Resumen

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.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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.

Criterios de exclusión

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.

Intervenciones

drug

Letermovir

LET 480mg (or 240 mg when administered concomitantly with cyclosporin A) once daily for 28 weeks

drug

Valganciclovir

900 mg VGCV tablet orally, once daily for 28 weeks

drug

Acyclovir (ACV)

400 mg over-encapsulated ACV tablet orally, every 12 hours for 28 weeks

drug

Placebo to ACV

Over-encapsulated placebo tablet orally, every 12 hours for 28 weeks

drug

Placebo to LET

Placebo to LET tablet orally, once daily for 28 weeks

drug

Placebo to VGCV

Placebo to VGCV tablet orally, once daily for 28 weeks

Ubicaciones

Hospital El Cruce Nestor Carlos Kirchner ( Site 0351)

San Juan Bautista, Buenos Aires, Argentina

CEMIC ( Site 0352)

Buenos Aires, Buenos Aires F.D., Argentina

Instituto de Nefrologia Nephrology S.A. ( Site 0182)

Buenos Aires, Argentina

Hospital Italiano de Buenos Aires ( Site 0188)

CABA, Argentina

Instituto de Cardiología de Corrientes Juana F. Cabral ( Site 0181)

Corrientes, Argentina

Clinica de nefrologia urologia y enfermedades cardiovasculares ( Site 0354)

Santa Fe, Argentina

A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Study to Evaluate the Efficacy and Safety of MK-8228 (Letermovir) Versus Valganciclovir for the Prevention of Human Cytomegalovirus (CMV) Disease in Adult Kidney Transplant Recipients

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Letermovir

Valganciclovir

Acyclovir (ACV)

Placebo to ACV

Placebo to LET

Placebo to VGCV

Ubicaciones

Hospital El Cruce Nestor Carlos Kirchner ( Site 0351)

CEMIC ( Site 0352)

Instituto de Nefrologia Nephrology S.A. ( Site 0182)

Hospital Italiano de Buenos Aires ( Site 0188)

Instituto de Cardiología de Corrientes Juana F. Cabral ( Site 0181)

Clinica de nefrologia urologia y enfermedades cardiovasculares ( Site 0354)

Patrocinadores