Clinically significant CMV infection
Conditions
Interventions
Product Name: Letermovir
Product Code: MK-8228
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: letermovir
CAS Number: 917389-32-3
Current Sponsor code: MK-8228
Concentration unit: mg mill
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
Eligibility
Sex/Gender
All
Inclusion criteria
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
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 (if tested) at any time from either signing of the ICF or the HSCT procedure, whichever is earlier, until the time of randomization. (Note: Evidence of CMV viremia as reported by central lab will include reporting of test results as “detectable, not quantifiable” or “detected” with a numeric value provided.) 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 severe hepatic insufficiency within 5 days prior to randomization. 7. 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 within 5 days prior to randomization. 8. has end-stage renal impairment with a creatinine clearance less than 10 mL/min, as calculated by the Cockcroft-Gault equation using serum creatinine within 5 days prior to randomization. 9. has an uncontrolled infection on the day of randomization. 10. requires mechanical ventilation or is hemodynamically unstable at the time of randomization. 11. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of MK-8228 in the prevention of clinically significant CMV infection through Week 24 (~6 months) post-transplant following administration of MK-8228 or placebo.;Secondary Objective: 1) To evaluate the safety and tolerability of MK-8228. 2) To evaluate the efficacy of MK-8228 in the prevention of clinically significant CMV infection through Week 14 (~100 days) post-transplant. 3) To evaluate the efficacy of MK-8228 as assessed by time to onset of clinically significant CMV infection through Week 24 (~6 months) post-transplant. 4) To determine the incidence of CMV disease through Week 14 post -transplant and Week 24 post-transplant. 5) To assess the incidence of PET for CMV viremia through Week 14 post-transplant and Week 24 post-transplant. 6) To assess the time to initiation of PET for CMV viremia through Week 14 post-transplant and Week 24 post-transplant. ;Primary end point(s): The primary efficacy endpoint of the study is the proportion of subjects with clinically significant CMV infection through Week 24 (~6 months) post-transplant, defined as the occurrence of either one of the following outcomes: •onset of CMV end-organ disease OR •initiation of anti-CMV PET based on documented CMV viremia (as measured by the central laboratory) and the clinical condition of the subject. Initiation of PET in this study refers to the practice of initiating therapy with the following approved anti-CMV agents when active CMV viral replication is documented: ganciclovir, valganciclovir, foscarnet, and/or cidofovir. ;Timepoint(s) of evaluation of this end point: Week 24 (~6 months) post- HSCT transplant | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Proportion of subjects with clinically significant CMV infection through Week 14 (~100 days) post-transplant 2. Time to onset of clinically significant CMV infection through Week 24 (~6 months) post-transplant 3. Proportion of subjects with CMV disease through Week 14 post-transplant and Week 24 post-transplant 4. Proportion of subjects with initiation of PET for documented CMV viremia through Week 14 post-transplant and Week 24 post-transplant. 5. The time to initiation of PET for documented CMV viremia through Week 24 post-transplant. ;Timepoint(s) of evaluation of this end point: Week 14, Week 24 | — |
Countries
Australia, Austria, Belgium, Brazil, Canada, Finland, France, Germany, Italy, Japan, Korea, Republic of, Lithuania, New Zealand, Peru, Poland, Romania, Spain, Sweden, Turkey, United Kingdom, United States
Contacts
Public ContactCyrus Badshah
Merck Sharp & Dohme Corp., a subsidiary of Merck
Outcome results
None listed