Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LCZ696 Followed by a 52-week Study of LCZ697 Compared With Enalapril in Pediatric Patients With Heart Failure

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

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

JPRN

Registry ID

JPRN-jRCT2080223850

Enrollment

360

Registered

2018-03-30

Start date

2018-09-25

Completion date

Unknown

Last updated

2026-06-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pediatric Heart Failure

Interventions

investigational material(s) Generic name etc : LCZ696 INN of investigational material : sacubitril/valsartan Therapeutic category code : 214 Antihypertensives Dosage and Administration for Investigati

Eligibility

Sex/Gender

All

Inclusion criteria

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

Exclusion criteria

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 Other protocol-defined inclusion/exclusion criteria may apply.

Design outcomes

Primary

Measure	Time frame
pharmacokinetics 1.Part 1: Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Maximum drug concentration in plasma (Cmax) [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, and optional 24 hours post dosing ] Cmax will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods. pharmacokinetics 2.Part 1: Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Time to maximum plasma concentration (Tmax) [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, and optional 24 hours post dosing ] Tmax will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods. pharmacokinetics 3.Part 1: Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): area under the plasma concentration-time curve from time zero to infinity (AUCinf) and area under the plasma concentration-time curve from time zero to last (AUClast) [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, and optional 24 hours post dosing ] AUCinf and AUClast will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods. pharmacokinetics 4.Part 1: Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Clearance from plasma (CL/F) [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, and optional 24 hours post dosing ] CL/F will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods. pharmacokinetics 5.Part 1: Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Time required to drug concentration to decrease by half (T 1/2) [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, and optional 24 hours post dosing ] T 1/2 will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods pharmacodynamics 6.Part 1: Pharmacodynamics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Plasma N-terminal pro-b	—

Measure

Time frame

pharmacokinetics 1.Part 1: Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Maximum drug concentration in plasma (Cmax) [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, and optional 24 hours post dosing ] Cmax will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods. pharmacokinetics 2.Part 1: Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Time to maximum plasma concentration (Tmax) [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, and optional 24 hours post dosing ] Tmax will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods. pharmacokinetics 3.Part 1: Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): area under the plasma concentration-time curve from time zero to infinity (AUCinf) and area under the plasma concentration-time curve from time zero to last (AUClast) [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, and optional 24 hours post dosing ] AUCinf and AUClast will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods. pharmacokinetics 4.Part 1: Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Clearance from plasma (CL/F) [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, and optional 24 hours post dosing ] CL/F will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods. pharmacokinetics 5.Part 1: Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Time required to drug concentration to decrease by half (T 1/2) [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, and optional 24 hours post dosing ] T 1/2 will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods pharmacodynamics 6.Part 1: Pharmacodynamics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Plasma N-terminal pro-b

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Secondary

Measure	Time frame
efficacy 1.Part 2: Time to first occurrence of Category 1 or Category 2 event [ Time Frame: 52 weeks ] Category 1: Death; United Network for Organ Sharing (UNOS) status 1A listing for heart transplant or equivalent; Ventricular assist device (VAD)/Extracorporeal membrane oxygenation (ECMO)/mechanical ventilation requirement for life support at end of study. Category 2: Worsening HF (WHF); defined by signs and symptoms of WHF that requires an intensification of HF therapy efficacy 2.Part 2: Change from baseline in NYHA/Ross functional class [ Time Frame: Baseline to 52 weeks ] NYHA/Ross functional class will be compared through 52 weeks of double-blind treatment efficacy 3.Part 2: Change from baseline in Patient Global impression of severity score (PGIS) scale [ Time Frame: Baseline to 52 weeks ] PGIS scale will be compared for LCZ696 and enalapril through 52 weeks of double-blind treatment pharmacokinetics 4.Part 2: Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Clearance from plasma in steady state (CL,ss) [ Time Frame: Week 2, 12, 52 ] The steady state population PK parameter clearance will be estimated to be used in model. pharmacokinetics 5.Part 2: Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Volume of distribution in steady state [ Time Frame: Week 2, 12, 52 ] The steady state population PK parameter volume of distribution will be estimated to be used in model. pharmacokinetics 6.Part 2: Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Absorption rate constant in steady state (Ka,ss) [ Time Frame: Week 2, 12, 52 ] The steady state population PK parameter Ka will be estimated to be used in model. pharmacokinetics 7.Part 2: Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Time required to drug concentration to decrease by half in steady state (T 1/2,ss) [ Time Frame: Week 2, 12, 52 ] The steady state population PK parameter T 1/2 will be estimated to be used in	—

Measure

Time frame

efficacy 1.Part 2: Time to first occurrence of Category 1 or Category 2 event [ Time Frame: 52 weeks ] Category 1: Death; United Network for Organ Sharing (UNOS) status 1A listing for heart transplant or equivalent; Ventricular assist device (VAD)/Extracorporeal membrane oxygenation (ECMO)/mechanical ventilation requirement for life support at end of study. Category 2: Worsening HF (WHF); defined by signs and symptoms of WHF that requires an intensification of HF therapy efficacy 2.Part 2: Change from baseline in NYHA/Ross functional class [ Time Frame: Baseline to 52 weeks ] NYHA/Ross functional class will be compared through 52 weeks of double-blind treatment efficacy 3.Part 2: Change from baseline in Patient Global impression of severity score (PGIS) scale [ Time Frame: Baseline to 52 weeks ] PGIS scale will be compared for LCZ696 and enalapril through 52 weeks of double-blind treatment pharmacokinetics 4.Part 2: Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Clearance from plasma in steady state (CL,ss) [ Time Frame: Week 2, 12, 52 ] The steady state population PK parameter clearance will be estimated to be used in model. pharmacokinetics 5.Part 2: Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Volume of distribution in steady state [ Time Frame: Week 2, 12, 52 ] The steady state population PK parameter volume of distribution will be estimated to be used in model. pharmacokinetics 6.Part 2: Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Absorption rate constant in steady state (Ka,ss) [ Time Frame: Week 2, 12, 52 ] The steady state population PK parameter Ka will be estimated to be used in model. pharmacokinetics 7.Part 2: Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Time required to drug concentration to decrease by half in steady state (T 1/2,ss) [ Time Frame: Week 2, 12, 52 ] The steady state population PK parameter T 1/2 will be estimated to be used in

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Countries

Africa, Asia except Japan, Europe, Japan, North America, Oceania, South America

Outcome results

None listed

Source: JPRN (via WHO ICTRP) · Data processed: Jul 3, 2026