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)

Plain English Summary

Efficacy, Safety, and Pharmacokinetics of Vericiguat in Pediatric Participants With Heart Failure Due to Left Ventricular Systolic Dysfunction (MK-1242-036) is a Phase 3 clinical trial sponsored by Merck Sharp & Dohme LLC studying Heart Failure, Left Ventricular Systolic Dysfunction. This study tests if a medication called vericiguat is effective and safe for children with heart failure. It is for children (over 28 days old and weighing at least 3kg) with symptomatic chronic heart failure due to weakened pumping of the left ventricle. Participants will receive either vericiguat or a placebo (inactive substance) by mouth daily for up to 52 weeks, with regular check-ups. Alternative treatments for pediatric heart failure include other medications, lifestyle changes, and in severe cases, heart transplantation. The trial aims to enroll 342 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Children over 28 days old and weighing at least 3kg with symptomatic chronic heart failure and a weakened left ventricle. Children must be on stable medical therapy for heart failure and have a specific measure of heart function (LVEF <45%) within the last 3 months. Children who are clinically unstable, have known allergies to the study drug or similar medications, or have certain other heart conditions may not be eligible. Females who are pregnant or breastfeeding, or who are of childbearing potential and not using effective contraception, are excluded. This trial is studying Heart Failure, Left Ventricular Systolic Dysfunction, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how well the drug reduces a specific marker in the blood (NT-proBNP) that indicates strain on the heart, suggesting improvement in heart function. The specific primary outcome measures are: Base Period: Change from baseline to Week 16 in N-terminal pro-brain natriuretic peptide (NT-proBNP) (Baseline and Week 16 of Base Period); Extension Period: Percentage of participants with one or more adverse events (AEs) (Includes data collected up to a maximum of approximately 8 years); Extension Period: Percentage of participants who discontinued study drug due to an AE (Includes data collected up to a maximum of approximately 8 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a critical need for effective treatments for heart failure in children, a condition with limited therapeutic options and significant long-term impact. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Heart Failure, Left Ventricular Systolic Dysfunction, where improved treatment options are needed.

Investor Insight

This trial targets the pediatric heart failure market, a specialized area with potential for significant unmet needs, and the results could influence the development of new therapies for this populati Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of vericiguat, and how it compares to current treatments. Participation involves regular clinic visits, blood tests, and taking the study medication (vericiguat or placebo) daily for up to a year. Be prepared for potential side effects and discuss any concerns with the study team promptly. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 342 participants

Interventions

• DRUG: Vericiguat tablet — 2.5 mg or 5 mg or 10 mg vericiguat administered orally once daily in tablet form
• DRUG: Vericiguat suspension — 0.2 mg/mL or 1 mg/mL vericiguat administered orally once daily in suspension form
• DRUG: Placebo tablet — Placebo for vericiguat administered orally once daily in tablet form
• DRUG: Placebo suspension — Placebo for vericiguat administered orally once daily in suspension form

Primary Outcomes

• Base Period: Change from baseline to Week 16 in N-terminal pro-brain natriuretic peptide (NT-proBNP) (Baseline and Week 16 of Base Period)
• Extension Period: Percentage of participants with one or more adverse events (AEs) (Includes data collected up to a maximum of approximately 8 years)
• Extension Period: Percentage of participants who discontinued study drug due to an AE (Includes data collected up to a maximum of approximately 8 years)

Secondary Outcomes

• Base Period: Change from baseline to Week 52 in log-transformed NT-proBNP (Baseline and Week 52 of Base Period)
• Base Period: First event of cardiovascular (CV) death, heart failure hospitalization (HFH), or worsening of heart failure (HF) without hospitalization (Up to Week 54 of Base Period)
• Base Period: Percentage of participants with one or more adverse events (AEs) (Up to Week 54 of Base Period)
• Base Period: Percentage of participants who discontinued study drug due to an AE (Up to Week 52 of Base Period)
• Base Period: 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 (Base Period))

Full Eligibility Criteria

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 Locations

• The Regents of the University of California - Los Angeles (UCLA Pediatrics) ( Site 0002), Los Angeles, California, United States
• Loma Linda University Health System ( Site 0008), San Bernardino, California, United States
• Children's Hospital Colorado ( Site 0012), Aurora, Colorado, United States
• Children's National Medical Center ( Site 0020), Washington D.C., District of Columbia, United States
• Johns Hopkins All Children's Hospital ( Site 0029), St. Petersburg, Florida, United States
• Children's Healthcare of Atlanta - Arthur M. Blank Hospital ( Site 0001), Atlanta, Georgia, United States
• Boston Children's Hospital ( Site 0035), Boston, Massachusetts, United States
• C.S. Mott Children's Hospital ( Site 0033), Ann Arbor, Michigan, United States
• Washington University-Pediatric Cardiology/ St. Louis Children's Hospital ( Site 0006), St Louis, Missouri, United States
• Columbia University Medical Center-Pediatric Cardiology ( Site 0016), New York, New York, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Heart Failure
• Left Ventricular Systolic Dysfunction
• Pediatric Cardiology
• Congenital Heart Disease
• Cardiomyopathy
• Pulmonary Hypertension
• Arrhythmia
• Renal Impairment
• Hepatic Impairment
• Vascular Disease

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