Heart Failure
Conditions
Keywords
Heart failure with reduced ejection fraction (HFrEF), Reduced ejection fraction, N-terminal pro-brain natriuretic peptide (NT-proBNP) hormone
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
Interventions
DRUGREGN5381
Single dose intravenous (IV) infusion
DRUGPlacebo
Single dose IV infusion
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key 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 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. 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 Note: Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in circulating N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) | Day 8 |
Secondary
| Measure | Time frame |
|---|---|
| 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 Systolic Blood Pressure (SBP) | Each visit through week 16 |
| Magnitude of ADAs to REGN5381 | Through week 16 |
| Change from baseline in Mean Arterial Pressure (MAP) | Each visit through week 16 |
| Change from baseline in Heart Rate (HR) | Each visit through week 16 |
| Concentrations of REGN5381 in serum | Through week 16 |
| Incidence of Anti-Drug Antibodies (ADAs) to REGN5381 | Through week 16 |
| Change from baseline in Diastolic Blood Pressure (DBP) | Each visit through week 16 |
Countries
Belgium, Bulgaria, Czechia, Georgia, Greece, Moldova, Poland, Romania, South Africa, South Korea, Spain, United States
Outcome results
None listed