REGN5381 in Adult Participants With Heart Failure With Reduced Ejection Fraction

NCT ID: NCT06237309

Last Updated: 2026-01-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 89 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-11
• Study Completion Date: 2025-12-29

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)

Detailed Description

Enrollment for the Part A2 low eGFR cohort has been closed

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part A1 High Dose

Single ascending dose cohort

Group Type: EXPERIMENTAL

REGN5381

Intervention Type: DRUG

Single dose intravenous (IV) infusion

Part A1 Low Dose

Single ascending dose cohort

Group Type: EXPERIMENTAL

REGN5381

Intervention Type: DRUG

Single dose intravenous (IV) infusion

Part A1 Optional

Single ascending dose cohort

Group Type: EXPERIMENTAL

REGN5381

Intervention Type: DRUG

Single dose intravenous (IV) infusion

Part A2 High Dose, sacubitril-valsartan group

Single ascending dose cohort

Group Type: EXPERIMENTAL

REGN5381

Intervention Type: DRUG

Single dose intravenous (IV) infusion

Part A2 Low Dose, sacubitril-valsartan group

Single ascending dose cohort

Group Type: EXPERIMENTAL

REGN5381

Intervention Type: DRUG

Single dose intravenous (IV) infusion

Placebo for Part A2, sacubitril-valsartan group

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Single dose IV infusion

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

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

Group Type: EXPERIMENTAL

REGN5381

Intervention Type: DRUG

Single dose intravenous (IV) infusion

Part A2 Low Dose, Low eGFR group

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

Group Type: EXPERIMENTAL

REGN5381

Intervention Type: DRUG

Single dose intravenous (IV) infusion

Placebo for Part A2, Low eGFR group

Note: This group has been closed

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Single dose IV infusion

Part B High Dose

Group Type: EXPERIMENTAL

REGN5381

Intervention Type: DRUG

Single dose intravenous (IV) infusion

Part B Low Dose

Group Type: EXPERIMENTAL

REGN5381

Intervention Type: DRUG

Single dose intravenous (IV) infusion

Part A1 and Part B Placebo Only

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Single dose IV infusion

Interventions

REGN5381

Single dose intravenous (IV) infusion

Intervention Type: DRUG

Placebo

Single dose IV infusion

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Body mass index (BMI) between 18 and 45 kg/m^2, inclusive, at initial screening visit

2. Diagnosis of chronic heart failure

3. Left ventricular ejection fraction 20-49% by echocardiogram performed within 3 months of screening

4. 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)

5. Receiving optimized standard of care therapy for heart failure as described in the protocol

6. 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

7. Estimated Glomerular Filtration Rate (eGFR) levels:

1. 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

Exclusion Criteria

1. Hospital discharge within 180 days of anticipated randomization

2. Resting SBP that remains out of range after two repeated measurements prior to randomization as described in the protocol

3. Current or recent diagnosis of acute coronary syndrome or myocardial infarction as described in the protocol

4. History of symptomatic autonomic dysfunction as evidenced by orthostatic hypotension and/or syncope

5. Unexplained syncope <12 months prior to initial screening or during the Run-in period

6. 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

7. Uncorrected congenital heart disease

8. Cardiac surgery within 6 months prior to screening or any planned surgery during the study

9. 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

10. Current chronic lung disease requiring long-term oxygen therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials Administrator

Role: STUDY_DIRECTOR

Regeneron Pharmaceuticals

Locations

Arensia Exploratory Medicine Clinic

Phoenix, Arizona, United States

Harbor UCLA Medical Center

Torrance, California, United States

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

Miami, Florida, United States

Flourish Research - Orlando (Formerly Clinical Site Partners)

Winter Park, Florida, United States

Grand Hopital de Charleroi

Gilly, Hainaut, Belgium

Anima Research Center

Alken, Limburg, Belgium

Onze Lieve Vrouw Ziekenhuis Aalst

Aalst, Oost-Vlaanderen, Belgium

UZ Leuven

Leuven, Vlaams Brabant, Belgium

Algemeen Ziekenhuis St Jan Brugge Oostende Av

Bruges, West Flanders, Belgium

Algemeen Ziekenhuis Groeninge

Kortrijk, West Vlaanderen, Belgium

AZ Oostende

Ostend, West Vlaanderen, Belgium

Centre Hospitalier Regional de la Citadelle

Liège, , Belgium

MHAT Haskovo

Haskovo, , Bulgaria

University Multiprofile Hospital for Active Treatment Plovdiv

Plovdiv, , Bulgaria

Arensia Exploratory Medicine Clinic at MBAL Sveta Sofia

Sofia, , Bulgaria

Fakultni Nemocnice v Motole

Prague, Central Bohemian, Czechia

University Hospital Brno

Brno, South Moravian, Czechia

Medicus Services s.r.o.

Brandýs nad Labem-Stará Boleslav, , Czechia

Edumed

Jaroměř, , Czechia

Arensia Exploratory Medicine at the Research Institute of Clinical Medicine

Tbilisi, , Georgia

First Cardiology Clinic University of Athens

Athens, Attica, Greece

Athens Naval Hospital

Athens, Attikh, Greece

General University Hospital Attikon

Chaïdári, , Greece

Larissa University Hospital

Larissa, , Greece

Pmsi Republican Clinical Hospital Timofei Mosneaga

Chisinau, , Moldova

Wojewodzki Szpital Zespolony - Ludwik Rydygier Provincial Hospital

Torun, Kuyavian-Pomeranian Voivodeship, Poland

UCK Medical University of Warsaw

Warsaw, Masovian Voivodeship, Poland

Medical University of Lodz

Lodz, , Poland

NZOZ Gemini

Żychlin, , Poland

Clinmedica Research sp zo.o.

Skierniewice, Łódź Voivodeship, Poland

Arensia Exploratory Medicine Clinic at Monza Bucharest

Bucharest, , Romania

Sc Arensia Exploratory Medicine Srl

Cluj-Napoca, , Romania

Worthwhile Clinical Trials

Benoni, Gauteng, South Africa

Into Research

Groenkloof, Gauteng, South Africa

Dr M I Sarvan,R Moodley & partners

Durban, KwaZulu-Natal, South Africa

Kuils River Hospital

Kuils River, Western Cape, South Africa

Wonju Severance Christian Hospital

Wŏnju, Gangwon-do, South Korea

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Severance Hospital at Yonsei University College of Medicine

Seoul, Seodaemun-gu, South Korea

Korea University Guro Hospital

Seoul, , South Korea

Virgen de las Montañas Hospital

Villamartín, Cadiz, Spain

Hospital Universitario Virgen de la Arrixaca

El Palmar, Murcia, Spain

Hospital Universitario Virgen Macarena Unidad Coronaria 1 planta

Seville, , Spain

Hospital Arnau de Vilanova

Valencia, , Spain

Countries

United States; Belgium; Bulgaria; Czechia; Georgia; Greece; Moldova; Poland; Romania; South Africa; South Korea; Spain

Other Identifiers

2023-508568-31-00

Identifier Type: CTIS

Identifier Source: secondary_id

R5381-HF-22118

Identifier Type: -

Identifier Source: org_study_id