Clinical trial NCT06237309: REGN5381 in Adult Participants With Heart Failure With Reduced Ejection Fraction
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Heart Failure
Keywords: Heart failure with reduced ejection fraction (HFrEF)
Reduced ejection fraction
N-terminal pro-brain natriuretic peptide (NT-proBNP) hormone
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-02-01
Enrollment: 391
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility 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

Primary outcomes:
measure: Change from baseline in circulating N-terminal pro-brain natriuretic peptide (NTproBNP)
timeFrame: Day 8
Secondary outcomes:
measure: Occurrence of treatment emergent adverse events (TEAEs)
timeFrame: Through week 16
measure: Severity of TEAEs
timeFrame: Through week 16
measure: Change from baseline in circulating NT-proBNP
timeFrame: Week 2
measure: Change from baseline in circulating NT-proBNP
timeFrame: Week 3
measure: Change from baseline in circulating NT-proBNP
timeFrame: Week 4
measure: Change from baseline in circulating NT-proBNP
timeFrame: Up to week 16
measure: Change from baseline in systolic blood pressure (SBP)
timeFrame: Each visit through week 16
measure: Change from baseline in diastolic blood pressure (DBP)
timeFrame: Each visit through week 16
measure: Change from baseline in mean arterial pressure (MAP)
timeFrame: Each visit through week 16
measure: Change from baseline in heart rate (HR)
timeFrame: Each visit through week 16
measure: Concentrations of REGN5381 in serum
timeFrame: Through week 16
measure: Incidence of anti-drug antibodies (ADAs) to REGN5381
timeFrame: Through week 16
measure: Titer of ADAs to REGN5381
timeFrame: Through week 16
Other outcomes:
Locations:
city: Alken
country: Belgium
facility: Anima Research Center
state: Limburg
city: Aalst
country: Belgium
facility: Onze Lieve Vrouw Ziekenhuis Aalst
state: Oost-Vlaanderen
city: Leuven
country: Belgium
facility: UZ Leuven
state: Vlaams Brabant
city: Bruges
country: Belgium
facility: Algemeen Ziekenhuis St Jan Brugge Oostende Av
state: West Flanders
city: Oostende
country: Belgium
facility: AZ Oostende
state: West Vlaanderen
city: Liege
country: Belgium
facility: Centre Hospitalier Regional de la Citadelle
city: Sofia
country: Bulgaria
facility: Arensia Exploratory Medicine Clinic at MBAL Sveta Sofia
city: Chisinau
country: Moldova, Republic of
facility: Pmsi Republican Clinical Hospital Timofei Mosneaga
city: Torun
country: Poland
facility: Wojewodzki Szpital Zespolony - Ludwik Rydygier Provincial Hospital
state: Kuyavian-Pomeranian
city: Warszawa
country: Poland
facility: UCK Medical University of Warsaw
state: Mazowieckie
city: Lodz
country: Poland
facility: Medical University of Lodz
city: Bucharest
country: Romania
facility: Arensia Exploratory Medicine Clinic at Monza Bucharest
city: Cluj Napoca
country: Romania
facility: Sc Arensia Exploratory Medicine Srl
city: Villamartin
country: Spain
facility: Virgen de las Montañas Hospital
state: Cadiz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena Unidad Coronaria 1 planta
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trials Administrator
role: STUDY_DIRECTOR
References: