Heart FailurePhase 2NATRIX-BNPNCT06237309
REGN5381 in Adult Participants With Heart Failure With Reduced Ejection Fraction
A Phase 2 study testing REGN5381 in people with Heart Failure, run by Regeneron Pharmaceuticals at 44 sites in 12 countries.
Trial summary
This study is researching an experimental drug called REGN5381 (called "study drug"). The study is focused on patients with heart failure with reduced ejection fraction (ie, the heart is not functioning as well as it should). The aim of the study is to see how safe, tolerable, and effective the study drug is. Read more about this study
- Who is it for?
- Ages 18 years and older
- 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
- 89 participants
- Where
- 44 sitesin 12 countries
- Study dates
- 11 Apr 2024to 29 Dec 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Body mass index (BMI) between 18 and 45 kg/m^2, inclusive, at initial screening visit
- Diagnosis of chronic heart failure
- Left ventricular ejection fraction 20-49% by echocardiogram performed within 3 months of screening
- Plasma NT-proBNP ≥800 pg/mL (or ≥1000 pg/mL if in atrial fibrillation) at screening (visit 1) and NT-proBNP ≥600 pg/mL (or ≥800 pg/mL if in atrial fibrillation) approximately 30 days prior to randomization (visit 5)
- Receiving optimized standard of care therapy for heart failure as described in the protocol
- Sacubitril-valsartan treatment:
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- Treatment with sacubitril-valsartan at screening and at baseline permitted in Part A2 sacubitril-valsartan cohort and in Part B if supported by safety data from the Part A2 sacubitril-valsartan cohort as described in the protocol
- Estimated Glomerular Filtration Rate (eGFR) levels:
- eGFR of ≥30 mL/min/1.73 m2 according to locally used formula (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] preferred), at screening (visit 1) or approximately 30 days prior to randomization (visit 5) as described in the protocol
Who cannot join
- Hospital discharge within 180 days of anticipated randomization
- Resting SBP that remains out of range after two repeated measurements prior to randomization as described in the protocol
- Current or recent diagnosis of acute coronary syndrome or myocardial infarction as described in the protocol
- History of symptomatic autonomic dysfunction as evidenced by orthostatic hypotension and/or syncope
- Unexplained syncope <12 months prior to initial screening or during the Run-in period
- History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, or neurological disease, as assessed by the investigator that may confer unreasonable risk to the participant's participation in the study
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- Uncorrected congenital heart disease
- Cardiac surgery within 6 months prior to screening or any planned surgery during the study
- Implantation of a cardiac resynchronization therapy device in the prior 90 days, or planned during the study, or planned device optimization 30 days prior to randomization or during the study
- Current chronic lung disease requiring long-term oxygen therapy
- Note: Other protocol-defined inclusion/ exclusion criteria apply
Trial locations and contacts
44 sites in 12 countries.
44 sites in 12 countries
Belgium8 sites
Onze Lieve Vrouw Ziekenhuis Aalst
Aalst, Oost-Vlaanderen, 9300
Anima Research Center
Alken, Limburg, 3570
Algemeen Ziekenhuis St Jan Brugge Oostende Av
Bruges, West Flanders, 8000
Grand Hopital de Charleroi
Gilly, Hainaut, 6060
Algemeen Ziekenhuis Groeninge
Kortrijk, West Vlaanderen, 8500
UZ Leuven
Leuven, Vlaams Brabant, 3000
Centre Hospitalier Regional de la Citadelle
Liège, 4000
AZ Oostende
Ostend, West Vlaanderen, 8400
Poland5 sites
Medical University of Lodz
Lodz, 90-549
Clinmedica Research sp zo.o.
Skierniewice, Łódź Voivodeship, 96-100
Wojewodzki Szpital Zespolony - Ludwik Rydygier Provincial Hospital
Torun, Kuyavian-Pomeranian Voivodeship, 87-100
UCK Medical University of Warsaw
Warsaw, Masovian Voivodeship, 02-097
NZOZ Gemini
Żychlin, 62-571
United States4 sites
Flourish Research - Miami (Kendall) (Formerly Clinical Site Partners)
Miami, Florida, 33186
Arensia Exploratory Medicine Clinic
Phoenix, Arizona, 85015
Harbor UCLA Medical Center
Torrance, California, 90509
Flourish Research - Orlando (Formerly Clinical Site Partners)
Winter Park, Florida, 32789
Czechia4 sites
Medicus Services s.r.o.
Brandýs nad Labem-Stará Boleslav, 25001
University Hospital Brno
Brno, South Moravian, 62500
Edumed
Jaroměř, 55101
Fakultni Nemocnice v Motole
Prague, Central Bohemian, 15006
Greece4 sites
First Cardiology Clinic University of Athens
Athens, Attica, 11527
Athens Naval Hospital
Athens, Attikh, 11521
General University Hospital Attikon
Chaïdári, 12462
Larissa University Hospital
Larissa, 41110
South Africa4 sites
Worthwhile Clinical Trials
Benoni, Gauteng, 1500
Dr M I Sarvan,R Moodley & partners
Durban, KwaZulu-Natal, 4321
Into Research
Groenkloof, Gauteng, 0181
Kuils River Hospital
Kuils River, Western Cape, 7580
South Korea4 sites
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620
Severance Hospital at Yonsei University College of Medicine
Seoul, Seodaemun-gu, 03722
Korea University Guro Hospital
Seoul, 8308
Wonju Severance Christian Hospital
Wŏnju, Gangwon-do, 26426
Spain4 sites
Hospital Universitario Virgen de la Arrixaca
El Palmar, Murcia, 30120
Hospital Universitario Virgen Macarena Unidad Coronaria 1 planta
Seville, 41009
Hospital Arnau de Vilanova
Valencia, 46015
Virgen de las Montañas Hospital
Villamartín, Cadiz, 11650
Bulgaria3 sites
MHAT Haskovo
Haskovo, 6300
University Multiprofile Hospital for Active Treatment Plovdiv
Plovdiv, 4000
Arensia Exploratory Medicine Clinic at MBAL Sveta Sofia
Sofia, 1618
Romania2 sites
Arensia Exploratory Medicine Clinic at Monza Bucharest
Bucharest, 11658
Sc Arensia Exploratory Medicine Srl
Cluj-Napoca, 400006
Georgia1 site
Arensia Exploratory Medicine at the Research Institute of Clinical Medicine
Tbilisi, 0112
Moldova1 site
Pmsi Republican Clinical Hospital Timofei Mosneaga
Chisinau, MD-2025
About this study
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of a Single Dose of REGN5381, an NPR1 Monoclonal Antibody Agonist, in Patients With Chronic Heart Failure With Reduced Ejection Fraction
This study is researching an experimental drug called REGN5381 (called "study drug"). The study is focused on patients with heart failure with reduced ejection fraction (ie, the heart is not functioning as well as it should).
The aim of the study is to see how safe, tolerable, and effective the study drug is.
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 study drug less effective or could lead to side effects)
Read the detailed description
Enrollment for the Part A2 low eGFR cohort has been closed
- Conditions
- Heart Failure
- Being tested
- REGN5381, Placebo
- Keywords
- Heart failure with reduced ejection fraction (HFrEF), Reduced ejection fraction, N-terminal pro-brain natriuretic peptide (NT-proBNP) hormone
- 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 intravenous (IV) infusion
PlaceboDrug
Single dose IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Part A1 High Dose | Experimental | Single ascending dose cohort Receives: Drug: REGN5381 |
| Part A1 Low Dose | Experimental | Single ascending dose cohort Receives: Drug: REGN5381 |
| Part A1 Optional | Experimental | Single ascending dose cohort Receives: Drug: REGN5381 |
| Part A2 High Dose, sacubitril-valsartan group | Experimental | Single ascending dose cohort Receives: Drug: REGN5381 |
| Part A2 Low Dose, sacubitril-valsartan group | Experimental | Single ascending dose cohort Receives: Drug: REGN5381 |
| Placebo for Part A2, sacubitril-valsartan group | Placebo comparator | Not described Receives: Drug: Placebo |
| Part A2 High Dose, Low estimated glomerular filtration rate (eGFR) group | Experimental | Single ascending dose cohort. Note: This group has been closed Receives: Drug: REGN5381 |
| Part A2 Low Dose, Low eGFR group | Experimental | Single ascending dose cohort. Note: This group has been closed Receives: Drug: REGN5381 |
| Placebo for Part A2, Low eGFR group | Placebo comparator | Note: This group has been closed Receives: Drug: Placebo |
| Part B High Dose | Experimental | Not described Receives: Drug: REGN5381 |
| Part B Low Dose | Experimental | Not described Receives: Drug: REGN5381 |
| Part A1 and Part B Placebo Only | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in circulating N-Terminal pro-Brain Natriuretic Peptide (NTproBNP)
Measured: Day 8
Secondary outcomes (13)
Occurrence of Treatment Emergent Adverse Events (TEAEs)
Measured: Through week 16
Severity of TEAEs
Measured: Through week 16
Change from baseline in circulating NT-proBNP
Measured: Week 2
Change from baseline in circulating NT-proBNP
Measured: Week 3
Change from baseline in circulating NT-proBNP
Measured: Week 4
Change from baseline in circulating NT-proBNP
Measured: Up to week 16
Change from baseline in Systolic Blood Pressure (SBP)
Measured: Each visit through week 16
Change from baseline in Diastolic Blood Pressure (DBP)
Measured: Each visit through week 16
Change from baseline in Mean Arterial Pressure (MAP)
Measured: Each visit through week 16
Change from baseline in Heart Rate (HR)
Measured: Each visit through week 16
Concentrations of REGN5381 in serum
Measured: Through week 16
Incidence of Anti-Drug Antibodies (ADAs) to REGN5381
Measured: Through week 16
Magnitude of ADAs to REGN5381
Measured: Through week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2024
- Study start11 Apr 2024
- Primary completion17 Sep 2025
- Study completion29 Dec 2025
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 89 participants (actual)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials Administrator, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06237309
- Sponsor's protocol ID
- R5381-HF-22118
- Other IDs
- 2023-508568-31-00, 2023
- Acronym
- NATRIX-BNP
- Status last verified
- Jan 2026
- First submitted
- 23 Jan 2024
- Last updated
- 14 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of a Single Dose of REGN5381, an NPR1 Monoclonal Antibody Agonist, in Patients With Chronic Heart Failure With Reduced Ejection Fraction
- ClinicalTrials.gov ID
- NCT06237309
- Acronym / sponsor ID
- NATRIX-BNP / R5381-HF-22118
- Conditions
- Heart Failure
- Keywords
- Heart failure with reduced ejection fraction (HFrEF), Reduced ejection fraction, N-terminal pro-brain natriuretic peptide (NT-proBNP) hormone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision
- Enrolment
- 89 participants (actual)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 11 Apr 2024 (actual)
- Primary completion
- 17 Sep 2025 (actual)
- Study completion
- 29 Dec 2025 (actual)
- First posted
- 1 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is researching an experimental drug called REGN5381 (called "study drug"). The study is focused on patients with heart failure with reduced ejection fraction (ie, the heart is not functioning as well as it should).
The aim of the study is to see how safe, tolerable, and effective the study drug is.
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 study drug less effective or could lead to side effects)
Detailed description
Enrollment for the Part A2 low eGFR cohort has been closed
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Part A1 High Dose | Experimental | Drug: REGN5381Single ascending dose cohort |
| Part A1 Low Dose | Experimental | Drug: REGN5381Single ascending dose cohort |
| Part A1 Optional | Experimental | Drug: REGN5381Single ascending dose cohort |
| Part A2 High Dose, sacubitril-valsartan group | Experimental | Drug: REGN5381Single ascending dose cohort |
| Part A2 Low Dose, sacubitril-valsartan group | Experimental | Drug: REGN5381Single ascending dose cohort |
| Placebo for Part A2, sacubitril-valsartan group | Placebo comparator | Drug: Placebo |
| Part A2 High Dose, Low estimated glomerular filtration rate (eGFR) group | Experimental | Drug: REGN5381Single ascending dose cohort. Note: This group has been closed |
| Part A2 Low Dose, Low eGFR group | Experimental | Drug: REGN5381Single ascending dose cohort. Note: This group has been closed |
| Placebo for Part A2, Low eGFR group | Placebo comparator | Drug: PlaceboNote: This group has been closed |
| Part B High Dose | Experimental | Drug: REGN5381 |
| Part B Low Dose | Experimental | Drug: REGN5381 |
| Part A1 and Part B Placebo Only | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Body mass index (BMI) between 18 and 45 kg/m^2, inclusive, at initial screening visit
- Diagnosis of chronic heart failure
- Left ventricular ejection fraction 20-49% by echocardiogram performed within 3 months of screening
- Plasma NT-proBNP ≥800 pg/mL (or ≥1000 pg/mL if in atrial fibrillation) at screening (visit 1) and NT-proBNP ≥600 pg/mL (or ≥800 pg/mL if in atrial fibrillation) approximately 30 days prior to randomization (visit 5)
- Receiving optimized standard of care therapy for heart failure as described in the protocol
Key exclusion criteria (11 listed)
- Hospital discharge within 180 days of anticipated randomization
- Resting SBP that remains out of range after two repeated measurements prior to randomization as described in the protocol
- Current or recent diagnosis of acute coronary syndrome or myocardial infarction as described in the protocol
- History of symptomatic autonomic dysfunction as evidenced by orthostatic hypotension and/or syncope
- Unexplained syncope <12 months prior to initial screening or during the Run-in period
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| REGN5381Single dose intravenous (IV) infusion | Drug | Part A1 High Dose, Part A1 Low Dose, Part A1 Optional, Part A2 High Dose, Low estimated glomerular filtration rate (eGFR) group, Part A2 High Dose, sacubitril-valsartan group, Part A2 Low Dose, Low eGFR group, Part A2 Low Dose, sacubitril-valsartan group, Part B High Dose, Part B Low Dose |
| PlaceboSingle dose IV infusion | Drug | Part A1 and Part B Placebo Only, Placebo for Part A2, Low eGFR group, Placebo for Part A2, sacubitril-valsartan group |
Primary outcome
Change from baseline in circulating N-Terminal pro-Brain Natriuretic Peptide (NTproBNP)
Time frame: Day 8
13 secondary outcomes
Occurrence of Treatment Emergent Adverse Events (TEAEs)
Time frame: Through week 16
Severity of TEAEs
Time frame: Through week 16
Change from baseline in circulating NT-proBNP
Time frame: Week 2
Change from baseline in circulating NT-proBNP
Time frame: Week 3
Change from baseline in circulating NT-proBNP
Time frame: Week 4
Change from baseline in circulating NT-proBNP
Time frame: Up to week 16
Change from baseline in Systolic Blood Pressure (SBP)
Time frame: Each visit through week 16
Change from baseline in Diastolic Blood Pressure (DBP)
Time frame: Each visit through week 16
Change from baseline in Mean Arterial Pressure (MAP)
Time frame: Each visit through week 16
Change from baseline in Heart Rate (HR)
Time frame: Each visit through week 16
Concentrations of REGN5381 in serum
Time frame: Through week 16
Incidence of Anti-Drug Antibodies (ADAs) to REGN5381
Time frame: Through week 16
Magnitude of ADAs to REGN5381
Time frame: Through week 16
Results and safety
The study was stopped early (reason given: Sponsor decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2026.
- Individual participant dataSharing planned: Yes. All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials Administrator study director
Regeneron Pharmaceuticals
44 sites in 12 countries: see every site and its status.
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 44 sites in 12 countries.
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 11 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: stopped early, as of the sponsor's last update on 14 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 44 sites in Belgium, Poland, United States, Czechia, Greece and 7 more countries. 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. Some participants in this study may receive a placebo. 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?
The study was stopped early (reason given: Sponsor decision). Results are not available in the source record.
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?
Change from baseline in circulating N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) (time frame: Day 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Jan 2026.