A Trial to Learn How REGN5381 Works and How Safe it is in Adults With Heart Failure With Reduced Ejection Fraction (HFrEF)

Heart Failure Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06237309
• Other study ID #: R5381-HF-22118
• Secondary ID: 2023-508568-31-0
• Status: Recruiting
• Phase: Phase 2
• Start date: April 11, 2024
• Est. completion date: April 15, 2026

Study information

• Verified date: May 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 391
• Est. completion date: April 15, 2026
• Est. primary completion date: January 2, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria

1. Body mass index (BMI) between 18 and 40 kg/m2, 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 =900 pg/mL (or =1200 pg/mL if in atrial fibrillation) at screening and within approximately 30 days of randomization

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

6. Sacubitril-valsartan cohort only: treatment with sacubitril-valsartan at screening and at baseline

7. Low eGFR cohort only: eGFR of 30-45 mL/min/1.73 m2 at screening and within approximately 30 days of randomization Key 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. Estimated glomerular filtration rate (eGFR) of <45 mL/min/1.73 m2 according to locally used formula (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] preferred), at screening (eGFR of 30-45 mL/min/1.73 m2 required for participants in the low eGFR cohort, and if supported by safety data, Part B will include eGFR =30 mL/min/1.73 m2)

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

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

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

7. 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

8. Uncorrected congenital heart disease

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

10. 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

11. Current chronic lung disease requiring long-term oxygen therapy Note: Other protocol-defined inclusion/ exclusion criteria apply

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• REGN5381
Single dose intravenous (IV) infusion
• Placebo
Single dose IV infusion

Locations

Country	Name	City	State
Moldova, Republic of	Republican Clinical Hospital	Chisinau

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Country where clinical trial is conducted

Moldova, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in circulating N-terminal pro-brain natriuretic peptide (NTproBNP)		Day 8
Secondary	Occurrence of treatment emergent adverse events (TEAEs)		Through week 16
Secondary	Severity of TEAEs		Through week 16
Secondary	Change from baseline in circulating NT-proBNP		Week 2
Secondary	Change from baseline in circulating NT-proBNP		Week 3
Secondary	Change from baseline in circulating NT-proBNP		Week 4
Secondary	Change from baseline in circulating NT-proBNP		Up to week 16
Secondary	Change from baseline in systolic blood pressure (SBP)		Each visit through week 16
Secondary	Change from baseline in diastolic blood pressure (DBP)		Each visit through week 16
Secondary	Change from baseline in mean arterial pressure (MAP)		Each visit through week 16
Secondary	Change from baseline in heart rate (HR)		Each visit through week 16
Secondary	Concentrations of REGN5381 in serum		Through week 16
Secondary	Incidence of anti-drug antibodies (ADAs) to REGN5381		Through week 16
Secondary	Titer of ADAs to REGN5381		Through week 16