Cytomegalovirus (CMV) infection in pediatric allogeneic HSCT recipients MedDRA version: 20.1 Level: PT Classification code 10011831 Term: Cytomegalovirus infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: PREVYMIS (letermovir)
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: LETERMOVIR
CAS Number: 917389-32-3
Current Sponsor code: MK-8228
Concentration unit: mg milligram(s)
Conc
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. All Age Group 1 participants must have documented positive CMV serostatus (CMV IgG seropositive) for the recipient (R+) within 90 days prior to enrollment. Participants in Age Group 2 and 3 must have documented positive CMV serostatus (CMV IgG seropositive) for the recipient (R+) within 90 days prior to enrollment and/or for the donor (D+); the donor serostatus should be documented within 1 year prior to enrollment. 3. Have undetectable CMV DNA from a plasma or whole blood sample collected within 5 days prior to enrollment. 4. Be within 28 days post-HSCT at the time of enrollment. 5. Participant is aged from birth to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Received a previous allogeneic HSCT (Receipt of a previous autologous HSCT acceptable). 2. History of CMV end-organ disease within 6 months prior to enrollment. 3. Evidence of CMV viremia at any time from either signing of ICF or HSCT procedure, whichever is earlier, until time of enrollment. 4. Suspected or known hypersensitivity to active or inactive ingredients of LET formulations. 5. Severe hepatic insufficiency (defined as Child-Pugh Class C) within 5 days prior to enrollment. 6. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5 x the upper limit of normal (ULN) or serum total bilirubin >2.5 x ULN within 5 days prior to enrollment. 7. Is a) on renal replacement therapy (eg, hemodialysis, peritoneal dialysis) OR b) has end-stage renal impairment with a creatinine clearance =10 mL/min, as calculated by the Cockcroft-Gault equation (for participants =12 years of age) or =10 mL/min/1.73 m2 by the modified Schwartz equation (for participants <12 8. Has both moderate hepatic insufficiency AND moderate-to-severe renal insufficiency. 9. Uncontrolled infection on the day of enrollment. 10. Requires mechanical ventilation or is hemodynamically unstable at the time of enrollment. 11. Has a documented positive result for a 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. 12. Active solid tumor malignancies with the exception of localized basal cell or squamous cell skin cancer or the condition under treatment (eg, lymphomas). 13. 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. Examples of preexisting cardiac conditions that would preclude enrollment include atrial fibrillation and atrial flutter. 14. Received within 7 days prior to enrollment any of the following - ganciclovir, valganciclovir, foscarnet, acyclovir (at doses greater than those recommended for HSV/VZV prophylaxis), valacyclovir (at doses greater than those recommended for HSV/VZV prophylaxis), famciclovir 15. Received within 30 days prior to enrollment 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. 16. Received letermovir at any time prior to enrollment in this study. 17. 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. Participants previously treated with a monoclonal antibody will be eligible to participate after a 28-day washout period. 18. Previously participated in this study or any other study involving LET. 19. 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. 20. Is pregnant or expecting to conceive, is breastfeeding, or plans to
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate letermovir PK in pediatric participants grouped by age.;Secondary Objective: A) To evaluate the safety and tolerability of treatment with letermovir through Week 48 post-transplant based on the proportion of participants with adverse events. B) To evaluate the efficacy of letermovir in prevention of clinically significant CMV infection through Week 14 (~100 days) post-transplant and through Week 24 (~6 months) post-transplant. C) To evaluate the palatability and acceptability of treatment with letermovir oral granules. ;Primary end point(s): 1. Area under the curve from time 0 to 24 hours post-dose (AUC0-24) of plasma letermovir during intensive PK, for participants receiving oral formulation. 2. Maximal concentration (Cmax) of plasma letermovir during intensive PK, for participants receiving oral formulation. 3. Minimum concentration of plasma letermovir observed before next dose (Ctrough) during intensive PK, for participants receiving oral formulation. 4. Area under the curve from time 0 to 24 hours post-dose (AUC0-24) of plasma letermovir, for participants receiving intravenous (IV) formulation. 5. Concentration of plasma letermovir at the end of infusion (Ceoi), for participants receiving IV formulation. 6. Minimum concentration of plasma letermovir observed before next dose (Ctrough) during intensive PK, for participants receiving IV formulation. 7. Minimum concentration of plasma letermovir observed before next dose (Ctrough) during sparse PK, for participants receiving oral formulation. 8. Minimum concentration of plasma letermovir observed before next dose (Ctrough) during sparse PK, for participants receiving IV formulation.;Timepoint(s) of evaluation of this end point: 1. Day 7: Pre-dose, 1, 2. 5, 8, and 24 hours post-dose 2. Day 7: Pre-dose, 1, 2. 5, 8, and 24 hours post-dose 3. Day 7: Pre-dose 4. Weeks 2-14, after 5 consecutive days of administration of IV formulation: Pre-dose, 1, 2. 5, 8, and 24 hours post-dose 5. Weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Percentage of participants with one or more adverse event (AE). 2. Percentage of participants who discontinued study medication due to an AE. 3. Percentage of participants with clinically significant CMV infection (CS-CMVi) through Week 14 post-transplant. 4. Percentage of participants with CS-CMVi through Week 24 post-transplant. 5. Score on a palatability scale for participants receiving oral granules. ;Timepoint(s) of evaluation of this end point: 1. Up to Week 48 post-transplant 2. Up to Week 14 post-transplant 3. Through Week 14 post-transplant 4. Through Week 24 post-transplant 5. On the first and 8th day of administration of oral formulation (up to Week 14 post-transplant) | — |
Countries
Australia, Colombia, France, Germany, Israel, Japan, Mexico, Poland, Spain, Turkey, United States
Contacts
Public ContactGlobal Clinical Trial Operations
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
Outcome results
None listed