Heart Failure, Left Ventricular Systolic Dysfunction
Conditions
Brief 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.
Detailed 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.
Interventions
2.5 mg or 5 mg or 10 mg vericiguat administered orally once daily in tablet form
DRUGVericiguat suspension
0.2 mg/mL or 1 mg/mL vericiguat administered orally once daily in suspension form
DRUGPlacebo tablet
Placebo for vericiguat administered orally once daily in tablet form
Placebo for vericiguat administered orally once daily in suspension form
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
29 Days to 17 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Base Period: Change from baseline to Week 16 in N-terminal pro-brain natriuretic peptide (NT-proBNP) | Baseline and Week 16 of Base Period | The change from baseline to Week 16 of the Base Period in log-transformed NT-proBNP will be reported. |
| Extension Period: Percentage of participants with one or more adverse events (AEs) | Includes data collected up to a maximum of approximately 8 years | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants with one or more AEs in the Extension Period will be reported. |
| Extension Period: Percentage of participants who discontinued study drug due to an AE | Includes data collected up to a maximum of approximately 8 years | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study drug in the Extension Period due to an AE will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Base Period: Change from baseline to Week 52 in log-transformed NT-proBNP | Baseline and Week 52 of Base Period | The change from baseline to Week 52 of the Base Period in log-transformed NT-proBNP will be reported. |
| 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 | The time from randomization to the first event of CV death, HFH, or worsening of HF without hospitalization will be reported for the Base Period. |
| Base Period: Percentage of participants with one or more adverse events (AEs) | Up to Week 54 of Base Period | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants with one or more AEs in the Base Period will be reported. |
| Base Period: Percentage of participants who discontinued study drug due to an AE | Up to Week 52 of Base Period | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study drug in the Base Period due to an AE will be reported. |
| 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) | Blood samples were collected at pre-specified time points pre- and post-dose and used to estimate the area under the curve from time 0-24 hours post-dose (AUC0-24) of plasma vericiguat. |
| Base Period: Half-life (t1/2) of vericiguat in plasma | Pre-dose, 2, 6, 16, 32 and 52 weeks post-dose (Base Period) | Blood samples were collected at pre-specified time points pre- and post-dose and used to estimate the t1/2 of vericiguat in plasma. |
| Base Period: Oral clearance (CL/F) of plasma vericiguat | Pre-dose, 2, 6, 16, 32 and 52 weeks post-dose (Base Period) | Blood samples were collected at pre-specified time points pre- and post-dose and used to estimate the CL/F of vericiguat in plasma. |
| Extension Period: Change from extension period baseline to extension period Week 16 in NT-proBNP | Extension Period Baseline (Study Week 54) and Extension Period Week 16 (Study Week 70) | The change from the Extension Period baseline to Week 16 of the Extension Period in log-transformed NT-proBNP will be reported. |
Countries
Belgium, Brazil, Canada, Colombia, Croatia, Denmark, Finland, France, Germany, Hungary, Ireland, Italy, Malaysia, Mexico, Netherlands, New Zealand, Peru, Poland, Portugal, Serbia, Singapore, South Africa, South Korea, Spain, Sweden, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed