REGN5381 in Heart Failure Adult Participants With Elevated Pulmonary Capillary Wedge Pressure

A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of REGN5381, an NPR1 Agonist, in Heart Failure Patients With Elevated Pulmonary Capillary Wedge Pressure

This study is researching an experimental drug called REGN5381, further referred to as study drug. The study is focused on adult participants with heart failure that, in the opinion of the study doctor, have a clinical indication for right heart catheterization (RHC). The aim of the study is to evaluate the safety and tolerability of the study drug.

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: Recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Drug: REGN5381; Drug: Matching Placebo

Detailed Description

Note: Group A has stopped enrolling and Group B will not enroll participants

• Study Type: Interventional
• Enrollment (Estimated): 122
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• Belgium
  • Flemish Brabant
    • Leuven, Flemish Brabant, Belgium, 3000
      • Withdrawn
      • Universitaire Ziekenhuizen (UZ) Leuven - Campus Gasthuisberg
  • Limburg
    • Genk, Limburg, Belgium, 3600
      • Withdrawn
      • ZOL Genk
• Hungary
  • Pest
    • Budapest, Pest, Hungary, 1096
      • Withdrawn
      • Gottsegen National Cardiovascular Center
    • Budapest, Pest, Hungary, 1134
      • Withdrawn
      • Magyar Honvedseg Egeszsegugyi Kozpont
• Moldova, Republic of
  • Chișinău, Moldova, Republic of, 2025
    • Recruiting
    • ARENSIA Exploratory Medicine at the Republican Clinical Hospital
• Poland
  • Katowice, Poland, 40-635
    • Withdrawn
    • Gornoslaskie Centrum Medyczne Szpital W Ochojcu
  • Lodz, Poland, 92-213
    • Withdrawn
    • Central Clinical Hospital
  • Dolny Śląsk
    • Wrocław, Dolny Śląsk, Poland, 50-556
      • Withdrawn
      • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego
  • Lodz Voivodeship
    • Lodz, Lodz Voivodeship, Poland, 91-347
      • Withdrawn
      • Bieganski Hospital
  • Podlasie
    • Białystok, Podlasie, Poland, 15-276
      • Withdrawn
      • Klinika Kardiologii
• Romania
  • Bucharest, Romania, 011658
    • Withdrawn
    • Arensia Monza Medical Center
• Turkey
  • Izmir, Turkey, 35340
    • Withdrawn
    • Dokuz Eylul University Medical Faculty

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Body mass index (BMI) between 18 and 35 kg/m^2, inclusive, rounded to the nearest whole number
2. Ambulatory participants with New York Heart Association (NYHA) class II/III heart failure and at least 1 sign and/or symptom of congestion (eg, dyspnea on exertion, worsening edema, orthopnea, etc.)
3. Left ventricular ejection fraction (LVEF) ≥20 % and <50% on echocardiogram (ie, HFrEF participants) within 90 days prior to randomization (only for HFrEF participants in Group A and Group B).
4. Participants who, in the opinion of the investigator, require a right heart catheterization (not applicable for HFrEF patients not taking sacubitril/valsartan [Group A]).
5. Left ventricular ejection fraction (LVEF) ≥50% on echocardiogram (ie, HFpEF participants) within 90 days prior to randomization (only for HFpEF participants in Group C)
6. NT-proBNP >1000 pg/mL or Brain Natriuretic Peptide (active form) (BNP) >300 pg/mL as described in the protocol within 30 days prior to randomization measured by the local laboratory (only for HFrEF participants [Group A and Group B]).
7. Pulmonary capillary wedge pressure (PCWP) ≥15 mmHg and right artrial pressure (RAP) >5 mmHg on right heart catheterization (RHC) the morning of anticipated study drug dose administration (not applicable for HFrEF participants not taking sacubitril/valsartan [Group A] as described in the protocol).
8. Systolic blood pressure (SBP) ≥110 mmHg at the screening visit and on day -1
9. Hematocrit >30% at the screening visit and day -1

Key Exclusion Criteria:

