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

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)

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.

Study Overview

• Status: Completed
• Conditions: Cytomegalovirus (CMV) Infection
• Intervention / Treatment: Drug: Letermovir oral granules; Drug: Letermovir tablet; Drug: Letermovir intravenous

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • The Children s Hospital at Westmead ( Site 0185)
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Lady Cilento Children s Hospital ( Site 0182)
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Royal Childrens Hospital Melbourne ( Site 0181)
• Colombia
  • Antioquia
    • Medellin, Antioquia, Colombia, 050024
      • Instituto De Cancerologia S.A. ( Site 0213)
  • Valle Del Cauca
    • Cali, Valle Del Cauca, Colombia, 760032
      • Fundacion Valle del Lili ( Site 0212)
    • Cali, Valle Del Cauca, Colombia, 760042
      • Centro Medico Imbanaco de Cali S.A ( Site 0211)
• France
  • Paris, France, 75015
    • Hôpital Universitaire Necker Enfants Malades-, Unite d'Immunologie-Hematologie et Rhumatologie Pedi
• Germany
  • Berlin, Germany, 13353
    • Charite Universitaetsmedizin Berlin - Campus-Virchow-Klinikum ( Site 0113)
  • Hamburg, Germany, 20246
    • Universitatsklinikum Hamburg-Eppendorf ( Site 0111)
  • Hessen
    • Frankfurt, Hessen, Germany, 60590
      • Universitaetsklinikum Frankfurt ( Site 0112)
  • Nordrhein-Westfalen
    • Muenster, Nordrhein-Westfalen, Germany, 48149
      • Universitaetsklinikum Muenster ( Site 0114)
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center ( Site 0121)
  • Petah Tikva, Israel, 4920235
    • Schneider Children's Medical Center ( Site 0122)
  • Ramat Gan, Israel, 5265601
    • Pediatric Hemato Oncology Safra Children's Hospital, Sheba Medical Center ( Site 0123)
• Japan
  • Saitama, Japan, 330-8777
    • Saitama Children's Medical Center ( Site 0202)
  • Tokyo, Japan, 157-8535
    • National Center for Child Health and Development ( Site 0201)
• Mexico
  • Distrito Federal
    • Mexico City, Distrito Federal, Mexico, 04530
      • Instituto Nacional de Pediatria ( Site 0224)
    • Mexico City, Distrito Federal, Mexico, 06720
      • Hospital Infantil de Mexico ( Site 0221)
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44340
      • Nuevo Hospital Civil Dr Juan I Menchaca ( Site 0223)
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Hospital Universitario "Dr. Jose Eleuterio Gonzalez" ( Site 0222)
• Poland
  • Dolnoslaskie
    • Wrocław, Dolnoslaskie, Poland, 50-556
      • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckieg-Klinika Transplantacji Szpiku, Onkolog
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-094
      • Szpital Uniwersytecki nr 1 im. Dr. Antoniego Jurasza w Bydgoszczy ( Site 0141)
• Spain
  • Barcelona, Spain, 08025
    • H. de la Santa Creu I Sant Pau ( Site 0155)
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d Hebron ( Site 0154)
  • Madrid, Spain, 28009
    • Hospital Infantil Universitario Nino Jesus ( Site 0151)
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz ( Site 0153)
• Turkey
  • Adana, Turkey, 01130
    • Acibadem Adana Hastanesi ( Site 0162)
  • Antalya, Turkey, 07070
    • Akdeniz University Faculty of Medicine ( Site 0161)
  • Izmir, Turkey, 35040
    • Ege Univ.Tip Fakultesi Cocuk Has ( Site 0163)
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center ( Site 0251)
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County ( Site 0241)
    • San Francisco, California, United States, 94158
      • UCSF Benioff Children's Hospital San Francisco ( Site 0245)
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University Of Chicago School Of Medicine ( Site 0253)
  • Massachusetts
    • Boston, Massachusetts, United States, 02115-5737
      • Boston Children's Hospital ( Site 0243)
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center ( Site 0254)
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Health System ( Site 0252)
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center ( Site 0244)
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC ( Site 0258)
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Center ( Site 0257)
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Childrens Hospital ( Site 0248)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Letermovir; 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.

