Open-Label Extension Study of Vericiguat in Pediatric Patients with Heart Failure Due to Systemic Left Ventricular Systolic Dysfunction

The primary objective of this study is to monitor the **safety** and tolerability of **vericiguat** (MK-1242) in pediatric participants with heart failure due to systemic left ventricular systolic dysfunction. This is clinically relevant as it aims to ensure that the treatment is safe for use in a vulnerable population, potentially leading to improved management of heart failure in children.

Secondary objectives include evaluating the change in NT-proBNP levels from baseline to Week 16. NT-proBNP is a biomarker used to assess the severity of heart failure, and changes in its levels can provide insights into the treatment's efficacy in managing the condition.

The clinical trial involves a total of **155 participants** diagnosed with **heart failure due to systemic left ventricular systolic dysfunction**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on their prior involvement in the VALOR base study, having received at least one dose of the study intervention and completed the Week 52 visit and safety follow-up period. The trial includes individuals who are able to receive medication via the oral or gastric route. The population is characterized by a mix of general health statuses, and it includes a vulnerable population. Lifestyle considerations such as diet, physical activity, and habits were not specified by the sponsor.

The clinical trial is designed as a **Phase 3**, single-arm, open-label extension study to evaluate the safety and tolerability of **vericiguat** in pediatric participants with heart failure due to systemic left ventricular systolic dysfunction. The trial will involve the administration of vericiguat in two pharmaceutical forms: tablet and oral suspension, both intended for oral use. The study is expected to commence recruitment on July 1, 2024, and conclude by April 15, 2032, with a maximum treatment period of 108 weeks for each participant.

Participants eligible for inclusion must have completed the Week 52 visit and safety follow-up period of the VALOR base study, having received at least one dose of the study intervention. The trial will monitor the number of participants experiencing adverse events and those discontinuing treatment due to adverse events as primary endpoints. A secondary endpoint will assess changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels from baseline to Week 16.

The sequence of study visits includes an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor safety and efficacy. The end-of-study visit will conclude the participant's involvement, which is anticipated to last up to 108 weeks. Conditions that may lead to early termination from the study include noncompliance with the study protocol or adverse events related to the study drug.

The clinical trial involves the administration of **Vericiguat**, a pharmaceutical product developed by Merck & Co. Inc. The experimental medication is available in two pharmaceutical forms: **tablet** and **oral suspension**. The active substance in both forms is vericiguat, a chemical compound also known by its synonyms BAY 1021189 and MK-1242. The **tablet** form is not a pediatric formulation and is administered orally. The maximum daily dose for the tablet form is 10 mg, with a total maximum dose of 33 g over a treatment period of up to 108 days. The **oral suspension** form is specifically designed as a pediatric formulation, also administered orally, with the same dosing parameters as the tablet form.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on monitoring the safety and tolerability of vericiguat in pediatric participants with heart failure due to systemic left ventricular systolic dysfunction. The trial is a Phase 3, single-arm, open-label extension of the Vericiguat VALOR study, known as VALOR EXT. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen.

Efficacy in the clinical trial will be assessed using specific endpoints designed to evaluate the impact of **vericiguat** on pediatric participants with heart failure due to systemic left ventricular systolic dysfunction. The primary efficacy endpoints include the number of participants who experience an adverse event (AE) and the number of participants who discontinue study treatment due to an AE. These endpoints will provide insight into the safety profile of the treatment.

Secondary efficacy endpoints will focus on the change from baseline to Week 16 in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. This biomarker is a critical indicator of heart failure severity and will be measured to assess the therapeutic effect of **vericiguat**. The collection and analysis of these parameters will be conducted at specified timepoints, ensuring a comprehensive evaluation of the treatment's efficacy over the course of the trial.