Clinical trial NCT03443869: Letermovir Versus Valganciclovir to Prevent Human Cytomegalovirus Disease in Kidney Transplant Recipients (MK-8228-002)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: CMV Disease
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2018-02-23
Enrollment: 601
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* Has received a previous solid organ transplant or hematopoietic stem cell transplant (HSCT). Note: Participants who have received a prior primary allograft kidney may be enrolled, provided that all other inclusion/exclusion criteria are met.
* 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.

Primary outcomes:
measure: Percentage of Participants With Adjudicated Cytomegalovirus (CMV) Disease Through 52 Weeks Post-transplant
timeFrame: Up to 52 weeks
Secondary outcomes:
measure: Percentage of Participants With Adjudicated CMV Disease Through 28 Weeks Post-transplant
timeFrame: Up to 28 weeks
measure: Time to Onset of Adjudicated CMV Disease Through 52 Weeks Post-transplant
timeFrame: Up to 52 weeks
measure: Percentage of Participants With Any AE
timeFrame: Up to 52 weeks
measure: Percentage of Participants With Any Drug-related Serious Adverse Event (SAE)
timeFrame: Up to 52 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB ( Site 0269)
state: Alabama
city: Los Angeles
country: United States
facility: UCLA Medical Center ( Site 0266)
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center ( Site 0271)
state: California
city: San Francisco
country: United States
facility: University of California-San Francisco ( Site 0236)
state: California
city: Stanford
country: United States
facility: Stanford Health Care ( Site 0235)
state: California
city: Atlanta
country: United States
facility: The Emory Clinic ( Site 0247)
state: Georgia
city: Chicago
country: United States
facility: University of Chicago ( Site 0251)
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University ( Site 0261)
state: Indiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation ( Site 0238)
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center ( Site 0234)
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital ( Site 0232)
state: Maryland
city: Boston
country: United States
facility: Brigham & Women's Hospital ( Site 0244)
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital ( Site 0242)
state: Michigan
city: Omaha
country: United States
facility: University of Nebraska Medical Center ( Site 0272)
state: Nebraska
city: Livingston
country: United States
facility: Saint Barnabas Medical Center ( Site 0250)
state: New Jersey
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai ( Site 0256)
state: New York
city: New York
country: United States
facility: Columbia University Medical Center ( Site 0255)
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital - Weill Cornell Medical Center ( Site 0276)
state: New York
city: Durham
country: United States
facility: Duke University Medical Center ( Site 0243)
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center ( Site 0260)
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center ( Site 0264)
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania ( Site 0270)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh ( Site 0252)
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina ( Site 0257)
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center ( Site 0275)
state: Tennessee
city: Richmond
country: United States
facility: Virginia Commonwealth University ( Site 0245)
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center ( Site 0246)
state: Washington
city: Florencio Varela
country: Argentina
facility: Hospital El Cruce Nestor Carlos Kirchner ( Site 0351)
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: CEMIC ( Site 0352)
state: Caba
city: Buenos Aires
country: Argentina
facility: Instituto de Nefrologia Nephrology S.A. ( Site 0182)
city: Caba
country: Argentina
facility: Hospital Italiano de Buenos Aires ( Site 0188)
city: Corrientes
country: Argentina
facility: Instituto de Cardiología de Corrientes Juana F. Cabral ( Site 0181)
city: Santa Fe
country: Argentina
facility: Clinica de nefrologia urologia y enfermedades cardiovasculares ( Site 0354)
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital ( Site 0005)
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital ( Site 0006)
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital ( Site 0004)
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital ( Site 0003)
state: South Australia
city: Clayton
country: Australia
facility: Monash Health-Monash Medical Centre ( Site 0008)
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital ( Site 0007)
state: Victoria
city: Innsbruck
country: Austria
facility: Medizinische Universitat Innsbruck ( Site 0033)
state: Tirol
city: Wien
country: Austria
facility: Allgemeines Krankenhaus Universitaetskliniken Wien ( Site 0032)
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen ( Site 0041)
state: Antwerpen
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires de Bruxelles - CUB - Hopital Erasme ( Site 0042)
state: Bruxelles-Capitale, Region De
city: Leuven
country: Belgium
facility: UZ Leuven - Campus Gasthuisberg ( Site 0044)
state: Vlaams-Brabant
city: Edmonton
country: Canada
facility: University of Alberta Hospital ( Site 0221)
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital ( Site 0224)
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital ( Site 0225)
state: British Columbia
city: Toronto
country: Canada
facility: Toronto General Hospital ( Site 0222)
state: Ontario
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont CIUSSS de l Est de L Ile de Montreal ( Site 0226)
state: Quebec
city: Rionegro
country: Colombia
facility: Hospital San Vicente Fundación - Rionegro ( Site 0205)
state: Antioquia
city: Bogota
country: Colombia
facility: Clinica del Country ( Site 0208)
state: Distrito Capital De Bogota
city: Bogota
country: Colombia
facility: Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 0209)
state: Distrito Capital De Bogota
city: Bogota
country: Colombia
facility: Hospital Universitario Mayor Mederi CIMED ( Site 0206)
state: Distrito Capital De Bogota
city: Bogota
country: Colombia
facility: Sociedad de Cirugia de Bogota Hospital de San Jose ( Site 0203)
state: Distrito Capital De Bogota
city: Bucaramanca
country: Colombia
facility: Fundacion Cardiovascular de Colombia ( Site 0210)
state: Santander
city: Cali
country: Colombia
facility: Fundacion Valle del Lili ( Site 0285)
state: Valle Del Cauca
city: Cali
country: Colombia
facility: Centro Medico Imbanaco de Cali S.A ( Site 0201)
state: Valle Del Cauca
city: Nice
country: France
facility: Hopital Pasteur ( Site 0053)
state: Alpes-Maritimes
city: Bordeaux
country: France
facility: CHU de Bordeaux. Hopital Pellegrin ( Site 0055)
state: Gironde
city: Toulouse
country: France
facility: CHU Rangueil ( Site 0054)
state: Haute-Garonne
city: Tours
country: France
facility: C.H.R.U Bretonneau ( Site 0051)
state: Indre-et-Loire
city: Creteil
country: France
facility: Hopital Henri Mondor du Creteil ( Site 0063)
state: Val-de-Marne
city: Le kremlin bicetre
country: France
facility: CHU - Hopital de Bicetre ( Site 0060)
state: Val-de-Marne
city: Paris
country: France
facility: Hopital Tenon ( Site 0061)
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover ( Site 0073)
state: Niedersachsen
city: Essen
country: Germany
facility: Universitaetsklinikum Essen ( Site 0074)
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin ( Site 0071)
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem AOK ( Site 0282)
state: Baranya
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem ( Site 0284)
state: Csongrad
city: Budapest
country: Hungary
facility: Semmelweis Egyetem ( Site 0281)
city: Debrecen
country: Hungary
facility: Debreceni Egyetem. ( Site 0283)
city: Torino
country: Italy
facility: A.O.U. Citta della Salute e della Scienza di Torino ( Site 0096)
state: Piemonte
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova U.O.C. Trapianti Rene e Pancreas ( Site 0091)
state: Veneto
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele di Milano ( Site 0098)
city: Roma
country: Italy
facility: Policlinico Gemelli Instituto di Clinica Chirurgica ( Site 0093)
city: Cuernavaca
country: Mexico
facility: Instituto Mexicano de Trasplantes S C ( Site 0212)
state: Morelos
city: Aguascalientes
country: Mexico
facility: Centenario Hospital Miguel Hidalgo ( Site 0215)
city: Ciudad de Mexico
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0214)
city: Mexico City
country: Mexico
facility: Instituto Nacional de Cardiologia Ignacio Chavez ( Site 0213)
city: Veracruz
country: Mexico
facility: Faicic S de RL de CV ( Site 0211)
city: Auckland
country: New Zealand
facility: Auckland City Hospital ( Site 0002)
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego ( Site 0162)
state: Dolnoslaskie
city: Warszawa
country: Poland
facility: Szpital Kliniczny Dzieciatka Jezus ( Site 0165)
state: Mazowieckie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne ( Site 0170)
state: Pomorskie
city: Poznan
country: Poland
facility: Szpital Wojewodzki w Poznaniu ( Site 0168)
state: Wielkopolskie
city: Szczecin
country: Poland
facility: Pomorski Uniwersytet Medyczny ( Site 0167)
state: Zachodniopomorskie
city: Barcelona
country: Spain
facility: Hospital del Mar ( Site 0121)
state: La Coruna
city: L Hospitalet De Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge IDIBELL ( Site 0114)
state: La Coruna
city: Barcelona
country: Spain
facility: Hospital Universitari Vall de Hebron ( Site 0112)
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona ( Site 0113)
city: Madrid
country: Spain
facility: Hospital Doce de Octubre ( Site 0116)
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet ( Site 0118)
city: London
country: United Kingdom
facility: St Georges University Hospitals NHS Foundation Trust. ( Site 0136)
state: London, City Of
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital ( Site 0356)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Limaye AP, Budde K, Humar A, Vincenti F, Kuypers DRJ, Carroll RP, Stauffer N, Murata Y, Strizki JM, Teal VL, Gilbert CL, Haber BA. Letermovir vs Valganciclovir for Prophylaxis of Cytomegalovirus in High-Risk Kidney Transplant Recipients: A Randomized Clinical Trial. JAMA. 2023 Jul 3;330(1):33-42. doi: 10.1001/jama.2023.9106.