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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: REGN5381; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • Ghent University
  • Leuven, Belgium, B-3000
    • Universitair Ziekenhuis Leuven Gasthuisberg Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: REGN5381; Single dose REGN5381 administered via IV infusion	Drug: REGN5381; Single dose REGN5381 administered via IV infusion
Other: Placebo; Placebo matching single dose REGN 5381 administered via IV infusion	Other: Placebo; Placebo matching single dose REGN 5381 administered via IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Actual): December 14, 2022
• Study Completion (Actual): December 14, 2022

Study Registration Dates

• First Submitted: July 28, 2020
• First Submitted That Met QC Criteria: August 7, 2020
• First Posted (Actual): August 10, 2020

Study Record Updates

• Last Update Posted (Actual): December 20, 2022
• Last Update Submitted That Met QC Criteria: December 19, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Normal Blood Pressure (BP); Mildly Elevated BP
• Other Study ID Numbers: R5381-HV-1987; 2020-000940-75 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• IPD Sharing Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., Food and Drug Administration (FDA), European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No