A Phase 2 Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Sotatercept (MK-7962) in Children From 1 to Less Than 18 Years of Age With PAH on Standard of Care
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 42
- 试验地点
- 70
- 主要终点
- Laboratory Parameter (Hematology): Hematocrit
研究概览
简要总结
The primary objectives of the study are to evaluate the safety and tolerability, and pharmacokinetics (PK) of sotatercept over 24 weeks of treatment in children ≥1 to <18 years of age with PAH World Health Organization (WHO) Group 1 on standard of care (SoC). There is no formal hypothesis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented, historic diagnostic right heart catheterization (RHC) any time before Screening confirming the diagnosis of PAH WHO Group 1 in any of the following subtypes:
- •Idiopathic pulmonary arterial hypertension (IPAH)
- •Heritable PAH
- •Drug/toxin-induced PAH
- •PAH associated with connective tissue disease
- •PAH-congenital heart disease (CHD) with shunt closure >6 months before Screening and subsequently confirmed by RHC before Screening
- •PAH with coincidental shunt.
- •Must be on a stable dose(s) of background PAH therapy (phosphdiesterase-5 (PDE5) inhibitors, endothelin receptor antagonists (ERAs), soluble guanylate cyclase stimulators (sGCS), or prostanoids [including subcutaneous and intravenous])
- •If male, agree to the following during the intervention period and for at least 16 weeks (112 days) after the last dose of study intervention:
- •Abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent or
- •Uses contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel's review of the participant's medical records, medical examination, or medical history interview) as detailed below:
- •Uses a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
- •If female, must be either not a WOCBP or use a contraceptive method that is highly effective or be abstinent from heterosexual intercourse during the intervention period and for at least 16 weeks (112 days) after the last dose of study intervention
- •If male, agrees to refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study intervention
- •If female, agrees to refrain from donating blood, eggs, or ovum for the duration of the study and for at least 16 weeks (112 days) after the last dose of study intervention
排除标准
- •History of left-sided heart disease, including valvular disease (eg, moderate or greater mitral or aortic regurgitation or stenosis), left ventricular outflow tract obstruction, and/or left heart failure (eg, restrictive or dilated cardiomyopathy)
- •Severe (as based on the opinion of the investigator) congenital or developmental abnormalities of the lung, thorax, and/or diaphragm
- •History of Eisenmenger syndrome, Potts shunt, or atrial septostomy
- •Unrepaired or residual cardiac shunt
- •Diagnosis of pulmonary veno-occlusive diseases, pulmonary capillary hemangiomatosis, or overt signs of capillary and/or venous involvement
- •PAH associated with portal hypertension
- •Known visceral (lung, liver, or brain) arteriovenous malformation(s)
- •History of full or partial pneumonectomy
- •Untreated more than mild obstructive sleep apnea
- •History of known pericardial constriction
- •Family history of sudden cardiac death or long QT syndrome
- •Any current or prior history of symptomatic coronary disease (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain) within 6 months before Screening
- •Cerebrovascular accident within 3 months before Screening
- •Prior exposure to sotatercept or luspatercept or has had an allergic reaction to any of their excipients
研究组 & 干预措施
Children ≥1 to <18 years old
Participants will receive a subcutaneous (SC) injection every 3 weeks (Q3W) of 0.3 mg/kg. Dosage may be adjusted based on protocol-specific guidelines.
干预措施: Sotatercept (Drug)
结局指标
主要结局
Laboratory Parameter (Hematology): Hematocrit
时间窗: Up to 24 weeks
Hematological parameters will be investigated in blood samples from participants by means of clinical laboratory assays and evaluated by the investigator. The hematocrit will be presented.
Laboratory Parameter (Hematology): Concentration of Hemoglobin
时间窗: Up to 24 weeks
Hematological parameters will be investigated in blood samples from participants by means of clinical laboratory assays and evaluated by the investigator. The concentration of hemoglobin will be presented.
