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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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

Other trials in Moldova

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 groups in NCT05353166
Study groupRoleWhat they receive
Group AExperimentalRandomized 1:1; limited to participants with heart failure with reduced ejection fraction (HFrEF) not taking sacubitril/valsartan
Receives: Drug: REGN5381; Drug: Matching Placebo
Group BExperimentalRandomized 1:1; limited to participants with HFrEF taking sacubitril/valsartan
Receives: Drug: REGN5381; Drug: Matching Placebo
Group CExperimentalRandomized 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.

  1. 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)

  1. 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)

  2. 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)

  3. 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)

  4. 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)

  5. 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)

  6. 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)

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. Peak Concentration (Cmax) of REGN5381 in Serum

    Measured: Up to Day 126

  13. 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

  14. 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.

  1. First posted29 Apr 2022
  2. Study start30 Jun 2022
  3. Primary completion2 Jun 2025
  4. Study completion2 Jun 2025

Resources

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)
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
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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing REGN5381 in people with Heart Failure, run by Regeneron Pharmaceuticals at 1 site in Moldova.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Moldova. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment-emergent Adverse Events (TEAEs) (time frame: From first dose (Day 1) up to end of study (Day 126)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05353166.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2026.

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