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

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05353166
• Other study ID #: R5381-HF-2159
• Secondary ID: 2021-006337-1920
• Status: Recruiting
• Phase: Phase 2
• Start date: June 30, 2022
• Est. completion date: April 30, 2025

Study information

• Verified date: February 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 122
• Est. completion date: April 30, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• REGN5381
Single dose administered via IV infusion
• Matching Placebo
Single dose administered via IV infusion

Locations

Country	Name	City	State
Belgium	ZOL Genk	Genk	Limburg
Belgium	Universitaire Ziekenhuizen (UZ) Leuven - Campus Gasthuisberg	Leuven	Flemish Brabant
Hungary	Gottsegen National Cardiovascular Center	Budapest	Pest
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont	Budapest	Pest
Moldova, Republic of	ARENSIA Exploratory Medicine at the Republican Clinical Hospital	Chi?inau
Poland	Klinika Kardiologii	Bialystok	Podlasie
Poland	Gornoslaskie Centrum Medyczne Szpital W Ochojcu	Katowice
Poland	Bieganski Hospital	Lodz	Lodz Voivodeship
Poland	Central Clinical Hospital	Lodz
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego	Wroclaw	Dolny Slask
Romania	Arensia Monza Medical Center	Bucharest
Turkey	Dokuz Eylul University Medical Faculty	Izmir

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

Belgium,  Hungary,  Moldova, Republic of,  Poland,  Romania,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of treatment-emergent adverse events (TEAEs)		Through the end-of-study (EOS) visit up to 126 days post-dose
Secondary	Change from baseline in pulmonary capillary wedge pressure (PCWP)	In cohorts undergoing right heart catheterization	Over 6 hours post-dose administration
Secondary	Change from baseline right atrial pressure (RAP)	In cohorts undergoing right heart catheterization	Over 6 hours post-dose administration
Secondary	Change from baseline cardiac output (CO)	In cohorts undergoing right heart catheterization	Over 6 hours post-dose administration
Secondary	Change from baseline systemic vascular resistance (SVR)	In cohorts undergoing right heart catheterization	Over 6 hours post-dose administration
Secondary	Change from baseline mean pulmonary artery pressure (mPAP)	In cohorts undergoing right heart catheterization	Over 6 hours post-dose administration
Secondary	Change from baseline pulmonary vascular resistance (PVR)	In cohorts undergoing right heart catheterization	Over 6 hours post-dose administration
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Concentrations of REGN5381 in serum		Through the EOS visit, up to 126 days post-dose
Secondary	Immunogenicity, as measured by anti-drug antibodies (ADA) to REGN5381		Through the EOS visit, up to 126 days post-dose