Letermovir Treatment in Pediatric Participants Following Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) (MK-8228-030)

• Status: Recruiting
• Trial end date: 2023-10-18
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Merck Sharp & Dohme Corp.
• Treatments: Letermovir

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.