A Phase 2b Open-label, Single-arm Study to Evaluate Pharmacokinetics, Efficacy, Safety and Tolerability of Letermovir in Pediatric Participants From Birth to Less Than 18 Years of Age at Risk of Developing CMV Infection and/or Disease Following Allogeneic Haematopoietic Stem Cell Transplantation (HSCT)

Merck Sharp & Dohme LLC40 个研究点分布在 11 个国家目标入组 65 人开始时间: 2019年8月8日最近更新: 2024年8月22日

适应症

干预措施

试验速览

阶段: 2 期
状态: 已完成
发起方: Merck Sharp & Dohme LLC
入组人数: 65
试验地点: 40
主要终点: Minimum Concentration of Plasma Letermovir Observed Before Next Dose (Ctrough) Taken as Oral Formulation by Ages 2 - <18 Years

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The primary objective of this study is to evaluate the pharmacokinetics (PK) of letermovir (LET) in pediatric participants. Participants will be enrolled in the following 3 age groups: Age Group 1: From 12 to <18 years of age (adolescents); Age Group 2: From 2 to <12 years of age (children); and Age Group 3: From birth to <2 years of age (neonates, infants and toddlers). All participants will receive open label LET for 14 weeks (~100 days) post-transplant, with doses based on body weight and age.

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
主要目的: Prevention
盲法: None

入排标准

年龄范围: — 至 17 Years（Child）
性别: All
接受健康志愿者: 否

入选标准

•All participants 12 to <18 years old must have documented positive CMV serostatus (CMV IgG seropositive) for the recipient (R+) within 90 days prior to enrollment. Participants from birth to <12 years old must have documented positive CMV serostatus (CMV IgG seropositive) for the recipient (R+) within 90 days prior to enrollment and/or the donor (D+); the donor serostatus should be documented within 1 year prior to enrollment.
•Is the recipient of a first allogeneic HSCT (bone marrow, peripheral blood stem cell, or cord blood transplant).
•Has undetectable CMV DNA from a plasma or whole blood sample collected within 5 days prior to enrollment.
•Is within 28 days post-HSCT at the time of enrollment.
•Females are not pregnant, not breastfeeding,and is not a woman of childbearing potential (WOCBP); or is a WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 28 days after the last dose of study intervention.
•Participants from 2 to <18 years of age must not be on concomitant Cyclosporin A (CsA), and must be able to take LET tablets or the oral granules (either by mouth or via G tube/NG tube), provided the participant does not have a condition that may interfere with the absorption of oral medication (e.g. vomiting, diarrhea, or a malabsorptive condition) from the day of enrollment until the intensive PK sampling is completed in these participants.
•For participants 2 <12 years old their weight should be at least 10 kg; for participants from birth to <2 years old their weight should be at least 2.5 kg and less than or equal to 15 kg at the time of enrollment.

排除标准

•Has received a previous allogeneic HSCT (Note: receipt of a previous autologous HSCT is acceptable).
•Has a history of CMV end-organ disease within 6 months prior to enrollment.
•Has evidence of CMV viremia at any time from either signing of the ICF or the HSCT procedure, whichever is earlier, until the time of enrollment.
•Has suspected or known hypersensitivity to active or inactive ingredients of LET formulations.
•Has severe hepatic insufficiency within 5 days prior to enrollment.
•Is a) on renal replacement therapy (eg, hemodialysis, peritoneal dialysis) OR b) has end-stage renal impairment.
•Has both moderate hepatic insufficiency and moderate-to-severe renal insufficiency.
•Has an uncontrolled infection on the day of enrollment.
•Requires mechanical ventilation or is hemodynamically unstable at the time of enrollment.
•Has a documented positive result for a human immunodeficiency virus antibody (HIVAb) test at any time prior to enrollment, or for hepatitis C virus antibody (HCV-Ab) with detectable HCV RNA, or hepatitis B surface antigen (HBsAg) within 90 days prior to enrollment.
•Has active solid tumor malignancies with the exception of localized basal cell or squamous cell skin cancer or the condition under treatment (e.g. lymphomas).
•Has a preexisting cardiac condition a) for which the patient is currently being treated or b) which required hospitalization within the last 6 months or c) that may be expected to recur during the course of the trial.
•Has received within 7 days prior to screening any of the following: ganciclovir; valganciclovir; foscarnet; acyclovir; valacyclovir; famciclovir.
•Has received within 30 days prior to screening of any of the following: cidofovir; CMV immunoglobulin; any investigational CMV antiviral agent/biologic therapy; Rifampin and other strong inducers (such as phenytoin, carbamazepine, St John's wort (Hypericum perforatum), rifabutin and phenobarbital) and moderate inducers such as nafcillin, thioridazine, modafinil and bosentan.
•Has received LET at any time prior to enrollment in this study.
•Is currently participating or has participated in a study with an unapproved investigational compound or device within 28 days, or 5X half-life of the investigational compound (excluding monoclonal antibodies), whichever is longer, of initial dosing in this study.
•Has previously participated in this study or any other study involving LET.
•Has previously participated or is currently participating in any study involving administration of a CMV vaccine or another CMV investigational agent, or is planning to participate in a study of a CMV vaccine or another CMV investigational agent during the course of this study.
•Is pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from the time of consent through 28 days after the last dose of study intervention.
•Is expecting to donate eggs starting from the time of consent through 28 days after the last dose of study intervention.
•Has clinically relevant drug or alcohol abuse within 12 months of screening that may interfere with participant treatment, assessment, or compliance with the protocol, as assessed by the investigator.

研究组 & 干预措施

Letermovir

Experimental

Letermovir administered either orally or intravenously within 28 days post-transplant, once daily through week 14 (approximately 100 days). Dosing will vary based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.

干预措施: Letermovir oral granules (Drug)

Letermovir

Experimental

干预措施: Letermovir tablet (Drug)

Letermovir

Experimental

干预措施: Letermovir intravenous (Drug)

结局指标

主要结局

Minimum Concentration of Plasma Letermovir Observed Before Next Dose (Ctrough) Taken as Oral Formulation by Ages 2 - <18 Years

时间窗: Day 7: 24 hours post-dose

Blood was collected on treatment Day 7 from participants aged 2 - \<18 years in order to determine the Ctrough of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged \< 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion.

AUC0-24 of Plasma Letermovir Taken as Oral Formulation by Ages <2 Years