Letermovir Treatment in Pediatric Participants Following Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) (MK-8228-030)
Condition: Cytomegalovirus (CMV) Infection
MeSH terms: Infections; Cytomegalovirus Infections
Intervention: Letermovir oral granules; Letermovir tablet; Letermovir intravenous
Intervention description: Granules administered orally based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.; Tablet administered orally based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.; Letermovir administered intravenously based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
Intervention MeSH terms: Letermovir
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 65.0
Sex: All
Maximum age: 17 Years
Healthy volunteers: No

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.
    

Eligibility 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.