Phase 2 Completed N=65 Prevention

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

Cytomegalovirus (CMV) Infection

Source: ClinicalTrials.gov NCT03940586 ↗

Enrolled (actual)

Serious AEs

60.3%

Results posted

Jan 2024

Primary outcomePrimary: Area Under the Concentration-time Curve From Time 0 to 24 Hours Post-dose (AUC0-24) of Plasma Letermovir Taken as Oral Formulation by Ages 2 - <18 Years — 80300; 62900 hr*ng/mL

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.

Outcome Measures

Outcome	Result	p-value
PRIMARY Area Under the Concentration-time Curve From Time 0 to 24 Hours Post-dose (AUC0-24) of Plasma Letermovir Taken as Oral Formulation by Ages 2 - <18 Years	80300; 62900	—
PRIMARY AUC0-24 of Plasma Letermovir Taken as Oral Formulation by Ages 2 to <12 Years	39500	—
PRIMARY AUC0-24 of Plasma Letermovir Taken as Oral Formulation by Ages <2 Years	26200	—
PRIMARY Maximal Concentration (Cmax) of Plasma Letermovir Taken as Oral Formulation by Ages 2 - <18 Years	7410; 10800	—
PRIMARY Cmax of Plasma Letermovir Taken as Oral Formulation by Ages 2 to <12 Years	5500	—
PRIMARY Cmax of Plasma Letermovir Taken as Oral Formulation by Ages < 2 Years	2950	—
PRIMARY Minimum Concentration of Plasma Letermovir Observed Before Next Dose (Ctrough) Taken as Oral Formulation by Ages 2 - <18 Years	845; 171	—
PRIMARY Ctrough of Plasma Letermovir Taken as Oral Formulation by Ages 2 to <12 Years	481	—
PRIMARY Ctrough of Plasma Letermovir Taken as Oral Formulation by Ages < 2 Years	61.7	—
PRIMARY AUC0-24 of Plasma Letermovir Taken as Intravenous (IV) Formulation by Ages 12 - <18 Years	114000	—
PRIMARY AUC0-24 of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years	25300	—
PRIMARY AUC0-24 of Plasma Letermovir Taken as IV Formulation by Ages <2 Years	37300	—
PRIMARY Concentration at the End of Infusion (Ceoi) of Plasma Letermovir Taken as IV Formulation by Ages 12 - <18 Years	30600	—
PRIMARY Ceoi of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years	16800; 8200	—
PRIMARY Ceoi of Plasma Letermovir Taken as IV Formulation by Ages s 2 to <12 Years	8630	—
PRIMARY Ceoi of Plasma Letermovir Taken as IV Formulation by Ages <2 Years	11700	—
PRIMARY Ctrough of Plasma Letermovir Taken as IV Formulation by Ages 12 - <18 Years	709	—
PRIMARY Ctrough of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years	216	—
PRIMARY Ctrough of Plasma Letermovir Taken as IV Formulation by Ages <2 Years	98.3	—
PRIMARY Ctrough of Plasma Letermovir Taken During Sparse PK for Oral Formulation	—	—
PRIMARY Ctrough of Plasma Letermovir Taken During Sparse PK as IV Formulation	—	—
SECONDARY Percentage of Participants With One or More Adverse Event (AE)	100.0; 100.0; 100.0	—
SECONDARY Percentage of Participants Who Discontinued Study Medication Due to an AE.	17.9; 7.4; 12.5	—
SECONDARY Percentage of Participants With Clinically Significant CMV Infection Through Week 14 Post-transplant	20.0; 16.7; 28.5	—
SECONDARY Percentage of Participants With Clinically Significant CMV Infection Through Week 24 Post-transplant	24.0; 25.0; 28.6	—
SECONDARY Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the First Day of Administration of Oral Formulation	0; 3; 0; 1; 5; 3	—
SECONDARY Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the Eighth Day of Administration of Oral Formulation	0; 3; 0; 1; 4; 3	—

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 longe

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Data sourced from ClinicalTrials.gov (NCT03940586). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.