Efficacy, Safety, and Pharmacokinetics of Vericiguat in Pediatric Participants With Heart Failure Due to Left Ventricular Systolic Dysfunction (MK-1242-036)

Study Overview
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Brief Summary
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This study aims to compare the efficacy of vericiguat versus placebo on change in n-terminal pro-brain natriuretic peptide (NTproBNP) from baseline to Week 16. The primary hypothesis is Vericiguat is superior to placebo in reducing NT-proBNP at Week 16.

Official Title
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A Phase 2/3 Randomized, Placebo-Controlled, Double-blind, Clinical Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Vericiguat in Pediatric Participants With Heart Failure Due to Systemic Left Ventricular Systolic Dysfunction (VALOR)

Conditions
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Heart Failure, Left Ventricular Systolic Dysfunction

Intervention / Treatment
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* Drug: Vericiguat tablet
* Drug: Vericiguat suspension
* Drug: Placebo tablet
* Drug: Placebo suspension


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a history of symptomatic chronic heart failure (HF) resulting from systemic left ventricular (LV) systolic dysfunction Has biventricular physiology with a morphologic systemic left ventricle Is currently receiving stable medical therapy for HF Has left ventricular ejection fraction (LVEF) <45% assessed within 3 months before randomization Female is eligible to participate if not pregnant or breastfeeding, and at least one of the following: is not a participant of childbearing potential (POCBP); or is a POCBP who uses a highly effective contraceptive method; has a negative highly sensitive pregnancy test; abstains from breastfeeding for at least 30 days after study intervention; and their medical history; their menstrual history, and recent sexual activity has been reviewed Exclusion Criteria: Is clinically unstable-with at least one of the following: hypotensive for age, recent use of intravenous (IV) inotrope and/or IV vasodilator, or recent IV diuretic or oral diuretic dose increase Has a known allergy or sensitivity to vericiguat, any of its constituents, or any other soluble guanylate cyclase (sGC) stimulator Has a history of single ventricle heart disease or has a morphologic systemic right ventricle Has undergone heart transplantation, is awaiting heart transplantation United Network for Organ Sharing (UNOS) Class 1A or equivalent, is receiving continuous IV infusion of an inotrope, or has an implanted ventricular assist device Has sustained or symptomatic dysrhythmia uncontrolled with drug or device therapy Has had recent cardiovascular (CV) surgical procedure or percutaneous intervention to palliate or correct congenital CV malformations Has unoperated or residual hemodynamically significant congenital cardiac malformations Has hypertrophic or restrictive cardiomyopathy Has active myocarditis or has been recently diagnosed with presumed or definitive myocarditis Has severe pulmonary hypertension Requires continuous home oxygen for significant pulmonary disease and/or has known interstitial lung disease Has severe chronic kidney disease Has hepatic disorder such as hepatic encephalopathy, hepatic laboratory abnormalities or Child Pugh Class C Has a gastrointestinal or biliary disorder that could impair absorption, metabolism, or excretion of medications Has concurrent or anticipated concomitant use of phosphodiesterase type 5 inhibitors or an sGC stimulator

Ages Eligible for Study
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Minimum Age: 29 Days
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vericiguat<br>2.5 mg or 5 mg or 10 mg vericiguat administered orally once daily in tablet form for 52 weeks; or 0.2 mg/mL or 1 mg/mL vericiguat administered orally once daily in suspension form for 52 weeks | Drug: Vericiguat tablet<br>* 2.5 mg or 5 mg or 10 mg vericiguat administered orally once daily in tablet form<br>* Other names: MK-1242;Drug: Vericiguat suspension<br>* 0.2 mg/mL or 1 mg/mL vericiguat administered orally once daily in suspension form<br>* Other names: MK-1242;|
| Placebo Comparator: Placebo<br>Placebo for vericiguat administered orally once daily in tablet form for 52 weeks, or administered orally once daily in suspension form for 52 weeks | Drug: Placebo tablet<br>* Placebo for vericiguat administered orally once daily in tablet form<br>* Other names: Placebo for MK-1242;Drug: Placebo suspension<br>* Placebo for vericiguat administered orally once daily in suspension form<br>* Other names: Placebo for MK-1242;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Week 16 in N-terminal pro-brain natriuretic peptide (NT-proBNP) | Change from baseline to Week 16 in log-transformed NT-proBNP | Baseline and Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Week 52 in log-transformed NT-proBNP | Change from baseline to Week 52 in log-transformed NT-proBNP | 1Baseline and Week 52 | 
| First event of cardiovascular (CV) death, heart failure hospitalization (HFH), or worsening of heart failure (HF) without hospitalization | Time from randomization to the first event of CV death, HFH, or worsening of HF without hospitalization | Up to Week 54 | 
| Participants with one or more adverse events (AE) | Percentage of participants with one or more adverse events (AE) | Up to Week 54 | 
| Participants who discontinued study drug due to an AE | Percentage of participants who discontinued study drug due to an AE | Up to Week 52 | 
| Area under the curve from time 0-24 hours post-dose (AUC0-24) of plasma vericiguat | Area under the curve from time 0-24 hours post-dose (AUC0-24) of plasma vericiguat | Pre-dose, 2, 6, 16, 32 and 52 weeks post-dose | 
| Half-life (t1/2) of vericiguat in plasma | t1/2 of vericiguat in plasma | Pre-dose, 2, 6, 16, 32 and 52 weeks post-dose | 
| Oral clearance (CL/F) of plasma vericiguat | CL/F of plasma vericiguat | Pre-dose, 2, 6, 16, 32 and 52 weeks post-dose |