Letermovir Treatment in Pediatric Participants Following Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) (MK-8228-030)
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| ClinicalTrials.gov Identifier: NCT03940586 |
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Recruitment Status :
Recruiting
First Posted : May 7, 2019
Last Update Posted : September 17, 2021
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Sponsor:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
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Brief 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Cytomegalovirus (CMV) Infection | Drug: Letermovir oral granules Drug: Letermovir tablet Drug: Letermovir intravenous | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 60 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Prevention |
| Official 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) |
| Actual Study Start Date : | August 8, 2019 |
| Estimated Primary Completion Date : | February 21, 2023 |
| Estimated Study Completion Date : | October 18, 2023 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Letermovir
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Letermovir oral granules
Granules administered orally based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
Other Names:
Drug: Letermovir tablet Tablet administered orally based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
Other Names:
Drug: Letermovir intravenous Letermovir administered intravenously based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
Other Names:
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Primary Outcome Measures :
- Area under the concentration-time curve of plasma letermovir for oral formulation [ Time Frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose ]Area under the curve from time 0 to 24 hours post-dose (AUC0-24) of plasma letermovir during intensive pharmacokinetics (PK), for participants receiving oral formulation.
- Maximal concentration of plasma letermovir for oral formulation [ Time Frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose ]Maximal concentration (Cmax) of plasma letermovir during intensive PK, for participants receiving oral formulation.
- Minimum concentration of plasma letermovir observed before next dose for oral formulation [ Time Frame: Day 7: Pre-dose ]Minimum concentration of plasma letermovir observed before next dose (Ctrough) during intensive PK, for participants receiving oral formulation.
- Area under the concentration-time curve of plasma letermovir for intravenous formulation [ Time Frame: After 5 consecutive days of administration of intravenous formulation: Pre-dose, 1, 2.5, 8, and 24 hours post-dose (up to 14 weeks) ]Area under the curve from time 0 to 24 hours post-dose (AUC0-24) of plasma letermovir, for participants receiving intravenous (IV) formulation.
- Concentration at the end of infusion of plasma letermovir for IV formulation [ Time Frame: After 5 consecutive days of administration of IV formulation: 1 hour post-dose (up to 14 weeks) ]Concentration of plasma letermovir at the end of infusion (Ceoi), for participants receiving IV formulation.
- Minimum concentration of plasma letermovir observed before next dose for IV formulation [ Time Frame: After 5 consecutive days of administration of IV formulation: Pre-dose (up to 14 weeks) ]Minimum concentration of plasma letermovir observed before next dose (Ctrough) during intensive PK, for participants receiving IV formulation.
- Minimum concentration of plasma letermovir observed before next dose during sparse PK for oral formulation [ Time Frame: Pre-dose on Weeks 2, 4, 6, 8, 12, 14 ]Minimum concentration of plasma letermovir observed before next dose (Ctrough) during sparse PK, for participants receiving oral formulation.
- Minimum concentration of plasma letermovir observed before next dose during sparse PK for IV formulation [ Time Frame: Pre-dose on Weeks 2, 4, 6, 8, 12, 14 ]Minimum concentration of plasma letermovir observed before next dose (Ctrough) during sparse PK, for participants receiving IV formulation.
Secondary Outcome Measures :
- Participants with an adverse event [ Time Frame: Up to Week 48 post-transplant (up to 52 weeks) ]Percentage of participants with one or more adverse event (AE).
- Participants who discontinued study medication [ Time Frame: Up to Week 14 post-transplant (up to 18 weeks) ]Percentage of participants who discontinued study medication due to an AE.
- Participants with clinically significant CMV infection through Week 14 post-transplant [ Time Frame: Up to Week 14 post-transplant (up to 18 weeks) ]Percentage of participants with clinically significant CMV infection (CS-CMVi) through Week 14 post-transplant
- Participants with clinically significant CMV infection through Week 24 post-transplant [ Time Frame: Up to Week 24 post-transplant (up to 28 weeks) ]Percentage of participants with clinically significant CMV infection (CS-CMVi) through Week 24 post-transplant
- Score on a palatability scale for participants receiving oral granules. [ Time Frame: On the first and eighth day of administration of oral formulation up to Week 14 post-transplant (up to 18 weeks) ]Palatability was measured by a facial hedonic scale (FHS), a five point facial expression scale depicting various degrees of pleasure, where a score of 1 indicated disliked very much; ranging to a score of 5 which indicated liked very much.
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| Ages Eligible for Study: | up to 17 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03940586
Contacts
| Contact: Toll Free Number | 1-888-577-8839 | Trialsites@merck.com |
Locations
Show 37 study locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
| Study Director: | Medical Director | Merck Sharp & Dohme Corp. |
| Responsible Party: | Merck Sharp & Dohme Corp. |
| ClinicalTrials.gov Identifier: | NCT03940586 |
| Other Study ID Numbers: |
8228-030 2018-001326-25 ( EudraCT Number ) MK-8228-030 ( Other Identifier: Merck Protocol Number ) 205242 ( Registry Identifier: JAPIC-CTI ) |
| First Posted: | May 7, 2019 Key Record Dates |
| Last Update Posted: | September 17, 2021 |
| Last Verified: | September 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf |
| URL: | http://engagezone.msd.com/ds_documentation.php |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Infection |