Letermovir Versus Valganciclovir to Prevent Human Cytomegalovirus Disease in Kidney Transplant Recipients (MK-8228-002)
Condition: CMV Disease
Intervention: Letermovir; Valganciclovir; Acyclovir (ACV); Placebo to ACV; Placebo to LET; Placebo to VGCV
Intervention description: LET 480mg (or 240 mg when administered concomitantly with cyclosporin A) once daily for 28 weeks; 900 mg VGCV tablet orally, once daily for 28 weeks; 400 mg over-encapsulated ACV tablet orally, every 12 hours for 28 weeks; Over-encapsulated placebo tablet orally, every 12 hours for 28 weeks; Placebo to LET tablet orally, once daily for 28 weeks; Placebo to VGCV tablet orally, once daily for 28 weeks
Intervention MeSH terms: Acyclovir; Valganciclovir; Letermovir
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 601.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to evaluate the efficacy of letermovir (LET) versus
      valganciclovir (VGCV) in preventing CMV disease in adult kidney transplant recipients. The
      primary hypotheses are that LET is non-inferior to VGCV; and if non-inferiority is
      demonstrated, that LET is superior to VGCV, in preventing CMV disease through 52 weeks
      post-transplant.
    

Eligibility criteria:

        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.