study of jk07 in patients with chronic heart failure

Conditions: Heart Failure With Reduced Ejection Fraction; Heart Failure With Preserved Ejection Fraction

Summary: this is a phase 2, randomized, double-blind, placebo-controlled, multiple dose study to assess the safety, tolerability, and efficacy of jk07 in participants aged 18-85 with heart failure. there will be 2 cohorts in this study: cohort 1: heart failure (hf) participants with left ventricular ejection fraction (lvef) of ≤ 40%. cohort 2: heart failure (hf) participants with left ventricular ejection fraction (lvef) \> 40% and ≤ 65%.


Eligibility criteria:
inclusion criteria: * participants with new york heart association (nyha) class ii-iii. * cohort 1 - left ventricular ejection fraction (lvef) ≤ 40%. * cohort 2 - left ventricular ejection fraction (lvef) \>40% and ≤ 65%, elevated n-terminal pro b-type natriuretic peptide (nt-probnp) ≥ 600pg/ml and atrial fibrillation/flutter. * stable heart failure and on optimal medical therapy. * screening hemoglobin ≥ 9.0 g/dl. exclusion criteria: * uncontrolled hypertension. * sustained systolic blood pressure (bp) \< 90 mmhg and/or diastolic bp \< 50 mmhg on 2 consecutive (duplicate seated) readings at screening. * heart failure due to hypertrophic cardiomyopathy, restrictive and/or infiltrative cardiomyopathy, arrhythmogenic right ventricular dysplasia, fabry disease, or noonan syndrome with lv hypertrophy or a positive serum immunofixation result. * diagnosis of stress-induced (takotsubo) cardiomyopathy, myocarditis, or peripartum cardiomyopathy. * diagnosis of chemotherapy- or radiation-induced cardiomyopathy. * diagnosed with stroke or transient ischemic attack (tia) within 12 weeks of screening. * history of syncope within the last 12 weeks prior to screening or sustained ventricular tachycardia without an implantable cardioverter-defibrillator. * moderate or severe aortic and/or mitral valve stenosis. * medically documented unstable angina, acute coronary syndrome (e.g., myocardial infarction, troponin-positive with symptoms of angina or unstable angina) within the last 8 weeks prior to start of screening. * medically documented st-elevation myocardial infarction within 12 weeks of screening. * any tachycardia (inclusive of atrial fibrillation (af) or atrial flutter) with a resting ventricular rate \> 110 beats per minute at screening. * for participants with a history of af or atrial flutter, not on adequate anticoagulant therapy via non-vitamin k oral anticoagulants or warfarin if the cha2ds2-vasc score is ≥ 2 in men or ≥ 3 in women or per local guidelines. percutaneous occlusion of the left atrial appendage alone is not adequate. * af ablation within the last 12 weeks prior to screening or planned during the study duration. * symptomatic bradycardia or second (mobitz type ii)- or third-degree heart block without a pacemaker. * cardiac surgery, coronary artery revascularization or indication for coronary artery revascularization, percutaneous coronary intervention, valve repair/replacement or valvuloplasty within 12 weeks prior to screening. * implantation of a cardiac resynchronization therapy (crt) device within 12 weeks prior to screening, or intent to implant a crt device during the course of the study. * previous cardiac transplantation, or any use of mechanical circulatory support or similar device, or implantation expected after randomization. * receiving mechanical hemodynamic support or invasive mechanical ventilation within the last 8 weeks prior to screening. * receiving intravenous (iv) inotropes or iv vasopressors within the last 8 weeks prior to screening. * receiving iv vasodilators within the last 4 weeks prior to screening. * receiving noninvasive mechanical ventilation within the last 4 weeks prior to screening. the use of noninvasive ventilation for sleep disordered breathing is permitted.

Keywords: heart failure heart failure with reduced ejection fraction heart failure with preserved ejection fraction heart failure nyha class iii heart failure nyha class ii heart failure with atrial fibrillation/flutter hfref hfpef neuregulin 1 nrg-1 her3 her4 erbb3 erbb4 systolic heart failure diastolic heart failure atrial fibrillation atrial flutter