Heart Failure MedDRA version: 20.0 Level: LLT Classification code 10010684 Term: Congestive heart failure System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Product Name: REGN5381
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: REGN5381
Other descriptive name: REGN5381
Concentration unit: mg/ml milligram(s)/millilitre
Conc
Sponsors
Regeneron Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Body mass index (BMI) between 18 and 35 kg/m^2, inclusive, rounded to the nearest whole number 2. Ambulatory participants with New York Heart Association (NYHA) class II/III heart failure and at least 1 sign and/or symptom of congestion (eg, dyspnea on exertion, worsening edema, orthopnea, etc.) 3. Left ventricular ejection fraction (LVEF) =20 % and 1000 pg/mL or Brain Natriuretic Peptide (active form) (BNP) >300 pg/mL as described in the protocol within 30 days prior to randomization measured by the local laboratory (only for HFrEF participants [Group A and Group B]). 7. Pulmonary capillary wedge pressure (PCWP) =15 mmHg and right artrial pressure (RAP) >5 mmHg on right heart catheterization (RHC) the morning of anticipated study drug dose administration (not applicable for HFrEF participants not taking sacubitril/valsartan [Group A] as described in the protocol). 8. Systolic blood pressure (SBP) =110 mmHg at the screening visit and on day -1 9. Hematocrit >30% at the screening visit and day -1 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 89 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 33
Exclusion criteria
Exclusion criteria: Key Exclusion Criteria: 1. Currently taking IV vasodilators and/or inotropes 2. Taking sacubitril/valsartan (only for HFrEF and HFpEF participants not taking sacubitril/valsartan [Group A and Group C, respectively]) 3. Taking a phosphodiesterase (PDE) inhibitor (eg, sildenafil), or a soluble guanylate cyclase stimulator (SGCS; ie, vericiguat) within 2 weeks of the screening visit or planning on taking valsartan/sacubitril, a PDE inhibitor, or a SGCS at any point during the study 4. More than moderate valvular regurgitation/stenosis (ie, moderate-to-severe or severe) on echocardiogram within 90 days prior to randomization 5. Known infiltrative or hypertrophic cardiomyopathy 6. Acute coronary syndrome within prior 6 months of randomization 7. History of cardiac arrest 8. Cardiac surgery within 3 months of randomization 9. Pacemaker or defibrillator placement within prior 30 days of randomization 10. Severe chronic obstructive pulmonary disease (COPD) (defined as Forced Expiratory Volume in 1st second [FEV1] <50% of predicted or Global Initiative for Chronic Obstructive Lung Disease [GOLD] 3 or 4) 11. Pulmonary arterial hypertension (World Health Organization [WHO] Group 1) and any medical history at any time of more than moderate pulmonary hypertension (ie, moderate-to-severe, or severe pulmonary hypertension, as described in the protocol 12. Congenital heart disease (repaired or unrepaired) 13. Inability to lie flat for cardiac catheterization Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of single doses of REGN5381 in patients with heart failure with evidence of congestion.;Secondary Objective: • Evaluate the effects of single doses of REGN5381 on hemodynamic parameters • Evaluate the effects of REGN5381 on a clinical biomarker of heart failure severity • Characterize the pharmacokinetics (PK) of single doses of REGN5381 • Assess the immunogenicity of REGN5381;Primary end point(s): Incidence and severity of treatment-emergent adverse events (TEAEs);Timepoint(s) of evaluation of this end point: Through the end-of-study (EOS) visit up to 126 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1-6: Over 6 hours post-dose administration 7-10: Over the first 6 hours, 24 hours post-dose administration (day 1), through the EOS visit up to 126 days 11: To 6 hours, 24 hours post-dose administration (day 1), through the EOS visit up to 126 days 12-13: Through the EOS visit, up to 126 days;Secondary end point(s): 1: Change from baseline in pulmonary capillary wedge pressure (PCWP) 2: Change from baseline right atrial pressure (RAP) 3: Change from baseline cardiac output (CO) 4: Change from baseline systemic vascular resistance (SVR) 5: Change from baseline mean pulmonary artery pressure (mPAP) 6: Change from baseline pulmonary vascular resistance (PVR) 7: Change from baseline in systolic blood pressure (SBP) 8: Change from baseline in diastolic blood pressure (DBP) 9: Change from baseline in mean arterial pressure (MAP) 10: Change from baseline in pulse rate (PR) 11: Change from baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP) 12: Concentrations of REGN5381 in serum 13: Immunogenicity, as measured by anti-drug antibodies (ADA) to REGN5381 | — |
Countries
Belgium, Hungary, Moldova, Republic of
Contacts
Public ContactClinical Trial Information
Regeneron Pharmaceuticals, Inc.
Outcome results
None listed