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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03940586




Registration number
NCT03940586
Ethics application status
Date submitted
6/05/2019
Date registered
7/05/2019

Titles & IDs
Public title
Letermovir Treatment in Pediatric Participants Following Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) (MK-8228-030)
Scientific title
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)
Secondary ID [1] 0 0
MK-8228-030
Secondary ID [2] 0 0
8228-030
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cytomegalovirus (CMV) Infection 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Letermovir oral granules
Treatment: Drugs - Letermovir tablet
Treatment: Drugs - Letermovir intravenous

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.


Treatment: Drugs: Letermovir oral granules
Granules administered orally based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.

Treatment: Drugs: Letermovir tablet
Tablet administered orally based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.

Treatment: Drugs: Letermovir intravenous
Letermovir administered intravenously based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Primary outcome [2] 0 0
AUC0-24 of Plasma Letermovir Taken as Oral Formulation by Ages 2 to <12 Years
Timepoint [2] 0 0
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Primary outcome [3] 0 0
AUC0-24 of Plasma Letermovir Taken as Oral Formulation by Ages <2 Years
Timepoint [3] 0 0
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Primary outcome [4] 0 0
Maximal Concentration (Cmax) of Plasma Letermovir Taken as Oral Formulation by Ages 2 - <18 Years
Timepoint [4] 0 0
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Primary outcome [5] 0 0
Cmax of Plasma Letermovir Taken as Oral Formulation by Ages 2 to <12 Years
Timepoint [5] 0 0
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Primary outcome [6] 0 0
Cmax of Plasma Letermovir Taken as Oral Formulation by Ages < 2 Years
Timepoint [6] 0 0
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Primary outcome [7] 0 0
Minimum Concentration of Plasma Letermovir Observed Before Next Dose (Ctrough) Taken as Oral Formulation by Ages 2 - <18 Years
Timepoint [7] 0 0
Day 7: 24 hours post-dose
Primary outcome [8] 0 0
Ctrough of Plasma Letermovir Taken as Oral Formulation by Ages 2 to <12 Years
Timepoint [8] 0 0
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Primary outcome [9] 0 0
Ctrough of Plasma Letermovir Taken as Oral Formulation by Ages < 2 Years
Timepoint [9] 0 0
Day 7: 24 hours post-dose
Primary outcome [10] 0 0
AUC0-24 of Plasma Letermovir Taken as Intravenous (IV) Formulation by Ages 12 - <18 Years
Timepoint [10] 0 0
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Primary outcome [11] 0 0
AUC0-24 of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years
Timepoint [11] 0 0
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Primary outcome [12] 0 0
AUC0-24 of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years
Timepoint [12] 0 0
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Primary outcome [13] 0 0
AUC0-24 of Plasma Letermovir Taken as IV Formulation by Ages <2 Years
Timepoint [13] 0 0
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Primary outcome [14] 0 0
Concentration at the End of Infusion (Ceoi) of Plasma Letermovir Taken as IV Formulation by Ages 12 - <18 Years
Timepoint [14] 0 0
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Primary outcome [15] 0 0
Ceoi of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years
Timepoint [15] 0 0
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Primary outcome [16] 0 0
Ceoi of Plasma Letermovir Taken as IV Formulation by Ages s 2 to <12 Years
Timepoint [16] 0 0
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Primary outcome [17] 0 0
Ceoi of Plasma Letermovir Taken as IV Formulation by Ages <2 Years
Timepoint [17] 0 0
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Primary outcome [18] 0 0
Ctrough of Plasma Letermovir Taken as IV Formulation by Ages 12 - <18 Years
Timepoint [18] 0 0
Day 7: 24 hours post-dose
Primary outcome [19] 0 0
Ctrough of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years
Timepoint [19] 0 0
Day 7: 24 hours post-dose
Primary outcome [20] 0 0
Ctrough of Plasma Letermovir Taken as IV Formulation by Ages 2 to <12 Years
Timepoint [20] 0 0
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Primary outcome [21] 0 0
Ctrough of Plasma Letermovir Taken as IV Formulation by Ages <2 Years
Timepoint [21] 0 0
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
Primary outcome [22] 0 0
Ctrough of Plasma Letermovir Taken During Sparse PK for Oral Formulation
Timepoint [22] 0 0
Day 7: 24 hours post-dose
Primary outcome [23] 0 0
Ctrough of Plasma Letermovir Taken During Sparse PK as IV Formulation
Timepoint [23] 0 0
Day 7: 24 hours post-dose
Secondary outcome [1] 0 0
Percentage of Participants With One or More Adverse Event (AE)
Timepoint [1] 0 0
Up to Week 48 post-transplant (up to 52 weeks)
Secondary outcome [2] 0 0
Percentage of Participants Who Discontinued Study Medication Due to an AE.
Timepoint [2] 0 0
Up to Week 14 post-transplant (up to 18 weeks)
Secondary outcome [3] 0 0
Percentage of Participants With Clinically Significant CMV Infection Through Week 14 Post-transplant
Timepoint [3] 0 0
Up to Week 14 post-transplant (up to 18 weeks)
Secondary outcome [4] 0 0
Percentage of Participants With Clinically Significant CMV Infection Through Week 24 Post-transplant
Timepoint [4] 0 0
Up to Week 24 post-transplant (up to 28 weeks)
Secondary outcome [5] 0 0
Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the First Day of Administration of Oral Formulation
Timepoint [5] 0 0
Day 1 of administration of oral formulation up to Week 14 post-transplant (up to 18 weeks)
Secondary outcome [6] 0 0
Number of Participants Receiving Oral Granules With Palatability Response, Based on Taste of Medication on the Eighth Day of Administration of Oral Formulation
Timepoint [6] 0 0
Day 8 of administration of oral formulation up to Week 14 post-transplant (up to 18 weeks)

