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.
Brief Title
Efficacy, Safety, and Pharmacokinetics of Vericiguat in Pediatric Participants With Heart Failure Due to Left Ventricular Systolic Dysfunction (MK-1242-036)
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
1-888-577-8839
Central Contact Email
Trialsites@msd.com
Completion Date
Completion Date Type
Estimated
Conditions
Heart Failure
Left Ventricular Systolic Dysfunction
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.
* 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.
Inclusion 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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
17 Years
Minimum Age
29 Days
NCT Id
NCT05714085
Org Class
Industry
Org Full Name
Merck Sharp & Dohme LLC
Org Study Id
1242-036
Overall Status
Recruiting
Phases
Phase 2
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
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)
Primary Outcomes
Outcome Description
The change from baseline to Week 16 of the Base Period in log-transformed NT-proBNP will be reported.
Outcome Measure
Base Period: Change from baseline to Week 16 in N-terminal pro-brain natriuretic peptide (NT-proBNP)
Outcome Time Frame
Baseline and Week 16 of Base Period
Outcome Description
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.
Outcome Measure
Extension Period: Percentage of participants with one or more adverse events (AEs)
Outcome Time Frame
Includes data collected up to a maximum of approximately 8 years
Outcome Description
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.
Outcome Measure
Extension Period: Percentage of participants who discontinued study drug due to an AE
Outcome Time Frame
Includes data collected up to a maximum of approximately 8 years
Secondary Ids
Secondary Id
MK-1242-036
Secondary Id
2022-501238-52-00
Secondary Id
U1111-1275-1768
Secondary Id
2021-004399-33
Secondary Outcomes
Outcome Description
The change from baseline to Week 52 of the Base Period in log-transformed NT-proBNP will be reported.
Outcome Time Frame
Baseline and Week 52 of Base Period
Outcome Measure
Base Period: Change from baseline to Week 52 in log-transformed NT-proBNP
Outcome Description
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.
Outcome Time Frame
Up to Week 54 of Base Period
Outcome Measure
Base Period: First event of cardiovascular (CV) death, heart failure hospitalization (HFH), or worsening of heart failure (HF) without hospitalization
Outcome Description
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.
Outcome Time Frame
Up to Week 54 of Base Period
Outcome Measure
Base Period: Percentage of participants with one or more adverse events (AEs)
Outcome Description
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.
Outcome Time Frame
Up to Week 52 of Base Period
Outcome Measure
Base Period: Percentage of participants who discontinued study drug due to an AE
Outcome Description
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.
Outcome Time Frame
Pre-dose, 2, 6, 16, 32 and 52 weeks post-dose (Base Period)
Outcome Measure
Base Period: Area under the curve from time 0-24 hours post-dose (AUC0-24) of plasma vericiguat
Outcome Description
Blood samples were collected at pre-specified time points pre- and post-dose and used to estimate the t1/2 of vericiguat in plasma.
Outcome Time Frame
Pre-dose, 2, 6, 16, 32 and 52 weeks post-dose (Base Period)
Outcome Measure
Base Period: Half-life (t1/2) of vericiguat in plasma
Outcome Description
Blood samples were collected at pre-specified time points pre- and post-dose and used to estimate the CL/F of vericiguat in plasma.
Outcome Time Frame
Pre-dose, 2, 6, 16, 32 and 52 weeks post-dose (Base Period)
Outcome Measure
Base Period: Oral clearance (CL/F) of plasma vericiguat
Outcome Description
The change from the Extension Period baseline to Week 16 of the Extension Period in log-transformed NT-proBNP will be reported.
Outcome Time Frame
Extension Period Baseline (Study Week 54) and Extension Period Week 16 (Study Week 70)
Outcome Measure
Extension Period: Change from extension period baseline to extension period Week 16 in NT-proBNP
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Maximum Age Number (converted to Years and rounded down)
17
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Daphne Hsu
Investigator Email
dhsu@montefiore.org
Investigator Phone
718-741-2538