REGN5381 in Adult Participants With Heart Failure With Reduced Ejection Fraction (NATRIX-BNP)

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 2

Conditions: Heart Failure

Treatments: Drug: REGN5381; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06237309

R5381-HF-22118

2023-508568-31-00 (Registry Identifier)

Details and patient eligibility

About

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)

Enrollment: 391 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria

1. Body mass index (BMI) between 18 and 45 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 ≥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 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)
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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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391 participants in 12 patient groups, including a placebo group

Part A1 High Dose

Experimental group

Description:

Single ascending dose cohort

Treatment:

Drug: REGN5381

Part A1 Low Dose

Experimental group

Description:

Single ascending dose cohort

Treatment:

Drug: REGN5381

Part A1 Optional

Experimental group

Description:

Single ascending dose cohort

Treatment:

Drug: REGN5381

Part A2 High Dose, sacubitril-valsartan group

Experimental group

Description:

Single ascending dose cohort

Treatment:

Drug: REGN5381

Part A2 Low Dose, sacubitril-valsartan group

Experimental group

Description:

Single ascending dose cohort

Treatment:

Drug: REGN5381

Placebo for Part A2, sacubitril-valsartan group

Placebo Comparator group

Treatment:

Drug: Placebo

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

Experimental group

Description:

Single ascending dose cohort

Treatment:

Drug: REGN5381

Part A2 Low Dose, Low eGFR group

Experimental group

Description:

Single ascending dose cohort

Treatment:

Drug: REGN5381

Placebo for Part A2, Low eGFR group

Placebo Comparator group

Treatment:

Drug: Placebo

Part B High Dose

Experimental group

Treatment:

Drug: REGN5381

Part B Low Dose

Experimental group

Treatment:

Drug: REGN5381

Part A1 and Part B Placebo Only

Placebo Comparator group

Treatment:

Drug: Placebo