Multicenter, open-label, study to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of LCZ696 followed by a 52-week randomized, double-blind, parallel group, active-controlled study to evaluate the efficacy and safety of LCZ696 compared with Enalapril in pediatric patients from 1 month to < 18 years of age with heart failure due to systemic left ventricle systolic dysfunction.
Study ID: STU 022016-077
The purpose of this study is to determine whether pediatric heart failure (HF) patients (1 month to [Less Than] 18 years old) will derive greater clinical treatment benefit with LCZ696 compared to enalapril over 52 week treatment duration. This study includes two parts. Part 1 will confirm the dose for Part 2. Part 2 will assess the efficacy and safety of LCZ696 compared to enalapril.
Patients eligible for inclusion in this study (Part 1 and Part 2) must fulfill all of the following criteria: 1. Written informed consent by parent(s)/legal guardian(s) for the pediatric patient must be obtained before any study-specific assessment is performed.* A consent or assent may also be required for some patients depending upon their age and local requirement. 2. Male or female, inpatient or outpatient, 1 month (>=44 weeks post-conception for pre-term infants) to < 18 years of age. 3. Chronic heart failure resulting from left ventricular systolic dysfunction, and receiving chronic HF therapy (if not newly diagnosed). [Note: the study will target enrollment of 25% ACEI/ARB naive patients for Part 2 only]. 4. NYHA classification II-IV (older children: 6 to less than 18 year old) or Ross HF classification II-IV (younger children: less than 6 year old) any time prior to screening. [Note: the patient may NYHA or Ross class I at time of screening if there is a prior history of NYHA or Ross II-IV]. 5. Systemic left ventricular ejection fraction (EF) <= 40% or fractional shortening <=20% (assessed by echocardiogram, MRI, MUGA or left ventricular angiogram within 1 month before patient begins Part 1 or Part 2). 6. Biventricular physiology with systemic left ventricle. 7. For Part 1 PK/PD, patients must be treated with an ACEI or ARB prior to screening. For Part 1 PK/PD, patients in Group 1 and 2 must be currently treated with the dose equivalent of at least enalapril 0.2 mg/kg (Table 3-1) prior to the LCZ696 3.1 mg/kg single dose assessment. (Group 3 patients only participate in the LCZ696 0.8 mg/kg and not the second LCZ696 3.1 mg/kg PK/PD assessment) 8. HF etiologies include: Congenital Cardiac Malformation with systemic ventricular systolic dysfunction; Idiopathic Cardiomyopathy; Familial/Inherited and/or Genetic Cardiomyopathy; History of Myocarditis; Neuromuscular Disorder; Inborn Error of Metabolism; Mitochondrial Disorder; Acquired (Chemotherapy, Iatrogenic, Infection, Rheumatic, Nutritional); Ischemic (e.g. Kawasaki Disease, post-operative); Left ventricular noncompaction.