Drug: Letermovir oral granules; Granules administered orally based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.; Other Names: AIC246; MK-8228; AIC001; Drug: Letermovir tablet; Tablet administered orally based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.; Other Names: AIC246; MK-8228; AIC001; Drug: Letermovir intravenous; Letermovir administered intravenously based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.; Other Names: AIC246; MK-8228; AIC001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Blood was collected on treatment Day 7 from participants aged 2 - <18 years in order to determine the AUC0-24 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.	Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
AUC0-24 of Plasma Letermovir Taken as Oral Formulation by Ages 2 to <12 Years	Blood was collected on treatment Day 7 from participants aged 2 to <12 years in order to determine the AUC0-24 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 and >12 years were not presented as their data analysis resulted in a different measure type and method of dispersion.	Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
AUC0-24 of Plasma Letermovir Taken as Oral Formulation by Ages <2 Years	Blood was collected on treatment Day 7 from participants aged <2 years in order to determine the AUC0-24 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 - <18 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The measure of dispersion is not determined when N <2.	Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Maximal Concentration (Cmax) of Plasma Letermovir Taken as Oral Formulation by Ages 2 - <18 Years	Blood was collected on treatment Day 7 from participants aged 2 - <18 years in order to determine the Cmax 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.	Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Cmax of Plasma Letermovir Taken as Oral Formulation by Ages 2 to <12 Years	Blood was collected on treatment Day 7 from participants aged 2 to <12 years in order to determine Cmax 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 and >12 years were not presented as their data analysis resulted in a different measure type and method of dispersion.	Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Cmax of Plasma Letermovir Taken as Oral Formulation by Ages < 2 Years	Blood was collected on treatment Day 7 from participants aged <2 years in order to determine the Cmax 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 - <18 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The measure of dispersion is not determined when N <2	Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Minimum Concentration of Plasma Letermovir Observed Before Next Dose (Ctrough) Taken as Oral Formulation by Ages 2 - <18 Years	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.	Day 7: 24 hours post-dose
Ctrough of Plasma Letermovir Taken as Oral Formulation by Ages 2 to <12 Years	Blood was collected on treatment Day 7 from participants aged 2 to <12 years in order to determine 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 and >12 years were not presented as their data analysis resulted in a different measure type and method of dispersion.	Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Ctrough of Plasma Letermovir Taken as Oral Formulation by Ages < 2 Years	Blood was collected on treatment Day 7 from participants aged <2 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 - <18 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The measure of dispersion is not determined when N <2.	Day 7: 24 hours post-dose
AUC0-24 of Plasma Letermovir Taken as Intravenous (IV) Formulation by Ages 12 - <18 Years	Blood was collected on treatment Day 7 from participants aged 12 - <18 years in order to determine the AUC0-24 of plasma letermovir for participants receiving IV 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 < 12 years were not presented as their data analysis resulted in a different measure type and method of dispersion.	Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
AUC0-24 of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years	Blood was collected on treatment Day 7 from participants aged 2 to <12 years in order to determine the AUC0-24 of plasma letermovir for participants receiving IV 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 and > 12 years were not presented as their data analysis resulted in a different measure type and method of dispersion.	Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
AUC0-24 of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years	Blood was collected on treatment Day 7 from participants aged 2 to <12 years in order to determine the AUC0-24 of plasma letermovir for participants receiving IV 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. The measure of dispersion is not determined when N <2.	Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
AUC0-24 of Plasma Letermovir Taken as IV Formulation by Ages <2 Years	Blood was collected on treatment Day 7 from participants aged <2 years in order to determine the AUC0-24 of plasma letermovir for participants receiving IV 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. The measure of dispersion is not determined when N <2.	Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Concentration at the End of Infusion (Ceoi) of Plasma Letermovir Taken as IV Formulation by Ages 12 - <18 Years	Blood was collected on treatment Day 7 from participants aged 12 - <18 years in order to determine the Ceoi of plasma letermovir for participants receiving IV formulation. As samples were collected outside the collection window Ceoi for these samples were predicted by using a log linear model .Participants aged < 12 years were not presented as their data analysis resulted in a different measure type and method of dispersion.	Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Ceoi of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years	Blood was collected on treatment Day 7 from participants aged 2 to <12 years in order to determine the Ceoi of plasma letermovir for participants receiving IV formulation. As samples were collected outside the collection window Ceoi for these samples were predicted by using a log linear model. Participants aged < 2 years and > 12 years were not presented as their data analysis resulted in a different measure type and method of dispersion.	Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Ceoi of Plasma Letermovir Taken as IV Formulation by Ages s 2 to <12 Years	Blood was collected on treatment Day 7 from participants aged 2 to <12 years in order to determine the Ceoi of plasma letermovir for participants receiving IV formulation. As samples were collected outside the collection window Ceoi for these samples were predicted by using a log linear model. Participants aged > 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion. A measure of dispersion is not determined when N <2.	Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Ceoi of Plasma Letermovir Taken as IV Formulation by Ages <2 Years	Blood was collected on treatment Day 7 from participants aged <2 years in order to determine the Ceoi of plasma letermovir for participants receiving IV formulation. As samples were collected outside the collection window Ceoi for these samples were predicted by using a log linear model. Participants aged > 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion. A measure of dispersion is not determined when N <2.	Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Ctrough of Plasma Letermovir Taken as IV Formulation by Ages 12 - <18 Years	Blood was collected on treatment Day 7 from participants aged 12 - <18 years in order to determine the Ctrough of plasma letermovir for participants receiving IV 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 < 12 years were not presented as their data analysis resulted in a different measure type and method of dispersion.	Day 7: 24 hours post-dose
Ctrough of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years	Blood was collected on treatment Day 7 from participants aged 2 to <12 years in order to determine the Ctrough of plasma letermovir for participants receiving IV 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 and > 12 years were not presented as their data analysis resulted in a different measure type and method of dispersion.	Day 7: 24 hours post-dose
Ctrough of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years	Blood was collected on treatment Day 7 from participants aged <2 years in order to determine the Ctrough of plasma letermovir for participants receiving IV 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. The measure of dispersion is not determined when N <2.	Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Ctrough of Plasma Letermovir Taken as IV Formulation by Ages <2 Years	Blood was collected on treatment Day 7 from participants aged <2 years in order to determine the Ctrough of plasma letermovir for participants receiving IV 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. The measure type is Geometric Mean, and a measure of dispersion is not determined when N <2.	Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Ctrough of Plasma Letermovir Taken During Sparse PK for Oral Formulation	Blood was collected on treatment Day 7 in order to determine the Ctrough of plasma letermovir during sparse PK 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.	Day 7: 24 hours post-dose
Ctrough of Plasma Letermovir Taken During Sparse PK as IV Formulation	Blood was collected on treatment Day 7 in order to determine the Ctrough of plasma letermovir for participants receiving IV formulation during sparse PK. 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.	Day 7: 24 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With One or More Adverse Event (AE)	.An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The 95% confidence interval (CI) is based on the exact binomial method proposed by Clopper and Pearson.	Up to Week 48 post-transplant (up to 52 weeks)
Percentage of Participants Who Discontinued Study Medication Due to an AE.	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The 95% CI is based on the exact binomial method proposed by Clopper and Pearson.	Up to Week 14 post-transplant (up to 18 weeks)
Percentage of Participants With Clinically Significant CMV Infection Through Week 14 Post-transplant	Clinically significant cytomegalovirus (CMV) infection is defined as CMV end organ disease (proven or probable) or initiation of pre-emptive therapy (PET) based on documented CMV viremia and the clinical condition of the participant. The 95% confidence interval (CI) was based on the exact binomial method proposed by Clopper and Pearson. Missing values: were handled by the Non-Completer=Failure (NC=F) approach. where failure was defined as all participants who developed clinically significant CMV infection or prematurely discontinued from the study or had a missing outcome through week 14 post-transplant visit window.	Up to Week 14 post-transplant (up to 18 weeks)
Percentage of Participants With Clinically Significant CMV Infection Through Week 24 Post-transplant	Clinically significant CMV infection is defined as CMV end organ disease (proven or probable) or initiation of PET based on documented CMV viremia and the clinical condition of the participant. The 95% confidence interval (CI) was based on the exact binomial method proposed by Clopper and Pearson. Missing values: were handled by the Non-Completer=Failure (NC=F) approach. where failure was defined as all participants who developed clinically significant CMV infection or prematurely discontinued from the study or had a missing outcome through week 24 post-transplant visit window.	Up to Week 24 post-transplant (up to 28 weeks)
Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the First Day of Administration of Oral Formulation	Palatability was measured by response to a questionnaire on the taste of medication , with responses from very good, good, neither good nor bad, bad or very bad.	Day 1 of administration of oral formulation up to Week 14 post-transplant (up to 18 weeks)
Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the Eighth Day of Administration of Oral Formulation	Palatability was measured by response to a questionnaire on the taste of medication , with responses from very good, good, neither good nor bad, bad or very bad.	Day 8 of administration of oral formulation up to Week 14 post-transplant (up to 18 weeks)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2019
• Primary Completion (Actual): January 4, 2023
• Study Completion (Actual): August 25, 2023

Study Registration Dates

• First Submitted: May 6, 2019
• First Submitted That Met QC Criteria: May 6, 2019
• First Posted (Actual): May 7, 2019

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; DNA Virus Infections; Herpesviridae Infections; Infections; Cytomegalovirus Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Letermovir
• Other Study ID Numbers: 8228-030; MK-8228-030 (Other Identifier: Merck Protocol Number); 205242 (Registry Identifier: JAPIC-CTI); 2018-001326-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No