<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04506645</url>
  </required_header>
  <id_info>
    <org_study_id>R5381-HV-1987</org_study_id>
    <secondary_id>2020-000940-75</secondary_id>
    <nct_id>NCT04506645</nct_id>
  </id_info>
  <brief_title>Study to Assess the Safety, Tolerability, and Pharmacokinetics of REGN5381 (an NPR1 Agonist) in Adult Humans</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Regeneron Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Regeneron Pharmaceuticals</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of the study is to evaluate the safety and tolerability of single&#xD;
      intravenous (IV) doses of REGN5381 in healthy normotensive and otherwise healthy hypertensive&#xD;
      adults.&#xD;
&#xD;
      The secondary objectives of the study are:&#xD;
&#xD;
        -  To evaluate the effect of single IV doses of REGN5381 on blood pressure (BP) and heart&#xD;
           rate (HR) in healthy normotensive and otherwise healthy hypertensive adults&#xD;
&#xD;
        -  To evaluate the effect of single IV doses of REGN5381 on cardiac stroke volume (SV)&#xD;
&#xD;
        -  To evaluate the pharmacokinetics (PK) of single IV doses of REGN5381&#xD;
&#xD;
        -  To evaluate the immunogenicity of single IV doses of REGN5381&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2020</start_date>
  <completion_date type="Actual">December 14, 2022</completion_date>
  <primary_completion_date type="Actual">December 14, 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events</measure>
    <time_frame>Up to Day 78</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Systolic Blood Pressure (SBP)</measure>
    <time_frame>Up to Day 78</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Diastolic Blood Pressure (DBP)</measure>
    <time_frame>Up to Day 78</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Mean Arterial Pressure (MAP)</measure>
    <time_frame>Baseline to Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Pulse Pressure (PP)</measure>
    <time_frame>Baseline to Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Heart Rate (HR)</measure>
    <time_frame>Up to Day 78</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Stroke Volume (SV)</measure>
    <time_frame>Baseline to Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum change from baseline in SBP across the first 24 hours postdose</measure>
    <time_frame>Baseline to Day 2 (24-hours post dose)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum change from baseline in DBP across the first 24 hours postdose</measure>
    <time_frame>Baseline to Day 2 (24-hours post dose)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum change from baseline in MAP across the first 24 hours postdose</measure>
    <time_frame>Baseline to Day 2 (24-hours post dose)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum change from baseline in PP across the first 24 hours postdose</measure>
    <time_frame>Baseline to Day 2 (24-hours post dose)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum change from baseline in HR across the first 24 hours postdose</measure>
    <time_frame>Baseline to Day 2 (24-hours post dose)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum change from baseline in SV across the first 24 hours postdose</measure>
    <time_frame>Baseline to Day 2 (24-hours post dose)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <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</measure>
    <time_frame>Baseline to 24 hours postdose, 24 hours to 48 hours postdose, 48 hours to 72 hours postdose</time_frame>
    <description>Baseline 24-hour mean SBP is measured from 0 to 24 hours pre-dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <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</measure>
    <time_frame>Baseline to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose</time_frame>
    <description>Baseline 24-hour mean DBP is measured from 0 to 24 hours pre-dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <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</measure>
    <time_frame>Baseline to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose</time_frame>
    <description>Baseline 24-hour mean MAP is measured from 0 to 24 hours pre-dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <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</measure>
    <time_frame>Baseline to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose</time_frame>
    <description>Baseline 24-hour mean PP is measured from 0 to 24 hours pre-dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <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</measure>
    <time_frame>Baseline to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose</time_frame>
    <description>Baseline 24-hour mean HR is measured from 0 to 24 hours pre-dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentrations of REGN5381 over time</measure>
    <time_frame>Up to Day 78</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects who develop anti-drug antibodies (ADA) and titers</measure>
    <time_frame>Up to Day 78</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects who develop anti-drug antibodies (ADA) and titers</measure>
    <time_frame>Up to Day 78</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>REGN5381</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose REGN5381 administered via IV infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Placebo matching single dose REGN 5381 administered via IV infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>REGN5381</intervention_name>
    <description>Single dose REGN5381 administered via IV infusion</description>
