Vericiguat for Heart Failure

Recruiting at 99 trial locations

Overseen By Toll Free Number

Age: < 18

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Phosphodiesterase inhibitors, sGC stimulators

Disqualifiers: Unstable heart failure, Severe kidney disease, Hepatic disorder, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

342 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but it does require that you are on stable medical therapy for heart failure. You cannot use phosphodiesterase type 5 inhibitors or another sGC stimulator while participating.

What data supports the effectiveness of the drug Vericiguat for heart failure?

Vericiguat is effective for treating chronic heart failure with reduced ejection fraction, as shown in the VICTORIA trial, where it reduced the risk of heart failure hospitalization or cardiovascular death compared to a placebo. It is generally well-tolerated, with the most common side effect being low blood pressure. ^{1 2 3 4 5}

Is Vericiguat safe for humans?

Vericiguat is generally well tolerated in humans, with the most common side effect being low blood pressure (hypotension). Other side effects like fainting (syncope) occur at low rates similar to those in people taking a placebo. ^{1 3 4 5 6}

What makes the drug Vericiguat unique for treating heart failure?

Vericiguat is unique because it is the first oral soluble guanylate cyclase (sGC) stimulator approved for treating chronic heart failure with reduced ejection fraction, helping to reduce the risk of cardiovascular death and heart failure hospitalization. It works by enhancing the heart's ability to pump blood, especially in patients who have recently experienced a worsening of their condition. ^{1 3 5 6 7}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for pediatric patients with heart failure due to left ventricular systolic dysfunction who are on stable heart failure medication, have a systemic left ventricle, and an ejection fraction below 45%. Participants must not be pregnant or breastfeeding and use effective contraception if applicable. Exclusions include recent cardiovascular procedures, significant congenital cardiac malformations, severe pulmonary hypertension or kidney disease, liver disorders, clinical instability requiring intensive treatment, known allergies to vericiguat or similar drugs.

Inclusion Criteria

My heart has two working chambers with the main pumping chamber being on the left.

I am on a stable treatment plan for heart failure.

I have a history of heart failure due to weak heart muscle pumping.

Exclusion Criteria

I have been unstable with low blood pressure or needed strong heart or blood pressure medications recently.

I recently had heart surgery to fix a birth defect.

I have a stomach or bile duct condition that affects how my body handles medicine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Base Period

Participants receive vericiguat or placebo for 52 weeks to evaluate efficacy, safety, and pharmacokinetics

52 weeks

Regular visits at pre-dose, 2, 6, 16, 32, and 52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension Period

Participants may opt into continuation of vericiguat treatment long-term

Up to 8 years

Treatment Details

Interventions

• Placebo suspension
• Placebo tablet
• Vericiguat suspension
• Vericiguat tablet

Trial Overview The study tests the effectiveness of Vericiguat (in suspension/tablet form) compared to a placebo in reducing NT-proBNP levels at Week 16 in children with heart failure. The primary goal is to see if Vericiguat can better decrease these biomarker levels indicative of heart stress than a non-active placebo.

Participant Groups

Group I: Extension Period: Vericiguat Experimental Treatment 2 Interventions

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.

Group II: Base Period: Vericiguat Experimental Treatment 2 Interventions

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.

Group III: Base Period: Placebo Placebo Group 2 Interventions

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.

Vericiguat suspension is already approved in United States, European Union for the following indications:

Approved in United States as Verquvo for:

• Heart failure with reduced ejection fraction (HFrEF)

Approved in European Union as Verquvo for:

• Chronic heart failure with reduced ejection fraction (HFrEF)

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a study involving 74 patients with chronic coronary syndromes, vericiguat did not cause any clinically significant prolongation of the QT interval, which is important for heart rhythm safety.

The adverse effects of vericiguat were consistent with its intended action, and the study found no safety concerns, indicating it is a well-tolerated treatment option for patients with chronic heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vericiguat: A Randomized, Phase Ib, Placebo-Controlled, Double-Blind, QTc Interval Study in Patients with Chronic Coronary Syndromes. Böttcher, M., Düngen, HD., Corcea, V., et al.[2023]

In the VICTORIA trial, vericiguat showed a significant reduction in heart failure hospitalizations or cardiovascular death, but the study found that both vericiguat and placebo led to similar improvements in left ventricular (LV) structure and function after 8 months, indicating that the benefits of vericiguat may not be solely due to reverse LV remodeling.

