Heart FailurePhase 2NCT05353166
REGN5381 in Heart Failure Adult Participants With Elevated Pulmonary Capillary Wedge Pressure
A Phase 2 study testing REGN5381 in people with Heart Failure, run by Regeneron Pharmaceuticals at 1 site in Moldova.
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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- REGN5381
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 59 participants
- Where
- 1 siteMoldova
- Study dates
- 30 Jun 2022to 2 Jun 2025
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Body mass index (BMI) between 18 and 35 kg/m^2, inclusive, rounded to the nearest whole number
- 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.)
- 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).
- Participants who, in the opinion of the investigator, require a right heart catheterization (not applicable for HFrEF patients not taking sacubitril/valsartan [Group A]).
- Left ventricular ejection fraction (LVEF) ≥50% on echocardiogram (ie, HFpEF participants) within 90 days prior to randomization (only for HFpEF participants in Group C)
- 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]).
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- 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).
- Systolic blood pressure (SBP) ≥110 mmHg at the screening visit and on day -1
- Hematocrit >30% at the screening visit and day -1
Who cannot join
- Currently taking IV vasodilators and/or inotropes
- Taking sacubitril/valsartan (only for HFrEF and HFpEF participants not taking sacubitril/valsartan [Group A and Group C, respectively])
- 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
- More than moderate valvular regurgitation/stenosis (ie, moderate-to-severe or severe) on echocardiogram within 90 days prior to randomization
- Known infiltrative or hypertrophic cardiomyopathy
- Acute coronary syndrome within prior 6 months of randomization
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- History of cardiac arrest
- Cardiac surgery within 3 months of randomization
- Pacemaker or defibrillator placement within prior 30 days of randomization
- 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)
- 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
- Congenital heart disease (repaired or unrepaired)
- Inability to lie flat for cardiac catheterization
- Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
Trial locations and contacts
1 site in 1 country.
Moldova1 site
ARENSIA Exploratory Medicine at the Republican Clinical Hospital
Chisinau, 2025
About this study
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
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)
Read the detailed description
Note: Group A has stopped enrolling and Group B will not enroll participants
- Conditions
- Heart Failure
- Being tested
- REGN5381, Matching Placebo
- Keywords
- New York Heart Association (NYHA) class II/III with symptoms of congestion, Elevated Pulmonary Capillary Wedge Pressure, Reduced Left Ventricular Ejection Fraction
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
REGN5381Drug
Single dose administered via IV infusion
Matching PlaceboDrug
Single dose administered via IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Randomized 1:1; limited to participants with heart failure with reduced ejection fraction (HFrEF) not taking sacubitril/valsartan Receives: Drug: REGN5381; Drug: Matching Placebo |
| Group B | Experimental | Randomized 1:1; limited to participants with HFrEF taking sacubitril/valsartan Receives: Drug: REGN5381; Drug: Matching Placebo |
| Group C | Experimental | Randomized 1:1; limited to participants with heart failure with preserved ejection fraction (HFpEF) not taking sacubitril/valsartan Receives: Drug: REGN5381; Drug: Matching Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as those adverse events with either initial onset after study drug dose or that represented an exacerbation of a pre-existing condition after the study drug dose.
Measured: From first dose (Day 1) up to end of study (Day 126)
Secondary outcomes (14)
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP)
PCWP was collected during the right heart catheterization on Day 1.
Measured: Baseline, Day 1 (2 hours, 4 hours, and 6 hours post end of infusion)
Change From Baseline in Central Venous Pressure (CVP)
CVP was collected during the right heart catheterization on day 1. For Group A 10mg cohort, the bedside monitor at the site was not compatible with the invasive hemodynamic measurement device, therefore CVP was not captured.
Measured: Baseline, Day 1 (0-1 hour, 1-2 hours, 2-3 hours, 3-4 hours, 4-5 hours, 5-6 hours, and 6-7 hours post start of infusion)
Change From Baseline in Invasive Cardiac Output (CO)
CO was collected during the right heart catheterization on day 1. For Group A 10mg cohort, the bedside monitor at the site was not compatible with the invasive hemodynamic measurement device, therefore CO was not captured.
Measured: Baseline, Day 1 (0-1 hour, 1-2 hours, 2-3 hours, 3-4 hours, 4-5 hours, 5-6 hours, and 6-7 hours post start of infusion)
Change From Baseline in Systemic Vascular Resistance (SVR)
SVR was derived as follows: [(Mean Arterial Pressure-Central Venous Pressure)*80]/ Invasive Cardiac Output. For the Group A: 10 mg cohort, the site's bedside monitor was not compatible with the invasive hemodynamic measurement device. As a result, CVP was not captured, and SVR could not be calculated due to the missing CVP data.
