REGN5381 in Adult Participants With Uncontrolled Hypertension

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)

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.

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