Letermovir Versus Valganciclovir to Prevent Human Cytomegalovirus Disease in Kidney Transplant Recipients (MK-8228-002)

Inclusion criteria

• Have a documented negative serostatus for CMV within 180 days prior to randomization.
• Anticipate receiving a primary or secondary allograft kidney from a CMV IgG seropositive (D+) donor at the time of screening AND have received a primary or secondary allograft kidney from a documented D+ donor at the time of randomization.
• Be within 0 (i.e. day of transplantation) to 7 days (inclusive) post-kidney transplant at the time of randomization.
• Males agree to use contraception during the treatment period, and for at least 90 days after the last dose of study treatment, and refrain from donating sperm during this period.
• Female is not pregnant, not breastfeeding, and is not a woman of childbearing potential (WOCBP), OR if a WOCBP, agrees to follow the contraception guidance during the treatment period and for at least 90 days after the last dose of study treatment.

Exclusion criteria

• Has received a previous solid organ transplant or hematopoietic stem cell transplant (HSCT). Note: Participants who have received a prior primary allograft kidney may be enrolled, provided that all other inclusion/exclusion criteria are met.
• Is a multi-organ transplant recipient (e.g. kidney-pancreas). Double kidney transplant recipients (i.e. transplant of two kidneys from the same donor to the same recipient simultaneously) will be excluded.
• Has a history of CMV disease or suspected CMV disease within 6 months prior to randomization.
• Has suspected or known hypersensitivity to active or inactive ingredients of LET formulations, VGCV, GCV, and/or ACV formulations.
• Is on dialysis or plasmapheresis at the time of randomization. Dialysis includes hemofiltration.
• Has Child-Pugh Class C severe hepatic insufficiency at screening.
• Has both moderate hepatic insufficiency AND moderate-to-severe renal insufficiency at screening.
• Has any uncontrolled infection on the day of randomization.
• Has documented positive results for human immunodeficiency virus antibody (HIV-Ab) test at any time prior to randomization, or for hepatitis C virus antibody (HCV-Ab) and with detectable HCV ribonucleic acid (RNA) within 90 days prior to randomization, or hepatitis B surface antigen (HBsAg) within 90 days prior to randomization.
• Requires mechanical ventilation, or is hemodynamically unstable, at the time of randomization.
• Has a history of malignancy ≤5 years prior to signing informed consent.
• Is pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from the time of consent through at least 90 days following cessation of study therapy.
• Is expecting to donate eggs or sperm starting from the time of consent through at least 90 days following cessation of study therapy.
• Has received within 30 days prior to randomization or plans to receive during the study any of the following anti-CMV IgG antibody treatment or anti-CMV drug therapy including the following: Cidofovir, CMV hyper-immune globulin, Any investigational CMV antiviral agent/biologic therapy.
• Has received within 7 days prior to randomization or plans to receive during the study any of the following anti-CMV drug therapy: LET, GCV, VGCV, Foscarnet, ACV, Valacyclovir, Famciclovir.
• Is a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence.
• Is currently participating or has participated in a study with an unapproved investigational compound or device within 28 days, or 5× half-life of the investigational compound whichever is longer, of initial dosing on 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.