Clinical trial NCT05353166: REGN5381 in Heart Failure Adult Participants With Elevated Pulmonary Capillary Wedge Pressure
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Keywords: New York Heart Association (NYHA) class II/III with symptoms of congestion
Elevated Pulmonary Capillary Wedge Pressure
Reduced Left Ventricular Ejection Fraction
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-04-29
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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)

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

Eligibility criteria: 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

Primary outcomes:
measure: Incidence and severity of treatment-emergent adverse events (TEAEs)
timeFrame: Through the end-of-study (EOS) visit up to 126 days post-dose
Secondary outcomes:
measure: Change from baseline in pulmonary capillary wedge pressure (PCWP)
timeFrame: Over 6 hours post-dose administration
measure: Change from baseline right atrial pressure (RAP)
timeFrame: Over 6 hours post-dose administration
measure: Change from baseline cardiac output (CO)
timeFrame: Over 6 hours post-dose administration
measure: Change from baseline systemic vascular resistance (SVR)
timeFrame: Over 6 hours post-dose administration
measure: Change from baseline mean pulmonary artery pressure (mPAP)
timeFrame: Over 6 hours post-dose administration
measure: Change from baseline pulmonary vascular resistance (PVR)
timeFrame: Over 6 hours post-dose administration
measure: Change from baseline in systolic blood pressure (SBP)
timeFrame: Over the first 6 hours, 24 hours post-dose administration (day 1), through the EOS visit up to 126 days post-dose
measure: Change from baseline in diastolic blood pressure (DBP)
timeFrame: Over the first 6 hours, 24 hours post-dose administration (day 1), through the EOS visit up to 126 days post-dose
measure: Change from baseline in mean arterial pressure (MAP)
timeFrame: Over the first 6 hours, 24 hours post-dose administration (day 1), through the EOS visit up to 126 days post-dose
measure: Change from baseline in pulse rate (PR)
timeFrame: Over the first 6 hours, 24 hours post-dose administration (day 1), through the EOS visit up to 126 days post-dose
measure: Change from baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP)
timeFrame: To 6 hours, 24 hours post-dose administration (day 1), through the EOS visit up to 126 days post-dose
measure: Concentrations of REGN5381 in serum
timeFrame: Through the EOS visit, up to 126 days post-dose
measure: Immunogenicity, as measured by anti-drug antibodies (ADA) to REGN5381
timeFrame: Through the EOS visit, up to 126 days post-dose
Other outcomes:
Locations:
city: Chișinău
country: Moldova, Republic of
facility: ARENSIA Exploratory Medicine at the Republican Clinical Hospital
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: