REGN5381 in Adult Participants With Heart Failure With Reduced Ejection Fraction

NCT06237309 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: R5381-HF-221182023-508568-31-00
• Study Type: interventional
• Target: 89
• Locations: 12 countries
• Sites: 44

Brief 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. 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)

Conditions

Heart Failure

Keywords

Heart failure with reduced ejection fraction (HFrEF); Reduced ejection fraction; N-terminal pro-brain natriuretic peptide (NT-proBNP) hormone

Outcome Measures

Primary Outcomes (1)

• Change from baseline in circulating N-Terminal pro-Brain Natriuretic Peptide (NTproBNP)

  Day 8

Secondary Outcomes (13)

• Occurrence of Treatment Emergent Adverse Events (TEAEs)

  Through week 16

• Severity of TEAEs

  Through week 16

• Change from baseline in circulating NT-proBNP

  Week 2

• Change from baseline in circulating NT-proBNP

  Week 3

• Change from baseline in circulating NT-proBNP

  Week 4

Study Arms (12)

Part A1 High Dose

EXPERIMENTAL

Single ascending dose cohort

Drug: REGN5381

Part A1 Low Dose

EXPERIMENTAL

Single ascending dose cohort

Drug: REGN5381

Part A1 Optional

EXPERIMENTAL

Single ascending dose cohort

Drug: REGN5381

Part A2 High Dose, sacubitril-valsartan group

EXPERIMENTAL

Single ascending dose cohort

Drug: REGN5381

Part A2 Low Dose, sacubitril-valsartan group

EXPERIMENTAL

Single ascending dose cohort

Drug: REGN5381

Placebo for Part A2, sacubitril-valsartan group

PLACEBO COMPARATOR

Drug: Placebo

Part A2 High Dose, Low estimated glomerular filtration rate (eGFR) group

EXPERIMENTAL

Single ascending dose cohort. Note: This group has been closed

Drug: REGN5381

Part A2 Low Dose, Low eGFR group

EXPERIMENTAL

Single ascending dose cohort. Note: This group has been closed

Drug: REGN5381

Placebo for Part A2, Low eGFR group

PLACEBO COMPARATOR

Note: This group has been closed

Drug: Placebo

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

Interventions

REGN5381 DRUG

Single dose intravenous (IV) infusion

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

Placebo DRUG

Single dose IV infusion

Part A1 and Part B Placebo Only; Placebo for Part A2, Low eGFR group; Placebo for Part A2, sacubitril-valsartan group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• a. 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (44)

Arensia Exploratory Medicine Clinic

Phoenix, Arizona, 85015, United States

Location

Harbor UCLA Medical Center

Torrance, California, 90509, United States

Location

Flourish Research - Miami (Kendall) (Formerly Clinical Site Partners)

Miami, Florida, 33186, United States

Location

Flourish Research - Orlando (Formerly Clinical Site Partners)

Winter Park, Florida, 32789, United States

Location

Grand Hopital de Charleroi

Gilly, Hainaut, 6060, Belgium

Location

Anima Research Center

Alken, Limburg, 3570, Belgium

Location

Onze Lieve Vrouw Ziekenhuis Aalst

Aalst, Oost-Vlaanderen, 9300, Belgium

Location

UZ Leuven

Leuven, Vlaams Brabant, 3000, Belgium

Location

Algemeen Ziekenhuis St Jan Brugge Oostende Av

Bruges, West Flanders, 8000, Belgium

Location

Algemeen Ziekenhuis Groeninge

Kortrijk, West Vlaanderen, 8500, Belgium

Location

AZ Oostende

Ostend, West Vlaanderen, 8400, Belgium

Location

Centre Hospitalier Regional de la Citadelle

Liège, 4000, Belgium

Location

MHAT Haskovo

Haskovo, 6300, Bulgaria

Location

University Multiprofile Hospital for Active Treatment Plovdiv

Plovdiv, 4000, Bulgaria

Location

Arensia Exploratory Medicine Clinic at MBAL Sveta Sofia

Sofia, 1618, Bulgaria

Location

Fakultni Nemocnice v Motole

Prague, Central Bohemian, 15006, Czechia

Location

University Hospital Brno

Brno, South Moravian, 62500, Czechia

Location

Medicus Services s.r.o.

Brandýs nad Labem-Stará Boleslav, 25001, Czechia

Location

Edumed

Jaroměř, 55101, Czechia

Location

Arensia Exploratory Medicine at the Research Institute of Clinical Medicine

Tbilisi, 0112, Georgia

Location

First Cardiology Clinic University of Athens

Athens, Attica, 11527, Greece

Location

Athens Naval Hospital

Athens, Attikh, 11521, Greece

Location

General University Hospital Attikon

Chaïdári, 12462, Greece

Location

Larissa University Hospital

Larissa, 41110, Greece

Location

Pmsi Republican Clinical Hospital Timofei Mosneaga

Chisinau, MD-2025, Moldova

Location

Wojewodzki Szpital Zespolony - Ludwik Rydygier Provincial Hospital

Torun, Kuyavian-Pomeranian Voivodeship, 87-100, Poland

Location

UCK Medical University of Warsaw

Warsaw, Masovian Voivodeship, 02-097, Poland

Location

Medical University of Lodz

Lodz, 90-549, Poland

Location

NZOZ Gemini

Żychlin, 62-571, Poland

Location

Clinmedica Research sp zo.o.

Skierniewice, Łódź Voivodeship, 96-100, Poland

Location

Arensia Exploratory Medicine Clinic at Monza Bucharest

Bucharest, 11658, Romania

Location

Sc Arensia Exploratory Medicine Srl

Cluj-Napoca, 400006, Romania

Location

Worthwhile Clinical Trials

Benoni, Gauteng, 1500, South Africa

Location

Into Research

Groenkloof, Gauteng, 0181, South Africa

Location

Dr M I Sarvan,R Moodley & partners

Durban, KwaZulu-Natal, 4321, South Africa

Location

Kuils River Hospital

Kuils River, Western Cape, 7580, South Africa

Location

Wonju Severance Christian Hospital

Wŏnju, Gangwon-do, 26426, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Severance Hospital at Yonsei University College of Medicine

Seoul, Seodaemun-gu, 03722, South Korea

Location

Korea University Guro Hospital

Seoul, 8308, South Korea

Location

Virgen de las Montañas Hospital

Villamartín, Cadiz, 11650, Spain

Location

Hospital Universitario Virgen de la Arrixaca

El Palmar, Murcia, 30120, Spain

Location

Hospital Universitario Virgen Macarena Unidad Coronaria 1 planta

Seville, 41009, Spain

Location

Hospital Arnau de Vilanova

Valencia, 46015, Spain

Location

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Clinical Trials Administrator

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2024
• First Posted: February 1, 2024
• Study Start: April 11, 2024
• Primary Completion: September 17, 2025
• Study Completion: December 29, 2025
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: When Regeneron has: * received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development * made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry) * the legal authority to share the data, and * ensured the ability to protect participant privacy
• Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf

Locations

RO (2); GR (4); US (4); CZ (4); KR (4); ES (4); BU (3); GE (1); PL (5); MO (1); BE (8); ZA (4)