MK-8228 vs. Placebo in Prevention of CMV infection in HSCT Recipients

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 540

Inclusion Criteria

1. be = 18 years of age on the day of signing informed consent.
2. have documented seropositivity for CMV (recipient CMV IgG seropositivity [R+]) within 1 year before HSCT.
3. be receiving a first allogeneic HSCT (bone marrow, peripheral blood stem cell, or cord blood transplant).
4. have undetectable CMV DNA (as confirmed by the central laboratory) from a plasma sample collected within 5 days prior to randomization.
5. be within 28 days post-HSCT at the time of randomization.
6. be highly unlikely to become pregnant or to impregnate a partner

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 270
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 270

Exclusion Criteria

1. received a previous allogeneic HSCT
2. has a history of CMV end-organ disease within 6 months prior to randomization.
3. has evidence of CMV viremia from a central or local laboratory at any time prior to randomization.
4. received within 7 days prior to screening or plans to receive during the study any of the following: ganciclovir; valganciclovir; foscarnet; acyclovir (at doses > 3200 mg PO per day or > 25 mg/kg IV per day); valacyclovir (at doses > 3000 mg PO per day); famciclovir (at doses > 1500 mg PO per day)
5. received within 30 days prior to screening or plans to receive during the study any of the following: cidofovir; CMV hyper-immune globulin; Any investigational CMV antiviral agent/biologic therapy
6. has suspected or known hypersensitivity to active or inactive ingredients of
letermovir formulations.
7. has severe hepatic insufficiency (defined as Child-Pugh Class C; see Appendix 12.5).
8. has serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 x the upper limit of normal (ULN) or serum total bilirubin > 2.5 x ULN.
9. has end-stage renal impairment with a creatinine clearance less than 10 mL/min, as calculated by the Cockcroft-Gault equation using serum creatinine.
10. has both moderate hepatic insufficiency AND moderate renal insufficiency.
11. has an uncontrolled infection on the day of randomization.
12. requires mechanical ventilation or is hemodynamically unstable at the time of rndomization.
13. has documented positive results for human immunodeficiency virus antibody (HIVAb), hepatitis C virus antibody (HCV-Ab) with detectable HCV RNA, or hepatitis B
surface antigen (HBsAg) within 90 days prior to randomization.
14. 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).
15. 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 therapy.
16. is expecting to donate eggs or sperm starting from the time of consent through 90 days after the last dose of study therapy.
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 on this study. Subjects previously treated with a monoclonal antibody
will be eligible to participate after a 28-day washout period.
18. has previously participated in this study or any other study involving MK-8228
(letermovir).
19. 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.
20. is or has an immediate family member (spouse or children) who is investigational site or Sponsor staff directly involved with this trial.
21. is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence.
22. has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or would be put at undue risk as j