1. Currently taking IV vasodilators and/or inotropes
2. Taking sacubitril/valsartan (only for HFrEF and HFpEF participants not taking sacubitril/valsartan [Group A and Group C, respectively])
3. Taking a phosphodiesterase (PDE) inhibitor (eg, sildenafil), or a soluble guanylate cyclase stimulator (SGCS; ie, vericiguat) within 2 weeks of the screening visit or planning on taking valsartan/sacubitril, a PDE inhibitor, or a SGCS at any point during the study
4. More than moderate valvular regurgitation/stenosis (ie, moderate-to-severe or severe) on echocardiogram within 90 days prior to randomization
5. Known infiltrative or hypertrophic cardiomyopathy
6. Acute coronary syndrome within prior 6 months of randomization
7. History of cardiac arrest
8. Cardiac surgery within 3 months of randomization
9. Pacemaker or defibrillator placement within prior 30 days of randomization
10. Severe chronic obstructive pulmonary disease (COPD) (defined as Forced Expiratory Volume in 1st second [FEV1] <50% of predicted or Global Initiative for Chronic Obstructive Lung Disease [GOLD] 3 or 4)
11. Pulmonary arterial hypertension (World Health Organization [WHO] Group 1) and any medical history at any time of more than moderate pulmonary hypertension (ie, moderate-to-severe, or severe pulmonary hypertension, as described in the protocol
12. Congenital heart disease (repaired or unrepaired)
13. Inability to lie flat for cardiac catheterization

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: Group A; Randomized 1:1; limited to participants with heart failure with reduced ejection fraction (HFrEF) not taking sacubitril/valsartan	Drug: REGN5381; Single dose administered via IV infusion; Drug: Matching Placebo; Single dose administered via IV infusion
Experimental: Group B; Randomized 1:1; limited to participants with HFrEF taking sacubitril/valsartan	Drug: REGN5381; Single dose administered via IV infusion; Drug: Matching Placebo; Single dose administered via IV infusion
Experimental: Group C; Randomized 1:1; limited to participants with heart failure with preserved ejection fraction (HFpEF) not taking sacubitril/valsartan	Drug: REGN5381; Single dose administered via IV infusion; Drug: Matching Placebo; Single dose administered via IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and severity of treatment-emergent adverse events (TEAEs)	Through the end-of-study (EOS) visit up to 126 days post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in pulmonary capillary wedge pressure (PCWP)	In cohorts undergoing right heart catheterization	Over 6 hours post-dose administration
Change from baseline right atrial pressure (RAP)	In cohorts undergoing right heart catheterization	Over 6 hours post-dose administration
Change from baseline cardiac output (CO)	In cohorts undergoing right heart catheterization	Over 6 hours post-dose administration
Change from baseline systemic vascular resistance (SVR)	In cohorts undergoing right heart catheterization	Over 6 hours post-dose administration
Change from baseline mean pulmonary artery pressure (mPAP)	In cohorts undergoing right heart catheterization	Over 6 hours post-dose administration
Change from baseline pulmonary vascular resistance (PVR)	In cohorts undergoing right heart catheterization	Over 6 hours post-dose administration
Change from baseline in systolic blood pressure (SBP)		Over the first 6 hours, 24 hours post-dose administration (day 1), through the EOS visit up to 126 days post-dose
Change from baseline in diastolic blood pressure (DBP)		Over the first 6 hours, 24 hours post-dose administration (day 1), through the EOS visit up to 126 days post-dose
Change from baseline in mean arterial pressure (MAP)		Over the first 6 hours, 24 hours post-dose administration (day 1), through the EOS visit up to 126 days post-dose
Change from baseline in pulse rate (PR)		Over the first 6 hours, 24 hours post-dose administration (day 1), through the EOS visit up to 126 days post-dose
Change from baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP)		To 6 hours, 24 hours post-dose administration (day 1), through the EOS visit up to 126 days post-dose
Concentrations of REGN5381 in serum		Through the EOS visit, up to 126 days post-dose
Immunogenicity, as measured by anti-drug antibodies (ADA) to REGN5381		Through the EOS visit, up to 126 days post-dose

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2022
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): April 30, 2025

Study Registration Dates

• First Submitted: April 25, 2022
• First Submitted That Met QC Criteria: April 25, 2022
• First Posted (Actual): April 29, 2022

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Elevated Pulmonary Capillary Wedge Pressure; Reduced Left Ventricular Ejection Fraction; New York Heart Association (NYHA) class II/III with symptoms of congestion
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: R5381-HF-2159; 2021-006337-19 (EudraCT Number); 2023-506674-13-00 (Other Identifier: EUCT 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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes