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)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 342
- 试验地点
- 109
- 主要终点
- Base Period: Change from baseline to Week 16 in N-terminal pro-brain natriuretic peptide (NT-proBNP)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 29 Days 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Extension Period: Vericiguat
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.
干预措施: Vericiguat suspension (Drug)
Extension Period: Vericiguat
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.
干预措施: Vericiguat tablet (Drug)
Base Period: Placebo
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.
干预措施: Placebo suspension (Drug)
Base Period: Vericiguat
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.
干预措施: Vericiguat suspension (Drug)
Base Period: Vericiguat
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.
干预措施: Vericiguat tablet (Drug)
Base Period: Placebo
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.
干预措施: Placebo tablet (Drug)
结局指标
主要结局
Base Period: Change from baseline to Week 16 in N-terminal pro-brain natriuretic peptide (NT-proBNP)
时间窗: 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)
时间窗: 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
时间窗: 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.
次要结局
- 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))
- Base Period: Half-life (t1/2) of vericiguat in plasma(Pre-dose, 2, 6, 16, 32 and 52 weeks post-dose (Base Period))
- Base Period: Oral clearance (CL/F) of plasma vericiguat(Pre-dose, 2, 6, 16, 32 and 52 weeks post-dose (Base Period))
- 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))