Clinical trial NCT04506645: Study to Assess the Safety, Tolerability, and Pharmacokinetics of REGN5381 (an NPR1 Agonist) in Adult Humans
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Normal Blood Pressure (BP)
Mildly Elevated BP
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-08-10
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Up to Day 78
Secondary outcomes:
measure: Change from baseline in Systolic Blood Pressure (SBP)
timeFrame: Up to Day 78
measure: Change from baseline in Diastolic Blood Pressure (DBP)
timeFrame: Up to Day 78
measure: Change from baseline in Mean Arterial Pressure (MAP)
timeFrame: Baseline to Day 4
measure: Change from baseline in Pulse Pressure (PP)
timeFrame: Baseline to Day 4
measure: Change from baseline in Heart Rate (HR)
timeFrame: Up to Day 78
measure: Change from baseline in Stroke Volume (SV)
timeFrame: Baseline to Day 4
measure: Maximum change from baseline in SBP across the first 24 hours postdose
timeFrame: Baseline to Day 2 (24-hours post dose)
measure: Maximum change from baseline in DBP across the first 24 hours postdose
timeFrame: Baseline to Day 2 (24-hours post dose)
measure: Maximum change from baseline in MAP across the first 24 hours postdose
timeFrame: Baseline to Day 2 (24-hours post dose)
measure: Maximum change from baseline in PP across the first 24 hours postdose
timeFrame: Baseline to Day 2 (24-hours post dose)
measure: Maximum change from baseline in HR across the first 24 hours postdose
timeFrame: Baseline to Day 2 (24-hours post dose)
measure: Maximum change from baseline in SV across the first 24 hours postdose
timeFrame: Baseline to Day 2 (24-hours post dose)
measure: 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
timeFrame: Baseline to 24 hours postdose, 24 hours to 48 hours postdose, 48 hours to 72 hours postdose
measure: 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
timeFrame: Baseline to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose
measure: 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
timeFrame: Baseline to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose
measure: 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
timeFrame: Baseline to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose
measure: 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
timeFrame: Baseline to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose
measure: Concentrations of REGN5381 over time
timeFrame: Up to Day 78
measure: Number of subjects who develop anti-drug antibodies (ADA) and titers
timeFrame: Up to Day 78
measure: Percentage of subjects who develop anti-drug antibodies (ADA) and titers
timeFrame: Up to Day 78
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Ghent University
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven Gasthuisberg Campus
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: