Letermovir Versus Valganciclovir to Prevent Human Cytomegalovirus Disease in Kidney Transplant Recipients (MK-8228-002)

NCT ID: NCT03443869

Last Updated: 2023-07-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

601 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-03

Study Completion Date

2022-04-05

Brief Summary

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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.

Detailed Description

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Conditions

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CMV Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Letermovir

LET 480mg (or 240 mg when administered concomitantly with cyclosporin A) tablet orally; placebo to VGCV tablet orally once daily; and 400 mg capsule of acyclovir (ACV) orally every 12 hours for 28 weeks

Group Type EXPERIMENTAL

Letermovir

Intervention Type DRUG

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

Acyclovir (ACV)

Intervention Type DRUG

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

Placebo to VGCV

Intervention Type DRUG

Placebo to VGCV tablet orally, once daily for 28 weeks

Valganciclovir

900 mg VGCV tablet orally, once daily; placebo to LET tablet orally once daily; and placebo to ACV orally every 12 hours for 28 weeks

Group Type ACTIVE_COMPARATOR

Valganciclovir

Intervention Type DRUG

900 mg VGCV tablet orally, once daily for 28 weeks

Placebo to ACV

Intervention Type DRUG

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

Placebo to LET

Intervention Type DRUG

Placebo to LET tablet orally, once daily for 28 weeks

Interventions

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Letermovir

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

Intervention Type DRUG

Valganciclovir

900 mg VGCV tablet orally, once daily for 28 weeks

Intervention Type DRUG

Acyclovir (ACV)

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

Intervention Type DRUG

Placebo to ACV

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

Intervention Type DRUG

Placebo to LET

Placebo to LET tablet orally, once daily for 28 weeks

Intervention Type DRUG

Placebo to VGCV

Placebo to VGCV tablet orally, once daily for 28 weeks

Intervention Type DRUG

Eligibility Criteria

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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

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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UAB ( Site 0269)

Birmingham, Alabama, United States

Site Status

UCLA Medical Center ( Site 0266)

Los Angeles, California, United States

Site Status

UC Davis Medical Center ( Site 0271)

Sacramento, California, United States

Site Status

University of California-San Francisco ( Site 0236)

San Francisco, California, United States

Site Status

Stanford Health Care ( Site 0235)

Stanford, California, United States

Site Status

The Emory Clinic ( Site 0247)

Atlanta, Georgia, United States

Site Status

University of Chicago ( Site 0251)

Chicago, Illinois, United States

Site Status

Indiana University ( Site 0261)

Indianapolis, Indiana, United States

Site Status

Ochsner Clinic Foundation ( Site 0238)

New Orleans, Louisiana, United States

Site Status

University of Maryland Medical Center ( Site 0234)

Baltimore, Maryland, United States

Site Status

Johns Hopkins Hospital ( Site 0232)

Baltimore, Maryland, United States

Site Status

Brigham & Women's Hospital ( Site 0244)

Boston, Massachusetts, United States

Site Status

Henry Ford Hospital ( Site 0242)

Detroit, Michigan, United States

Site Status

University of Nebraska Medical Center ( Site 0272)

Omaha, Nebraska, United States

Site Status

Saint Barnabas Medical Center ( Site 0250)

Livingston, New Jersey, United States

Site Status

Icahn School of Medicine at Mount Sinai ( Site 0256)

New York, New York, United States

Site Status

Columbia University Medical Center ( Site 0255)

New York, New York, United States

Site Status

New York Presbyterian Hospital - Weill Cornell Medical Center ( Site 0276)

New York, New York, United States

Site Status

Duke University Medical Center ( Site 0243)

Durham, North Carolina, United States

Site Status

Wake Forest University Baptist Medical Center ( Site 0260)

Winston-Salem, North Carolina, United States

Site Status

The Ohio State University Wexner Medical Center ( Site 0264)

Columbus, Ohio, United States

Site Status

University of Pennsylvania ( Site 0270)

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh ( Site 0252)

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina ( Site 0257)

Charleston, South Carolina, United States

Site Status

Vanderbilt University Medical Center ( Site 0275)

Nashville, Tennessee, United States

Site Status

Virginia Commonwealth University ( Site 0245)

Richmond, Virginia, United States

Site Status

University of Washington Medical Center ( Site 0246)

Seattle, Washington, United States

Site Status

Hospital El Cruce Nestor Carlos Kirchner ( Site 0351)

San Juan Bautista, Buenos Aires, Argentina

Site Status

CEMIC ( Site 0352)

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

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

Buenos Aires, , Argentina

Site Status

Hospital Italiano de Buenos Aires ( Site 0188)

CABA, , Argentina

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

Corrientes, , Argentina

Site Status

Clinica de nefrologia urologia y enfermedades cardiovasculares ( Site 0354)

Santa Fe, , Argentina

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Royal Prince Alfred Hospital ( Site 0005)

Camperdown, New South Wales, Australia

Site Status

Westmead Hospital ( Site 0006)

Westmead, New South Wales, Australia

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Princess Alexandra Hospital ( Site 0004)

Woolloongabba, Queensland, Australia

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Royal Adelaide Hospital ( Site 0003)

Adelaide, South Australia, Australia

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Monash Health-Monash Medical Centre ( Site 0008)

Clayton, Victoria, Australia

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Royal Melbourne Hospital ( Site 0007)

Parkville, Victoria, Australia

Site Status

Medizinische Universitat Innsbruck ( Site 0033)

Innsbruck, Tyrol, Austria

Site Status

Allgemeines Krankenhaus Universitaetskliniken Wien ( Site 0032)

Vienna, , Austria

Site Status

Universitair Ziekenhuis Antwerpen ( Site 0041)

Edegem, Antwerpen, Belgium

Site Status

Cliniques Universitaires de Bruxelles - CUB - Hopital Erasme ( Site 0042)

Brussels, Bruxelles-Capitale, Region de, Belgium

Site Status

UZ Leuven - Campus Gasthuisberg ( Site 0044)

Leuven, Vlaams-Brabant, Belgium

Site Status

University of Alberta Hospital ( Site 0221)

Edmonton, Alberta, Canada

Site Status

Vancouver General Hospital ( Site 0224)

Vancouver, British Columbia, Canada

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St. Paul's Hospital ( Site 0225)

Vancouver, British Columbia, Canada

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Toronto General Hospital ( Site 0222)

Toronto, Ontario, Canada

Site Status

Hopital Maisonneuve-Rosemont CIUSSS de l Est de L Ile de Montreal ( Site 0226)

Montreal, Quebec, Canada

Site Status

Hospital San Vicente Fundación - Rionegro ( Site 0205)

Rionegro, Antioquia, Colombia

Site Status

Clinica del Country ( Site 0208)

Bogotá, Bogota D.C., Colombia

Site Status

Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 0209)

Bogotá, Bogota D.C., Colombia

Site Status

Hospital Universitario Mayor Mederi CIMED ( Site 0206)

Bogotá, Bogota D.C., Colombia

Site Status

Sociedad de Cirugia de Bogota Hospital de San Jose ( Site 0203)

Bogotá, Bogota D.C., Colombia

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Fundacion Cardiovascular de Colombia ( Site 0210)

Bucaramanca, Santander Department, Colombia

Site Status

Fundacion Valle del Lili ( Site 0285)

Cali, Valle del Cauca Department, Colombia

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Centro Medico Imbanaco de Cali S.A ( Site 0201)

Cali, Valle del Cauca Department, Colombia

Site Status

Hopital Pasteur ( Site 0053)

Nice, Alpes-Maritimes, France

Site Status

CHU de Bordeaux. Hopital Pellegrin ( Site 0055)

Bordeaux, Gironde, France

Site Status

CHU Rangueil ( Site 0054)

Toulouse, Haute-Garonne, France

Site Status

C.H.R.U Bretonneau ( Site 0051)

Tours, Indre-et-Loire, France

Site Status

Hopital Henri Mondor du Creteil ( Site 0063)

Créteil, Val-de-Marne, France

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CHU - Hopital de Bicetre ( Site 0060)

Le Kremlin-Bicêtre, Val-de-Marne, France

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Hopital Tenon ( Site 0061)

Paris, , France

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Medizinische Hochschule Hannover ( Site 0073)

Hanover, Lower Saxony, Germany

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Universitaetsklinikum Essen ( Site 0074)

Essen, North Rhine-Westphalia, Germany

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Charite Universitaetsmedizin Berlin ( Site 0071)

Berlin, , Germany

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Pecsi Tudomanyegyetem AOK ( Site 0282)

Pécs, Baranya, Hungary

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Szegedi Tudomanyegyetem ( Site 0284)

Szeged, Csongrád megye, Hungary

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Semmelweis Egyetem ( Site 0281)

Budapest, , Hungary

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Debreceni Egyetem. ( Site 0283)

Debrecen, , Hungary

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A.O.U. Citta della Salute e della Scienza di Torino ( Site 0096)

Turin, Piedmont, Italy

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Azienda Ospedaliera di Padova U.O.C. Trapianti Rene e Pancreas ( Site 0091)

Padua, Veneto, Italy

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IRCCS Ospedale San Raffaele di Milano ( Site 0098)

Milan, , Italy

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Policlinico Gemelli Instituto di Clinica Chirurgica ( Site 0093)

Roma, , Italy

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Instituto Mexicano de Trasplantes S C ( Site 0212)

Cuernavaca, Morelos, Mexico

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Centenario Hospital Miguel Hidalgo ( Site 0215)

Aguascalientes, , Mexico

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Instituto Nacional de Cardiologia Ignacio Chavez ( Site 0213)

Mexico City, , Mexico

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Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0214)

Mexico City, , Mexico

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Faicic S de RL de CV ( Site 0211)

Veracruz, , Mexico

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Auckland City Hospital ( Site 0002)

Auckland, , New Zealand

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Szpital Wojewodzki w Poznaniu ( Site 0168)

Poznan, Greater Poland Voivodeship, Poland

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Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego ( Site 0162)

Wroclaw, Lower Silesian Voivodeship, Poland

Site Status

Szpital Kliniczny Dzieciatka Jezus ( Site 0165)

Warsaw, Masovian Voivodeship, Poland

Site Status

Uniwersyteckie Centrum Kliniczne ( Site 0170)

Gdansk, Pomeranian Voivodeship, Poland

Site Status

Pomorski Uniwersytet Medyczny ( Site 0167)

Szczecin, West Pomeranian Voivodeship, Poland

Site Status

Hospital del Mar ( Site 0121)

Barcelona, La Coruna, Spain

Site Status

Hospital Universitari de Bellvitge IDIBELL ( Site 0114)

L'Hospitalet de Llobregat, La Coruna, Spain

Site Status

Hospital Universitari Vall de Hebron ( Site 0112)

Barcelona, , Spain

Site Status

Hospital Clinic i Provincial de Barcelona ( Site 0113)

Barcelona, , Spain

Site Status

Hospital Doce de Octubre ( Site 0116)

Madrid, , Spain

Site Status

Hospital Universitario Miguel Servet ( Site 0118)

Zaragoza, , Spain

Site Status

St Georges University Hospitals NHS Foundation Trust. ( Site 0136)

London, London, City of, United Kingdom

Site Status

Queen Elizabeth Hospital ( Site 0356)

Birmingham, , United Kingdom

Site Status

Countries

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United States Argentina Australia Austria Belgium Canada Colombia France Germany Hungary Italy Mexico New Zealand Poland Spain United Kingdom

References

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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.

Reference Type RESULT
PMID: 37279999 (View on PubMed)

Strizki JM, Diamond TL, Teal VL, Gilbert CL, Wang W, Stauffer N, Haber BA. Cytomegalovirus Antiviral Resistance Among Kidney Transplant Recipients in a Phase 3 Trial of Letermovir vs Valganciclovir Prophylaxis. J Infect Dis. 2024 Dec 16;230(6):e1287-e1298. doi: 10.1093/infdis/jiae287.

Reference Type DERIVED
PMID: 38853607 (View on PubMed)

Vernooij RW, Michael M, Ladhani M, Webster AC, Strippoli GF, Craig JC, Hodson EM. Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2024 May 3;5(5):CD003774. doi: 10.1002/14651858.CD003774.pub5.

Reference Type DERIVED
PMID: 38700045 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://merckclinicaltrials.com

Merck Clinical Trial Information

Other Identifiers

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MK-8228-002

Identifier Type: OTHER

Identifier Source: secondary_id

2017-001055-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8228-002

Identifier Type: -

Identifier Source: org_study_id

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