CMV Disease Clinical Trial
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
| Verified date | July 2023 |
| Source | Merck Sharp & Dohme LLC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 601 |
| Est. completion date | April 5, 2022 |
| Est. primary completion date | April 5, 2022 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | CEMIC ( Site 0352) | Buenos Aires | Caba |
| 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 | Hospital El Cruce Nestor Carlos Kirchner ( Site 0351) | Florencio Varela | Buenos Aires |
| Argentina | Clinica de nefrologia urologia y enfermedades cardiovasculares ( Site 0354) | Santa Fe | |
| Australia | Royal Adelaide Hospital ( Site 0003) | Adelaide | South Australia |
| Australia | Royal Prince Alfred Hospital ( Site 0005) | Camperdown | New South Wales |
| Australia | Monash Health-Monash Medical Centre ( Site 0008) | Clayton | Victoria |
| Australia | Royal Melbourne Hospital ( Site 0007) | Parkville | Victoria |
| Australia | Westmead Hospital ( Site 0006) | Westmead | New South Wales |
| Australia | Princess Alexandra Hospital ( Site 0004) | Woolloongabba | Queensland |
| Austria | Medizinische Universitat Innsbruck ( Site 0033) | Innsbruck | Tirol |
| Austria | Allgemeines Krankenhaus Universitaetskliniken Wien ( Site 0032) | Wien | |
| Belgium | Cliniques Universitaires de Bruxelles - CUB - Hopital Erasme ( Site 0042) | Bruxelles | Bruxelles-Capitale, Region De |
| Belgium | Universitair Ziekenhuis Antwerpen ( Site 0041) | Edegem | Antwerpen |
| Belgium | UZ Leuven - Campus Gasthuisberg ( Site 0044) | Leuven | Vlaams-Brabant |
| Canada | University of Alberta Hospital ( Site 0221) | Edmonton | Alberta |
| Canada | Hopital Maisonneuve-Rosemont CIUSSS de l Est de L Ile de Montreal ( Site 0226) | Montreal | Quebec |
| Canada | Toronto General Hospital ( Site 0222) | Toronto | Ontario |
| Canada | St. Paul's Hospital ( Site 0225) | Vancouver | British Columbia |
| Canada | Vancouver General Hospital ( Site 0224) | Vancouver | British Columbia |
| Colombia | Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 0209) | Bogota | Distrito Capital De Bogota |
| Colombia | Clinica del Country ( Site 0208) | Bogota | Distrito Capital De Bogota |
| Colombia | Hospital Universitario Mayor Mederi CIMED ( Site 0206) | Bogota | Distrito Capital De Bogota |
| Colombia | Sociedad de Cirugia de Bogota Hospital de San Jose ( Site 0203) | Bogota | Distrito Capital De Bogota |
| Colombia | Fundacion Cardiovascular de Colombia ( Site 0210) | Bucaramanca | Santander |
| Colombia | Centro Medico Imbanaco de Cali S.A ( Site 0201) | Cali | Valle Del Cauca |
| Colombia | Fundacion Valle del Lili ( Site 0285) | Cali | Valle Del Cauca |
| Colombia | Hospital San Vicente Fundación - Rionegro ( Site 0205) | Rionegro | Antioquia |
| France | CHU de Bordeaux. Hopital Pellegrin ( Site 0055) | Bordeaux | Gironde |
| France | Hopital Henri Mondor du Creteil ( Site 0063) | Creteil | Val-de-Marne |
| France | CHU - Hopital de Bicetre ( Site 0060) | Le kremlin bicetre | Val-de-Marne |
| France | Hopital Pasteur ( Site 0053) | Nice | Alpes-Maritimes |
| France | Hopital Tenon ( Site 0061) | Paris | |
| France | CHU Rangueil ( Site 0054) | Toulouse | Haute-Garonne |
| France | C.H.R.U Bretonneau ( Site 0051) | Tours | Indre-et-Loire |
| Germany | Charite Universitaetsmedizin Berlin ( Site 0071) | Berlin | |
| Germany | Universitaetsklinikum Essen ( Site 0074) | Essen | Nordrhein-Westfalen |
| Germany | Medizinische Hochschule Hannover ( Site 0073) | Hannover | Niedersachsen |
| Hungary | Semmelweis Egyetem ( Site 0281) | Budapest | |
| Hungary | Debreceni Egyetem. ( Site 0283) | Debrecen | |
| Hungary | Pecsi Tudomanyegyetem AOK ( Site 0282) | Pecs | Baranya |
| Hungary | Szegedi Tudomanyegyetem ( Site 0284) | Szeged | Csongrad |
| Italy | IRCCS Ospedale San Raffaele di Milano ( Site 0098) | Milano | |
| Italy | Azienda Ospedaliera di Padova U.O.C. Trapianti Rene e Pancreas ( Site 0091) | Padova | Veneto |
| Italy | Policlinico Gemelli Instituto di Clinica Chirurgica ( Site 0093) | Roma | |
| Italy | A.O.U. Citta della Salute e della Scienza di Torino ( Site 0096) | Torino | Piemonte |