The study included 419 patients with heart failure with reduced ejection fraction (HFrEF) and demonstrated a trend towards a lower rate of the primary composite endpoint in the vericiguat group compared to placebo, suggesting potential clinical benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of vericiguat on left ventricular structure and function in patients with heart failure with reduced ejection fraction: The VICTORIA echocardiographic substudy. Pieske, B., Pieske-Kraigher, E., Lam, CSP., et al.[2023]

In a study involving 32 healthy male volunteers, the co-administration of vericiguat and sildenafil was found to be safe and well-tolerated, with only mild to moderate adverse events reported.

The combination resulted in a minimal decrease in seated blood pressure (≤ 5.4 mmHg) and did not significantly affect the pharmacokinetics of vericiguat, indicating that sildenafil can be safely used alongside vericiguat without major interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Influence of Sildenafil on the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Vericiguat in Healthy Adults. Boettcher, M., Nowotny, B., Krausche, R., et al.[2023]

Vericiguat is the first drug approved specifically for treating symptomatic patients with chronic heart failure with reduced ejection fraction (HFrEF), aimed at reducing the frequency of worsening heart failure episodes.

The article reviews the drug's design, efficacy, and ongoing clinical trials, highlighting its importance in a field with limited treatment options for patients experiencing repeated hospitalizations due to heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of vericiguat: The first soluble guanylate cyclase (sGC) stimulator launched for heart failure with reduced ejection fraction (HFrEF). Xia, J., Hui, N., Tian, L., et al.[2022]

In the phase III VICTORIA trial, vericiguat significantly reduced the risk of death from cardiovascular causes or first hospitalization for heart failure compared to placebo in adults with chronic heart failure with reduced ejection fraction (HFrEF).

Vericiguat was generally well tolerated, with hypotension being the most common treatment-related adverse event, indicating it is a safe and effective option for managing chronic HFrEF, especially after recent worsening events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vericiguat: A Review in Chronic Heart Failure with Reduced Ejection Fraction. Kang, C., Lamb, YN.[2022]

The phase 3 VICTORIA clinical trial showed that vericiguat significantly reduces the risk of cardiovascular death and heart failure hospitalizations in adults with chronic heart failure and an ejection fraction less than 45%.

Vericiguat provides a new treatment option for patients at risk of rehospitalization or those who do not tolerate existing heart failure therapies, demonstrating both safety and efficacy in managing chronic heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vericiguat: A Novel Oral Soluble Guanylate Cyclase Stimulator for the Treatment of Heart Failure. Campbell, N., Kalabalik-Hoganson, J., Frey, K.[2022]

Vericiguat was tested in a study involving patients with heart failure and reduced ejection fraction, showing significant efficacy in improving clinical outcomes compared to placebo.

The results suggest that vericiguat can be a beneficial treatment option for patients with this type of heart failure, potentially enhancing their quality of life and reducing hospitalizations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vericiguat reduced a composite of CV death or HF hospitalization in patients with HF and reduced LVEF. Averbuch, T., Van Spall, HGC.[2020]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Vericiguat: A Randomized, Phase Ib, Placebo-Controlled, Double-Blind, QTc Interval Study in Patients with Chronic Coronary Syndromes. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Effect of vericiguat on left ventricular structure and function in patients with heart failure with reduced ejection fraction: The VICTORIA echocardiographic substudy. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of the Influence of Sildenafil on the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Vericiguat in Healthy Adults. [2023]

4. France pubmed.ncbi.nlm.nih.gov

Development of vericiguat: The first soluble guanylate cyclase (sGC) stimulator launched for heart failure with reduced ejection fraction (HFrEF). [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Vericiguat: A Review in Chronic Heart Failure with Reduced Ejection Fraction. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Vericiguat: A Novel Oral Soluble Guanylate Cyclase Stimulator for the Treatment of Heart Failure. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Vericiguat reduced a composite of CV death or HF hospitalization in patients with HF and reduced LVEF. [2020]