A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of REGN9035 in Healthy Adult Volunteers and Mildly Hypertensive Participants

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: REGN9035; Other: Placebo; Drug: REGN5381

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, B-3000
    • Universitair Ziekenhuis Leuven Gasthuisberg Campus
• Germany
  • Berlin, Germany, 10117
    • Charité Research Organisation GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

1. Body mass index (BMI) between 18 and 32 kg/m2, inclusive, at the screening visit.
2. Normal or mildly elevated blood pressure as defined in the protocol.

Key Exclusion Criteria:

1. History of unexplained syncope or autonomic dysfunction.
2. History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, or neurological disease.
3. Protocol-defined risk factors for cardiovascular disease.

Note: Other protocol defined 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: Part A; Single ascending dose (SAD) of REGN9035 or matching placebo given by intravenous (IV) administration.	Drug: REGN9035; Part A: Single dose administered by IV infusion on day 1. Part B: Selected doses administered by IV infusion on day 2 or 22.; Other: Placebo; 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.
Experimental: Part B; 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; Part A: Single dose administered by IV infusion on day 1. Part B: Selected doses administered by IV infusion on day 2 or 22.; Other: Placebo; 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.; Drug: REGN5381; Part B: Selected doses administered by IV infusion on day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2022
• Primary Completion (Actual): April 2, 2024
• Study Completion (Actual): April 2, 2024

Study Registration Dates

• First Submitted: February 28, 2022
• First Submitted That Met QC Criteria: March 21, 2022
• First Posted (Actual): March 22, 2022

Study Record Updates

• Last Update Posted (Actual): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Healthy Volunteers; High Blood Pressure; Mild Hypertension
• Other Study ID Numbers: R9035-HV-2125; 2021-005174-26 (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: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; 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
• product manufactured in and exported from the U.S.: Yes