Prenatal Treatment of Congenital Cytomegalovirus Infection With Letermovir Randomized Against Valaciclovir - STEP 1
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Concentrations reached in fetal blood relative to EC50 of letermovir.
研究概览
简要总结
In the model of the perfused cotyledon, Letermovir crosses the placenta to reach appropriate fetal concentration. The cotyledon model can only be performed in the third trimester placenta. Although it is probable that the transplacental passage in the second trimester is in the same range than the one found in the 2th trimester, it needs to be confirmed. The study will be divided in 2 steps: step 1 will study the Letermovir transplacental transfer in the second trimester and step 2 will test the efficacy of letermovir to inhibit replication in infected fetuses.
Main objective To measure the Letermovir transplacental transfer in the second trimester and its accumulation in the amniotic fluid and the placenta in the second trimester
Primary end point:
Concentrations reached in fetal blood relative to EC50 of letermovir.
详细描述
The eligible population of step 1 will be pregnant women in their second trimester of pregnancy and undergoing TOP for any fetal abnormality and no evidence of placental dysfunction.
Letermovir (LTM) is a new anti CMV drug, manufactured by Merck that:
- is highly efficient in vitro against CMV (more than ganciclovir the gold standard drug)
- is as efficient as valganciclovir to cure CMV infection and highly efficient as a prophylaxis to avoid CMV infection and disease in bone marrow transplated patients
- is very well tolerated
- has no data from the use in pregnant women and animal studies are insufficient with respect to fetotoxicity, but no specific concern in pregnant women arises from its safety profile
- crosses the placenta in the ex vivo model of the human perfused cotyledon to reach efficient fetal concentration
In this STEP 1 study, we elected to test 2 Letermovir dosages:
- 240 mg given orally once a day. Based on 10% rate of letermovir transplacental passage as demonstrated in the cotyledonon model, we calculated that the dosage of 240 mg given once a day to the pregnant woman should be suffisent to reach efficient concentration in fetal blood.
- 480 mg /day given orally once a day. 480 mg per day is the recommended dose to prevent CMV infection in bone marrow transplanted patients;
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Pregnant woman ≥ 18 years old
- •in her second trimester of pregnancy
- •undergoing TOP for any fetal abnormality
- •no evidence of placental dysfunction.
- •- affiliation to a social security regime//health insurance
- •given consent for the study.
- •patient must be able and willing to comply with study visits and procedures
排除标准
- •Participation to another interventional drug trial (category 1)
- •Subject protected by law under guardianship or curatorship
- •Woman with creatinine clearance <75 ml/mn/1.73m2
- •Woman with liver insufficiency (Child Pugh grade C), AST, ALT 5 x ULN, bilirubin 2 x ULN.
- •Woman with known allergy to Letermovir
- •Contraindication for the administration of Letermovir listed in the SmPC of Prevymis®
- •Woman treated by pimozide, ergot alkaloids, dabigatran, atorvastatin, simvastatin, rosuvastatin, pitavastatine or cyclosporine.
- •Concomitant administration of millepertuis
- •Woman with hereditary intolerance to galactose, with lactose lapp deficiency, glucose or galactose malabsorption syndrome
研究组 & 干预措施
letermovir
Maternal administration of 1 tablet of Letermovir (240 mg or 480 mg /day) during 3 days before TOP
干预措施: Letermovir (Drug)
结局指标
主要结局
Concentrations reached in fetal blood relative to EC50 of letermovir.
时间窗: At termination of pregnancy, on average 3 days after inclusion
次要结局
未报告次要终点