Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LCZ696 Followed by a 52-week Study of LCZ696 Compared With Enalapril in Pediatric Patients With Heart Failure

• Status: Active, not recruiting
• Trial end date: 2021-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This study consist of two parts (Part 1 and Part 2). The purpose of Part 1 is to evaluate the way the body absorbs, distributes and removes the drug LCZ696. This will help determine the proper dose of LCZ696 for Part 2 of the study.

The purpose for Part 2 is to compare the effectiveness and safety of LCZ696 with enalapril in pediatric heart failure patients over 52 weeks of treatment.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Treatments: Enalapril; Enalaprilat; LCZ 696; Sacubitril and valsartan sodium hydrate drug combination

Criteria

Key Inclusion Criteria:

• Chronic heart failure resulting from left ventricular systolic dysfunction, and receiving chronic HF therapy (if not newly diagnosed)

• NYHA classification II-IV (older children: 6 to <18 years old) or Ross CHF classification II-IV (younger children: < 6 years old)

• Systemic left ventricular ejection fraction ≤ 40% or fractional shortening ≤20%

• For Part 1 study: Patients must be treated with an ACEI or ARB prior to screening. Patients in Group 1 and 2 must be currently treated with the dose equivalent of at least enalapril 0.2 mg/kg prior to the LCZ696 3.1 mg/kg administration. Group 3 patients will participate in LCZ696 0.8 mg/kg and not LCZ696 3.1 mg/kg.

• Biventricular physiology with systemic left ventricle

Key Exclusion Criteria:

• Patient with single ventricle or systemic right ventricle

• Patients listed for heart transplantation (as United Network for Organ Sharing status 1A) or hospitalized waiting for transplant (while on inotropes or with ventricular assist device)

• Sustained or symptomatic dysrhythmias uncontrolled with drug or device therapy

• Patients that have had cardiovascular surgery or percutaneous intervention to palliate or correct congenital cardiovascular malformations within 3 months of the screening visit. Patients anticipated to undergo corrective heart surgery during the 12 months after entry into Part 2

• Patients with unoperated obstructive or severe regurgitant valvular (aortic, pulmonary, or tricuspid) disease, or significant systemic ventricular outflow obstruction or aortic arch obstruction

• Patients with restrictive or hypertrophic cardiomyopathy

• Active myocarditis

• Renal vascular hypertension (including renal artery stenosis)

• Moderate-to severe obstructive pulmonary disease

• Serum potassium > 5.3 mmol/L

• History of angioedema

• Allergy or hypersensitivity to ACEI / ARB