Letermovir (MK-8228) Versus Placebo in the Prevention of Clinically-Significant Cytomegalovirus (CMV) Infection in Adult, CMV-Seropositive Allogeneic Hematopoietic Stem Cell Transplant Recipients (MK-8228-001)
Condition: Prevention of CMV Infection or Disease
MeSH terms: Infections; Communicable Diseases; Cytomegalovirus Infections
Intervention: Letermovir; Placebo
Intervention description: Letermovir 240 mg / 480 mg tablets, or 240 mg / 480 mg intravenous solution in 250 mL to be infused over 60 minutes.; Placebo tablets, or intravenous solution in 250 mL to be infused over 60 minutes.
Intervention MeSH terms: Letermovir
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 570.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The study evaluated the efficacy and safety of letermovir (MK-8228) for the prevention of
      clinically-significant CMV infection in adult, CMV-seropositive recipients of allogeneic
      hematopoietic stem cell transplant (HSCT). The hypothesis being tested was that MK-8228 is
      superior to placebo in the prevention of clinically-significant CMV infection through Week 24
      post-transplant.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has documented seropositivity for CMV within 1 year before hematopoietic stem cell
             transplant (HSCT)

          -  Receiving first allogeneic HSCT (bone marrow, peripheral blood stem cell, or cord
             blood transplant)

          -  Female or male participant who is not of reproductive potential, or, if of
             reproductive potential, agrees to true abstinence or to use (or have their partner
             use) 2 acceptable methods of birth control from the time of consent through 90 days
             after the last dose of study drug

          -  Able to read, understand, and complete questionnaires and diaries

        Exclusion Criteria:

          -  Received a previous allogeneic HSCT (previous autologous HSCT is acceptable)

          -  History of CMV end-organ disease within 6 months before randomization

          -  Has evidence of CMV viremia (if tested) at any time from either signing of the
             Informed Consent Form or the HSCT procedure, whichever is earlier, until the time of
             randomization.

          -  Received the following within 7 days before screening or plans to receive during the
             study: ganciclovir, valganciclovir, foscarnet, acyclovir, valacyclovir, or famciclovir

          -  Received the following within 30 days before screening or plan to receive during the
             study: cidofovir, CMV hyper-immune globulin, any investigational CMV antiviral agent
             or biological therapy

          -  Has suspected or known hypersensitivity to ingredients of MK-8228 (letermovir)
             formulations

          -  Has severe hepatic insufficiency within 5 days before randomization

          -  Has end-stage renal impairment

          -  Has an uncontrolled infection on the day of randomization

          -  Requires mechanical ventilation or is hemodynamically unstable at the time of
             randomization

          -  Has documented positive results for human immunodeficiency virus (HIV) antibody,
             hepatitis C virus (HCV) antibody with detectable HCV ribonucleic acid, or hepatitis B
             surface antigen (HBsAg) within 90 days before randomization

          -  Has active solid tumor malignancies with the exception of localized basal cell or
             squamous cell skin cancer or the condition under treatment (for example, lymphoma)

          -  Is pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from
             the time of consent through 90 days after the last dose of study drug

          -  Is expecting to donate eggs or sperm from the time of consent through 90 days after
             the last dose of study drug

          -  Has participated in a study with an unapproved investigational compound (monoclonal
             antibodies are excepted) or device within 28 days of the first dose of study drug

          -  Has previously participated in a MK-8228 (letermovir) study

          -  Has, is, or is planning (during the study) to participate in any study involving
             administration of a CMV vaccine or another CMV investigational agent

          -  Is a user of recreational or illicit drugs or has a recent history (<=1 year) of drug
             or alcohol abuse or dependence