Clinical Trial of a MEK Inhibitor for RASopathy-Associated Severe Infantile Hypertrophic Cardiomyopathy: Baby MERIT
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 25
- 主要终点
- Time to first occurrence of death, heart transplantation, or LV septal myectomy to relieve LV outflow tract obstruction
研究概览
简要总结
This project seeks to perform a Phase 3 clinical trial to test whether an FDA-approved cancer drug called trametinib is effective in treating young infants with genetic conditions called RASopathies and a severe, life-threatening heart problem called hypertrophic cardiomyopathy. The purpose of this research is to demonstrate that trametinib is effective in preventing these sick babies from dying, receiving a heart transplant or undergoing heart surgery to remove extra heart muscle over a one-year period. In addition, the investigators will determine how often this heart problem comes back when the trametinib treatment is stopped.
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
盲法说明
Echocardiographic studies will be reviewed centrally by the Echocardiography Core Laboratory at Boston Children's Hospital under a workflow that blinds the reader to treatment assignment and participant identity.
入排标准
- 年龄范围
- 28 Days 至 6 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Molecular genetic diagnosis of a RASopathy signaling through the RAS/MAPK pathway as identified by molecular assays performed in a Clinical Laboratory Improvements of 1988 (CLIA) or similarly certified laboratories. Qualifying genotypes will included variants in any gene causing Noonan, Costello or cardiofaciocutaneous syndrome curated as pathogenic or likely pathogenic and consistent with the genetic mechanism (i.e., one allele in genes acting in an autosomal dominant manner and two alleles in trans for the autosomal recessive form of LZTR1-related Noonan syndrome).
- •Diagnosis of HCM, as defined by LV and interventricular septal wall thickness with a z-score > 2 by echocardiography
- •Age ≥ 28 days and ≤ 6 months
- •Ross classification of HF of III or IV
- •Hospitalization
- •In the opinion of the site investigator, ability to comply with study protocol requirements
- •Signed informed consent for the trial by a parent or legal guardian
排除标准
- •PTPN11 pathogenic/likely pathogenic variants causing NSML
- •Prior treatment with a MEK inhibitor
- •Requiring treatment with strong inhibitors of CYP2C19 and CYP3A4, strong inducers of CYP3A4, and substrates of CYP2C9 with a narrow therapeutic index
- •Platelet count < 50,000/µL
- •Neoplastic disorder requiring treatment (e.g., juvenile myelomonocytic leukemia)
研究组 & 干预措施
Treatment
干预措施: Trametinib (Drug)
结局指标
主要结局
Time to first occurrence of death, heart transplantation, or LV septal myectomy to relieve LV outflow tract obstruction
时间窗: From qualifying hospital admission through 12 months after the qualifying hospital admission
This is a composite time-to-event outcome. An event is defined as the first occurrence of any of the following: death, heart transplantation, or LV septal myectomy to relieve LV outflow tract obstruction. For participants experiencing more than one component event, only the first event contributes to the primary endpoint. Participants who do not experience any component event are censored according to the prespecified analysis rules. The treatment arms will be compared using Kaplan-Meier methods and the log-rank test.
次要结局
- Time from qualifying hospital admission to death(From qualifying hospital admission through 12 months after the qualifying hospital admission)
- Change from baseline in LV posterior wall thickness z-score at 12 months(Baseline and 12 months after qualifying hospital admission)
- Ross class at 12 months(12 months after qualifying hospital admission)
- Change from baseline in log-transformed BNP at 12 months(Baseline and 12 months after qualifying hospital admission)
- Time to first occurrence of death, heart transplantation, or LV septal myectomy to relieve LV outflow tract obstruction(From qualifying hospital admission through 24 months after the qualifying hospital admission)
- Relapse-related (descriptive)(from hospitalization till 24 months of follow-up)
- Trametinib-related adverse events(from hospitalization till 24 months of follow-up)