Safety and Tolerability of Single Ascending Intravenous (IV) Doses of REGN5381 in Adult Heart Failure Patients With Elevated Pulmonary Capillary Wedge Pressure and Reduced Left Ventricular Ejection Fraction
Study Details
Study Description
Brief Summary
The primary objective of the study is to evaluate the safety and tolerability of single doses of REGN5381 in patients with heart failure and reduced left ventricular ejection fraction (LVEF) with evidence of congestion
The secondary objectives of the study are to:
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Evaluate the effects of single doses of REGN5381 on hemodynamic parameters
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Evaluate the effects of REGN5381 on a clinical biomarker of heart failure severity
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Characterize the pharmacokinetics (PK) of single doses of REGN5381
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Assess the immunogenicity of REGN5381
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: REGN5381 Single dose administered via intravenous (IV) infusion |
Drug: REGN5381
Single dose administered via IV infusion
Drug: Placebo
Single dose administered via IV infusion
|
| Experimental: Placebo Single dose administered via IV infusion |
Drug: REGN5381
Single dose administered via IV infusion
Drug: Placebo
Single dose administered via IV infusion
|
Outcome Measures
Primary Outcome Measures
- Incidence and severity of treatment-emergent adverse events (TEAEs) [Through the end-of-study (EOS) visit up to 78 days post-dose]
Secondary Outcome Measures
- Change from baseline in pulmonary capillary wedge pressure (PCWP) [Over 6 hours post-dose administration]
- Change from baseline right atrial pressure (RAP) [Over 6 hours post-dose administration]
- Change from baseline cardiac output (CO) [Over 6 hours post-dose administration]
- Change from baseline systemic vascular resistance (SVR) [Over 6 hours post-dose administration]
- Change from baseline mean pulmonary artery pressure (mPAP) [Over 6 hours post-dose administration]
- Change from baseline pulmonary vascular resistance (PVR) [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 78 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 78 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 78 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 78 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 78 days post-dose]
- Concentrations of REGN5381 in serum [Through the EOS visit, up to 78 days post-dose]
- Immunogenicity, as measured by anti-drug antibodies (ADA) to REGN5381 [Through the EOS visit, up to 78 days post-dose]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Body mass index (BMI) between 18 and 35 kg/m2, inclusive, rounded to the nearest whole number
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Ambulatory patients with New York Heart Association (NYHA) class II/III heart failure and symptoms of congestion (eg, dyspnea on exertion)
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Left ventricular ejection fraction (LVEF) <50% on echocardiogram within 6 months prior to randomization
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NT-proBNP >300 pg/mL or Brain Natriuretic Peptide (active form) (BNP) >125 pg/mL as described in the protocol within 30 days prior to randomization measured by the local laboratory
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Pulmonary capillary wedge pressure (PCWP) ≥15 mmHg on right heart catheterization (RHC) the morning of anticipated study drug dose administration
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Systolic blood pressure (SBP) ≥100 mmHg at the screening visit and on day -1
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Hematocrit >30% at the screening visit and day -1
Key Exclusion Criteria:
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Currently taking IV vasodilators and/or inotropes
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Taking ENTRESTO (valsartan/sacubitril), 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 ENTRESTO, a PDE inhibitor, or a SGCS at any point during the study
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More than moderate valvular regurgitation/stenosis on echocardiogram within 6 months prior to randomization
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Known infiltrative or hypertrophic cardiomyopathy
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Acute coronary syndrome within prior 6 months of randomization
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History of cardiac arrest
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Cardiac surgery within 3 months of randomization
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Pacemaker or defibrillator placement within prior 30 days of randomization
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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)
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Pulmonary arterial hypertension (World Health Organization [WHO] Group 1)
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Congenital heart disease (repaired or unrepaired)
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Inability to lie flat for cardiac catheterization
Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ARENSIA Exploratory Medicine at the Republican Clinical Hospital | Chișinău | Moldova, Republic of | 2025 |
Sponsors and Collaborators
- Regeneron Pharmaceuticals
Investigators
- Study Director: Clinical Trial Management, Regeneron Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- R5381-HF-2159
- 2021-006337-19