Eligibility
Key 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.
Minimum age
No limit
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Prevention
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/08/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
25/08/2023
Sample size
Target
Accrual to date
Final
65
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
The Children s Hospital at Westmead ( Site 0185) - Westmead
Recruitment hospital [2] 0 0
Lady Cilento Children s Hospital ( Site 0182) - South Brisbane
Recruitment hospital [3] 0 0
Royal Childrens Hospital Melbourne ( Site 0181) - Parkville
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Washington
Country [10] 0 0
Colombia
State/province [10] 0 0
Antioquia
Country [11] 0 0
Colombia
State/province [11] 0 0
Valle Del Cauca
Country [12] 0 0
France
State/province [12] 0 0
Paris
Country [13] 0 0
Germany
State/province [13] 0 0
Hessen
Country [14] 0 0
Germany
State/province [14] 0 0
Nordrhein-Westfalen
Country [15] 0 0
Germany
State/province [15] 0 0
Berlin
Country [16] 0 0
Germany
State/province [16] 0 0
Hamburg
Country [17] 0 0
Israel
State/province [17] 0 0
Haifa
Country [18] 0 0
Israel
State/province [18] 0 0
Petah Tikva
Country [19] 0 0
Israel
State/province [19] 0 0
Ramat Gan
Country [20] 0 0
Japan
State/province [20] 0 0
Saitama
Country [21] 0 0
Japan
State/province [21] 0 0
Tokyo
Country [22] 0 0
Mexico
State/province [22] 0 0
Distrito Federal
Country [23] 0 0
Mexico
State/province [23] 0 0
Jalisco
Country [24] 0 0
Mexico
State/province [24] 0 0
Nuevo Leon
Country [25] 0 0
Poland
State/province [25] 0 0
Dolnoslaskie
Country [26] 0 0
Poland
State/province [26] 0 0
Kujawsko-pomorskie
Country [27] 0 0
Spain
State/province [27] 0 0
Barcelona
Country [28] 0 0
Spain
State/province [28] 0 0
Madrid
Country [29] 0 0
Turkey
State/province [29] 0 0
Adana
Country [30] 0 0
Turkey
State/province [30] 0 0
Antalya
Country [31] 0 0
Turkey
State/province [31] 0 0
Izmir

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?




Results publications and other study-related documents

TypeCitations or Other Details
Journal Groll AH, Schulte JH, Antmen AB, Fraser CJ, Teal V... [More Details]


Results are available at https://clinicaltrials.gov/study/NCT03940586