REGN5381 in Adult Participants With Uncontrolled Hypertension (NATRIX-SBP)

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of a Multiple Dose Regimen of REGN5381, an NPR1 Monoclonal Antibody Agonist, in Participants With Uncontrolled Hypertension

This study is researching an experimental drug called REGN5381 (called "study drug"). The study is focused on uncontrolled hypertension (high blood pressure despite being on one or more antihypertensive drugs).

The aim of the study is to see how effective the study drug is in reducing blood pressure. The study is designed as a 2-part study with participants initially enrolling in Part A. Part B of the study will commence and enroll the remaining study participants.

The study is looking at several other research questions, including:

• What side effects may happen from taking the study drug
• How much study drug is in the blood at different times
• Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)

Study Overview

• Status: Terminated
• Conditions: Uncontrolled Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: REGN5381

Detailed Description

As of October 15, 2025, this study has been terminated, and all future onsite visits have been canceled. However, participants have been asked to report safety information to the trial helpline until January 15, 2026.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Bury, United Kingdom, BL9 8RS
    • Protas, Car Park of Asda Pilsworth Road
  • Liverpool
    • Huyton, Liverpool, United Kingdom, L36 7TX
      • Protas, Car Park of Asda Huyton Supercentre
  • Manchester
    • Salford, Manchester, United Kingdom, M3 5GS
      • Protas, Two New Bailey Square

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Adults with SBP ≥130 mm Hg and SBP ≤180 mm Hg at both screening and randomization visit, as described in the protocol
2. ≥ 40 and ≤85 years on a stable regimen of ≥1 anti-hypertensive therapy for at least 1 month at the time of screening or ≥30 and <40 years on a stable regimen of ≥3 anti-hypertensive therapies for at least 1 month at the time of screening

Key Exclusion Criteria

1. Heart rate >100 bpm as described in the protocol
2. Body mass index >45 kg/m2 as described in the protocol
3. Glomerular filtration rate (GFR) <30 mL/min/1.73m2 at screening as described in the protocol
4. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≥3x upper limit of normal (ULN) as described in the protocol

NOTE: Other protocol-defined Inclusion/Exclusion Criteria apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: REGN5381 Low Dose; Randomized as described in the protocol	Drug: REGN5381; Administered per the protocol
Experimental: REGN5381 High Dose; Randomized as described in the protocol	Drug: REGN5381; Administered per the protocol
Placebo Comparator: Placebo; Randomized as described in the protocol	Drug: Placebo; Administered per the protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Unattended Automated Office-Based Blood Pressure (AOBP) Systolic Blood Pressure (SBP)	At week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Unattended AOBP SBP in stage 3 Chronic Kidney Disease (CKD) participants	At week 12
Unattended AOBP SBP in participants on ≥3 anti-hypertensive therapies	At week 12
Time-weighted average AOBP SBP	Through week 12
Time-weighted average AOBP Diastolic Blood Pressure (DBP)	Through week 12
AOBP SBP	From baseline to weeks 2, 4 and 8
AOBP DBP	From baseline to weeks 2, 4, 8 and 12
Mean SBP by 24-hour Ambulatory Blood Pressure Monitoring (ABPM)	At week 12
Concentrations of REGN5381 in serum	Through week 20
Occurrence of Treatment Emergent Adverse Events (TEAEs)	Up to week 23
Severity of TEAEs	Up to week 23
Occurrence of TEAEs leading to discontinuation of study drug	Up to week 23
Occurrence of Anti-Drug Antibodies (ADAs) to REGN5381	Through week 20
Titer of ADAs to REGN5381	Through week 20

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2025
• Primary Completion (Actual): October 15, 2025
• Study Completion (Actual): October 15, 2025

Study Registration Dates

• First Submitted: February 12, 2025
• First Submitted That Met QC Criteria: February 12, 2025
• First Posted (Actual): February 18, 2025

Study Record Updates

• Last Update Posted (Estimated): October 23, 2025
• Last Update Submitted That Met QC Criteria: October 21, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: High blood pressure; Systolic Blood Pressure (SBP)
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: R5381-UHTN-2410

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 or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• 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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes