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

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Left Ventricular Systolic Dysfunction; Heart Failure

Treatments: Drug: Placebo tablet; Drug: Placebo suspension; Drug: Vericiguat tablet; Drug: Vericiguat suspension

Study type: Interventional

Funder types: Industry

Identifiers

NCT05714085

MK-1242-036 (Other Identifier)

1242-036

2022-501238-52-00 (Registry Identifier)

2021-004399-33 (EudraCT Number)

Details and patient eligibility

About

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 of the Base Period. The primary hypothesis is that vericiguat is superior to placebo in reducing NT-proBNP at Week 16 of the Base Period.

Full description

As of Protocol Amendment 2, the separate open-label extension arm of study MK-1242-043 (NCT06428383) will be incorporated into the present MK-1242-036 study as an extension period. Participants from the Base Period will be provided the opportunity to participate in the optional open-label Extension Period if eligible. After all ongoing participants are transferred into the extension period of MK-1242-036, MK-1242-043 (NCT06428383) will be formally closed.

Enrollment: 342 estimated patients

Sex: All

Ages: 29 days to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Has 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.
• Is of any sex/gender, from >28 days to <18 years of age inclusive. Must weigh ≥3 kg to participate.
• 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 during the study intervention period and for at least 30 days after study intervention; and their medical history; their menstrual history, and recent sexual activity has been reviewed.
• Extension Period: Was randomized, received at least 1 dose of study intervention (vericiguat or placebo), did not permanently discontinue study intervention, and completed the Week 52 visit and safety follow-up period of the Base Period

Exclusion criteria

• Is clinically unstable-with at least one of the following: has symptomatic hypotension or is hypotensive for age, recent use of intravenous (IV) inotrope and/or IV vasodilator, or recent IV diuretic.
• 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 acute coronary syndrome, undergone recent coronary intervention, or indication for coronary revascularization.
• Has symptomatic carotid stenosis or other symptomatic cerebrovascular disease
• 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 significant bone disease (other than osteopenia) that in the assessment of the investigator can alter bone formation
• Has concurrent or anticipated concomitant use of phosphodiesterase type 5 inhibitors or an sGC stimulator.
• Has received a COVID-19 vaccination within 1 week before randomization.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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342 participants in 3 patient groups, including a placebo group

Base Period: Vericiguat

Experimental group

Description:

Participants in the Base Period receive 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.

Treatment:

Drug: Vericiguat suspension

Drug: Vericiguat tablet

Base Period: Placebo

Placebo Comparator group

Description:

Participants in the Base Period receive placebo for vericiguat administered orally once daily in tablet form for 52 weeks, or administered orally once daily in suspension form for 52 weeks.

Treatment:

Drug: Placebo suspension

Drug: Placebo tablet

Extension Period: Vericiguat

Experimental group

Description:

Participants in the Extension Period receive either 2.5 mg or 5 mg or 10 mg vericiguat administered orally once daily in tablet form; or 0.2 mg/mL or 1 mg/mL vericiguat administered orally once daily in suspension form; following completion of the Base Period.

Treatment:

Drug: Vericiguat suspension

Drug: Vericiguat tablet