    <arm_group_label>REGN5381</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo matching single dose REGN 5381 administered via IV infusion</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        1. Normal or mildly elevated blood pressure as defined in the protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of cardiovascular disease as defined in the protocol&#xD;
&#xD;
          2. Protocol-defined risk factors for cardiovascular disease&#xD;
&#xD;
          3. History of unexplained syncope, autonomic dysfunction, or neurologic disease.&#xD;
&#xD;
        NOTE: Additional Inclusion / Exclusion criteria apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trial Management</last_name>
    <role>Study Director</role>
    <affiliation>Regeneron Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ghent University</name>
      <address>
        <city>Ghent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitair Ziekenhuis Leuven Gasthuisberg Campus</name>
      <address>
        <city>Leuven</city>
        <zip>B-3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>July 28, 2020</study_first_submitted>
  <study_first_submitted_qc>August 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2020</study_first_posted>
  <last_update_submitted>December 19, 2022</last_update_submitted>
  <last_update_submitted_qc>December 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Normal Blood Pressure (BP)</keyword>
  <keyword>Mildly Elevated BP</keyword>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_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_time_frame>
    <ipd_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_access_criteria>
    <ipd_url>https://vivli.org/</ipd_url>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04506645
org study id: R5381-HV-1987
secondary id: 2020-000940-75
nct id: NCT04506645
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
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
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Incidence of Treatment-Emergent Adverse Events
time frame: Up to Day 78
measure: Change from baseline in Systolic Blood Pressure (SBP)
time frame: Up to Day 78
measure: Change from baseline in Diastolic Blood Pressure (DBP)
time frame: Up to Day 78
measure: Change from baseline in Mean Arterial Pressure (MAP)
time frame: Baseline to Day 4
measure: Change from baseline in Pulse Pressure (PP)
time frame: Baseline to Day 4
measure: Change from baseline in Heart Rate (HR)
time frame: Up to Day 78
measure: Change from baseline in Stroke Volume (SV)
time frame: Baseline to Day 4
measure: Maximum change from baseline in SBP across the first 24 hours postdose
time frame: Baseline to Day 2 (24-hours post dose)
measure: Maximum change from baseline in DBP across the first 24 hours postdose
time frame: Baseline to Day 2 (24-hours post dose)
measure: Maximum change from baseline in MAP across the first 24 hours postdose
time frame: Baseline to Day 2 (24-hours post dose)
measure: Maximum change from baseline in PP across the first 24 hours postdose
time frame: Baseline to Day 2 (24-hours post dose)
measure: Maximum change from baseline in HR across the first 24 hours postdose
time frame: Baseline to Day 2 (24-hours post dose)
measure: Maximum change from baseline in SV across the first 24 hours postdose
time frame: 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
time frame: Baseline to 24 hours postdose, 24 hours to 48 hours postdose, 48 hours to 72 hours postdose
description: Baseline 24-hour mean SBP is measured from 0 to 24 hours pre-dose
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
time frame: Baseline to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose
description: Baseline 24-hour mean DBP is measured from 0 to 24 hours pre-dose
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
time frame: Baseline to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose
description: Baseline 24-hour mean MAP is measured from 0 to 24 hours pre-dose
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
time frame: Baseline to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose
description: Baseline 24-hour mean PP is measured from 0 to 24 hours pre-dose
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
time frame: Baseline to 24 hours, 24 to 48 hours, and 48 to 72 hours postdose
description: Baseline 24-hour mean HR is measured from 0 to 24 hours pre-dose
measure: Concentrations of REGN5381 over time
time frame: Up to Day 78
measure: Number of subjects who develop anti-drug antibodies (ADA) and titers
time frame: Up to Day 78
measure: Percentage of subjects who develop anti-drug antibodies (ADA) and titers
time frame: Up to Day 78
arm group label: REGN5381
arm group type: Experimental
description: Single dose REGN5381 administered via IV infusion
arm group label: Placebo
arm group type: Other
description: Placebo matching single dose REGN 5381 administered via IV infusion
intervention type: Drug
intervention name: REGN5381
description: Single dose REGN5381 administered via IV infusion
arm group label: REGN5381
intervention type: Other
intervention name: Placebo
description: Placebo matching single dose REGN 5381 administered via IV infusion
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Clinical Trial Management
role: Study Director
affiliation: Regeneron Pharmaceuticals
facility: 
facility: 
country: Belgium
responsible party type: Sponsor
sharing ipd: Yes
ipd description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd 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 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 url: https://vivli.org/