-09-01
• Status Verified: 2022-12
• Primary Completion: 2022-12-14
• Study Completion: 2022-12-14
• Last Update Submitted: 2022-12-19
• Last Update Posted: 2022-12-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. Normal or mildly elevated blood pressure as defined in the protocol

Exclusion Criteria

1. History of cardiovascular disease as defined in the protocol
2. Protocol-defined risk factors for cardiovascular disease
3. History of unexplained syncope, autonomic dysfunction, or neurologic disease.

NOTE: Additional Inclusion / Exclusion criteria apply

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
REGN5381	REGN5381	Single dose REGN5381 administered via IV infusion
Placebo	Placebo	Placebo matching single dose REGN 5381 administered via IV infusion

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events	Up to Day 78

Secondary Outcome Measures

Name	Time	Method
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 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
Change from baseline in Pulse Pressure (PP)	Baseline to Day 4
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 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 to 24 hours postdose, 24 hours to 48 hours postdose, 48 hours to 72 hours postdose	Baseline 24-hour mean SBP is measured from 0 to 24 hours pre-dose
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
Maximum change from baseline in PP across the first 24 hours postdose	Baseline to Day 2 (24-hours post dose)
Change from baseline in Heart Rate (HR)	Up to Day 78
Maximum change from baseline in SBP across the first 24 hours postdose	Baseline to Day 2 (24-hours post dose)
Change from baseline in Stroke Volume (SV)	Baseline to Day 4
Maximum change from baseline in DBP across the first 24 hours postdose	Baseline to Day 2 (24-hours post dose)
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 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
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 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
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 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
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

Trial Locations

Locations (2)

Universitair Ziekenhuis Leuven Gasthuisberg Campus; 🇧🇪 Leuven, Belgium

Ghent University; 🇧🇪 Ghent, Belgium