Laboratory Parameter (Hematology): Red Blood Cell (RBC) Count
时间窗: Up to 24 weeks
Hematological parameters will be investigated in blood samples from participants by means of clinical laboratory assays and evaluated by the investigator. The RBC count will be presented.
Serum Trough Concentration (Ctrough) of Sotatercept
时间窗: Predose Day 1, Day 21, Day 42, Day 63, Day 84, Day105, Day 126, Day 147, Day 168, Day 189. Postdose Day 7, Day 14, Day 64, Day 69 and Day 76
Ctrough was the lowest concentration of Sotatercept in serum just before the next dose. Blood samples will be collected at multiple time points to estimate the Ctrough of Sotatercept.
Percentage of Participants Who Experience at Least 1 Adverse Event (AE)
时间窗: Up to 24 weeks
An AE is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The percentage of participants with 1 or more AEs will be assessed.
Area Under the Curve at Steady State (AUCss) of Sotatercept
时间窗: Predose Day 1, Day 21, Day 42, Day 63, Day 84, Day105, Day 126, Day 147, Day 168, Day 189. Postdose Day 7, Day 14, Day 64, Day 69 and Day 76
Blood samples will be collected at multiple time points to estimate the AUCss of Sotatercept.
Area Under the Curve from 0 to 3 weeks (AUC0-3 weeks) of Sotatercept
时间窗: Predose Day 1, Day 7, Day 14, and Predose Day 21
Blood samples will be collected at Predose Day 1, Day 7, Day 14, and Predose Day 21 to estimate the AUC0-3 weeks of Sotatercept.
Percentage of Participants Who Discontinue Study Drug Due to an AE
时间窗: Up to 24 weeks
An AE is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The percentage of participants who discontinued the study drug due to an AE regardless of study completion status will be assessed.
Laboratory Parameter (Hematology): Reticulocyte Count
时间窗: Up to 24 weeks
Hematological parameters will be investigated in blood samples from participants by means of clinical laboratory assays and evaluated by the investigator. The reticulocyte count will be presented.
Laboratory Parameter (Hematology): Platelet Count
时间窗: Up to 24 weeks
Hematological parameters will be investigated in blood samples from participants by means of clinical laboratory assays and evaluated by the investigator. The platelet count will be presented.
Blood Pressure (BP)
时间窗: Up to 24 weeks
BP will be assessed while the participant was seated after a period of rest in a quiet setting with no distractions (eg, television and cell phones).
Titer of Anti-drug Antibody (ADA) to Sotatercept
时间窗: Up to 24 weeks
ADA to Sotatercept will be assessed.
次要结局
- Mean Change from Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE)(Baseline and Week 24)
- Mean Change from Baseline in Pulmonary Artery Systolic Pressure (PASP)(Baseline and Week 24)
- Mean Change from Baseline in 6-Minute Walk Distance (6MWD) (Cohorts 1 and 2)(Baseline and Week 24)
- Mean Change from Baseline in Eccentricity Index(Baseline and Week 24)
- Mean Change from Baseline on Cardiac Output (Cohorts 1 and 2)(Baseline and Week 24)
- Mean Change from Baseline in Right Ventricular Fractional Area Change (RVFAC)(Baseline and Week 24)
- Mean Change from Baseline in Right Ventricular (RV) Function (Cohorts 1 and 2)(Baseline and Week 24)
- Mean Change from Baseline in Pulmonary Arterial Pressure (PAP) (Cohorts 1 and 2)(Baseline and Week 24)
- Mean Change from Baseline in Pediatric Quality of Life (PedsQL) Generic Score(Baseline and Week 24)
- Mean Change from Baseline in N-terminal Prohormone B-type Natriuretic Peptide (NT-proBNP)(Baseline and Week 24)
- Percentage of Participants Who Either Improved or Maintained Their World Health Organization Functional Class (WHO FC)(Baseline and Week 24)