Measured: Baseline, Day 1 (0 hours, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, and 6 hours post end of infusion)
Change From Baseline in Mean Pulmonary Artery Pressure (mPAP)
mPAP was collected during the right heart catheterization on day 1.
Measured: Baseline, Day 1 (0-1 hour, 1-2 hours, 2-3 hours, 3-4 hours, 4-5 hours, 5-6 hours, and 6-7 hours post start of infusion)
Change From Baseline in Pulmonary Vascular Resistance (PVR)
Pulmonary Vascular Resistance was derived as follows: [(Mean Pulmonary Artery Pressure-Pulmonary Capillary Wedge Pressure)*80]/ Invasive Cardiac Output.
Measured: Baseline, Day 1 (2 hours, 4 hours, and 6 hours post end of infusion)
Change From Baseline in Systolic Blood Pressure (SBP)
For participants enrolled in Group A cohorts, blood pressure was initially assessed every 2 hours for up to 6 hours after the end of infusion. Following implementation of Protocol Amendment 3, the assessment frequency was increased to hourly only for participants undergoing right heart catheterization (RHC).
Measured: Baseline, Day 1 (0, 1, 2, 3, 4, 5, 6, 7, 8 hours post end of infusion), Day 2 to Day 5 every 8 hours, Day 6 first 8 hours, Day 8, Day 15, Day 22, Day 36, Day 57, Day 78, Day 99, Day 126
Change From Baseline in Diastolic Blood Pressure (DBP)
For participants enrolled in Group A cohorts, blood pressure was initially assessed every 2 hours for up to 6 hours after the end of infusion. Following implementation of Protocol Amendment 3, the assessment frequency was increased to hourly only for participants undergoing RHC.
Measured: Baseline, Day 1 (0, 1, 2, 3, 4, 5, 6, 7, 8 hours post end of infusion), Day 2 to Day 5 every 8 hours, Day 6 first 8 hours, Day 8, Day 15, Day 22, Day 36, Day 57, Day 78, Day 99, Day 126
Change From Baseline in Mean Arterial Pressure (MAP)
MAP was derived as follows: (1/3*SBP + 2/3*DBP).
Measured: Baseline, Day 1 (2 hours, 4 hours, and 6 hours post end of infusion), Day 2 (first 8 hours, second 8 hours, third 8 hours), Day 3 (first 8 hours, second 8 hours, third 8 hours), Day 8, Day 15, Day 22, Day 36, Day 57, Day 78, Day 99, Day 126
Change From Baseline in Pulse Rate (PR)
For participants enrolled in Group A cohorts, pulse rate was initially assessed every 2 hours for up to 6 hours after the end of infusion. Following implementation of Protocol Amendment 3, the assessment frequency was increased to hourly only for participants undergoing RHC.
Measured: Baseline, Day 1 (2 hours, 4 hours, and 6 hours post end of infusion), Day 2 (first 8 hours, second 8 hours, third 8 hours), Day 3 (first 8 hours, second 8 hours, third 8 hours), Day 8, Day 15, Day 22, Day 36, Day 57, Day 78, Day 99, Day 126
Fold Change From Baseline in N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP)
NT-proBNP is a clinical biomarker of heart failure. Coefficient of Variation for Fold Change from Baseline was computed as (standard deviation of the natural log-scale of the respective variable) *100. Fold Change from Baseline is the ratio of Post-Baseline to Baseline, and it is assumed to follow a lognormal distribution. Per the study design, only some participants had a Day 4/Day 5 visit. Therefore, NT-proBNP data were not collected at this time point for all participants.
Measured: Baseline, Day 1 (2 hours, 4 hours, and 6 hours post end of infusion), Day 2 (24 hours post end of infusion), Day 3, Day 4, Day 5, Day 8, Day 15, Day 22, Day 36, Day 57, Day 78, Day 99, Day 126
Peak Concentration (Cmax) of REGN5381 in Serum
Measured: Up to Day 126
Area Under the Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUClast) of REGN5381 in Serum
Measured: Up to Day 126
Number of Participants With Anti-drug Antibodies (ADA)
The ADA status of each participant was classified as one of the following:
- Negative - If all samples were found to be negative in the ADA assay
- Pre-existing immunoreactivity - If the baseline sample was positive and all post baseline ADA titers were reported as less than 9-fold the baseline titer value
- Treatment-Boosted Response
- Treatment-Emergent Response
Measured: Baseline up to Day 126
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2022
- Study start30 Jun 2022
- Primary completion2 Jun 2025
- Study completion2 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Regeneron PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Management, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05353166
- Sponsor's protocol ID
- R5381-HF-2159
- Other IDs
- 2021-006337-19, 2023-506674-13-00, 2023
- Status last verified
- Sep 2026
- First submitted
- 25 Apr 2022
- Last updated
- 29 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing