Prevention of CMV disease in D+/R- kidney transplant recipients MedDRA version: 20.1 Level: PT Classification code 10011831 Term: Cytomegalovirus infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: LETERMOVIR
Product Code: MK-8228
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: LETERMOVIR
CAS Number: 91738
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have a documented negative serostatus for CMV (ie, recipient CMV IgG seronegative [R-]) within 90 days prior to randomization. 2. Anticipate receiving a first allograft kidney from a CMV IgG seropositive (D+) donor at the time of screening AND have received a first allograft kidney from a documented D+ donor at the time of randomization. 3. Be within 0 (ie, day of transplantation) to 7 days (inclusive) post-kidney transplant at the time of randomization. 4. Be =18 years of age on day of signing informed consent. 5. A male participant must agree to use contraception as detailed in Appendix 5 of the protocol 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. 6. A female participant is eligible to participate if she is not pregnant (see Appendix 5), not breastfeeding, and at least one of the following conditions applies: a. Not a woman of childbearing potential (WOCBP), as defined in Appendix 5 OR b. A WOCBP who agrees to follow the contraception guidance in Appendix 5 during the treatment period and for at least 90 days after the last dose of study treatment. 7. Understand the study procedures, alternative treatment available, and risks involved with the study, and he/she voluntarily agrees to participate by giving written informed consent and is willing to adhere to dose and visit schedules. Participant may also provide consent for Future Biomedical Research. However, the participant may participate in the main study without participating in Future Biomedical Research. 8. Be able to read, understand, and complete questionnaires and diaries. 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 510 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 90
Exclusion criteria
Exclusion criteria: 1. Received a previous solid organ transplant or HSCT. 2. Is a multi-organ transplant recipient (eg, kidney-pancreas). 3. Has a history of CMV disease or suspected CMV disease within 6 months prior to randomization. 4. Has suspected or known hypersensitivity to active or inactive ingredients of LET formulations, VGCV, GCV, and/or ACV formulations. 5. Is on dialysis at the time of randomization. 6. Has post-transplant renal function of CrCl =10 mL/min at randomization (measured locally). For this exclusion criterion, CrCl will be calculated using the Cockcroft-Gault equation using the most recently obtained and available serum creatinine value collected within 3 calendar days prior to and including the day of randomization and after the conclusion of any clinically warranted (at the discretion of the investigator) post-transplant dialysis. 7. Has Child-Pugh Class C severe hepatic insufficiency (Appendix 8 of the protocol) at screening. 8. Has both moderate hepatic insufficiency AND moderate-to-severe renal insufficiency at screening. 9. Has any uncontrolled infection on the day of randomization. 10. 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) or hepatitis B surface antigen (HBsAg) within 90 days prior to randomization. 11. Requires mechanical ventilation, or is hemodynamically unstable, at the time of randomization. 12. Has a history of malignancy =5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or is under evaluation for other active or suspected malignancy. 13. 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. 14. Is expecting to donate eggs or sperm starting from the time of consent through at least 90 days following cessation of study therapy. 15. 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 participant’s participation for the full duration of the study, or put the participant at undue risk, as judged by the investigator, such that it is not in the best interest of the participant to participate in this study. 16. Has exclusionary laboratory value at the screening visit, as listed in the protocol. 17. 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: a. Cidofovir b. CMV hyper-immune globulin c. Any investigational CMV antiviral agent/biologic therapy. 18. Has received within 7 days prior to randomization or plans to receive during the study any of the following anti-CMV drug therapy including: a. LET b. GCV c. VGCV d. Foscarnet e. ACV (at doses > 3200 mg PO per day or > 25 mg/kg IV per day)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of letermovir (LET) versus valganciclovir (VGCV), as measured by the proportion of participants with adjudicated CMV disease through 52 weeks post-transplant.; Secondary Objective: 1. To evaluate the efficacy of LET versus VGCV, as measured by the proportion of participants with adjudicated CMV disease through 28 weeks post-transplant. 2. To evaluate the efficacy of LET versus VGCV, as measured by the time to onset of adjudicated CMV disease through 52 weeks post-transplant. 3. To evaluate the safety and tolerability of LET versus VGCV. ;Primary end point(s): Proportion of participants with adjudicated CMV disease through 52 weeks post-transplant;Timepoint(s) of evaluation of this end point: Proportion of participants with adjudicated CMV disease through 52 weeks post-transplant. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. 28 weeks post-transplant 2. 52 weeks post-transplant ; Timepoint(s) of evaluation of this end point: 1. Proportion of participants with adjudicated CMV disease through 28 weeks post transplant. 2. Time to onset of adjudicated CMV disease through 52 weeks post-transplant. | — |
Countries
Argentina, Australia, Austria, Belgium, Canada, Colombia, France, Germany, Hungary, Italy, Mexico, New Zealand, Poland, Spain, United Kingdom, United States
Contacts
Public ContactInvestigación Clínica
Merck Sharp & Dohme de España S.A.
Outcome results
None listed