| Mexico | Centenario Hospital Miguel Hidalgo ( Site 0215) | Aguascalientes | |
| Mexico | Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0214) | Ciudad de Mexico | |
| Mexico | Instituto Mexicano de Trasplantes S C ( Site 0212) | Cuernavaca | Morelos |
| Mexico | Instituto Nacional de Cardiologia Ignacio Chavez ( Site 0213) | Mexico City | |
| Mexico | Faicic S de RL de CV ( Site 0211) | Veracruz | |
| New Zealand | Auckland City Hospital ( Site 0002) | Auckland | |
| Poland | Uniwersyteckie Centrum Kliniczne ( Site 0170) | Gdansk | Pomorskie |
| Poland | Szpital Wojewodzki w Poznaniu ( Site 0168) | Poznan | Wielkopolskie |
| Poland | Pomorski Uniwersytet Medyczny ( Site 0167) | Szczecin | Zachodniopomorskie |
| Poland | Szpital Kliniczny Dzieciatka Jezus ( Site 0165) | Warszawa | Mazowieckie |
| Poland | Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego ( Site 0162) | Wroclaw | Dolnoslaskie |
| Spain | Hospital Clinic i Provincial de Barcelona ( Site 0113) | Barcelona | |
| Spain | Hospital del Mar ( Site 0121) | Barcelona | La Coruna |
| Spain | Hospital Universitari Vall de Hebron ( Site 0112) | Barcelona | |
| Spain | Hospital Universitari de Bellvitge IDIBELL ( Site 0114) | L Hospitalet De Llobregat | La Coruna |
| Spain | Hospital Doce de Octubre ( Site 0116) | Madrid | |
| Spain | Hospital Universitario Miguel Servet ( Site 0118) | Zaragoza | |
| United Kingdom | Queen Elizabeth Hospital ( Site 0356) | Birmingham | |
| United Kingdom | St Georges University Hospitals NHS Foundation Trust. ( Site 0136) | London | London, City Of |
| United States | The Emory Clinic ( Site 0247) | Atlanta | Georgia |
| United States | Johns Hopkins Hospital ( Site 0232) | Baltimore | Maryland |
| United States | University of Maryland Medical Center ( Site 0234) | Baltimore | Maryland |
| United States | UAB ( Site 0269) | Birmingham | Alabama |
| United States | Brigham & Women's Hospital ( Site 0244) | Boston | Massachusetts |
| United States | Medical University of South Carolina ( Site 0257) | Charleston | South Carolina |
| United States | University of Chicago ( Site 0251) | Chicago | Illinois |
| United States | The Ohio State University Wexner Medical Center ( Site 0264) | Columbus | Ohio |
| United States | Henry Ford Hospital ( Site 0242) | Detroit | Michigan |
| United States | Duke University Medical Center ( Site 0243) | Durham | North Carolina |
| United States | Indiana University ( Site 0261) | Indianapolis | Indiana |
| United States | Saint Barnabas Medical Center ( Site 0250) | Livingston | New Jersey |
| United States | UCLA Medical Center ( Site 0266) | Los Angeles | California |
| United States | Vanderbilt University Medical Center ( Site 0275) | Nashville | Tennessee |
| United States | Ochsner Clinic Foundation ( Site 0238) | New Orleans | Louisiana |
| United States | Columbia University Medical Center ( Site 0255) | New York | New York |
| United States | Icahn School of Medicine at Mount Sinai ( Site 0256) | New York | New York |
| United States | New York Presbyterian Hospital - Weill Cornell Medical Center ( Site 0276) | New York | New York |
| United States | University of Nebraska Medical Center ( Site 0272) | Omaha | Nebraska |
| United States | University of Pennsylvania ( Site 0270) | Philadelphia | Pennsylvania |
| United States | University of Pittsburgh ( Site 0252) | Pittsburgh | Pennsylvania |
| United States | Virginia Commonwealth University ( Site 0245) | Richmond | Virginia |
| United States | UC Davis Medical Center ( Site 0271) | Sacramento | California |
| United States | University of California-San Francisco ( Site 0236) | San Francisco | California |
| United States | University of Washington Medical Center ( Site 0246) | Seattle | Washington |
| United States | Stanford Health Care ( Site 0235) | Stanford | California |
| United States | Wake Forest University Baptist Medical Center ( Site 0260) | Winston-Salem | North Carolina |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC |
United States, Argentina, Australia, Austria, Belgium, Canada, Colombia, France, Germany, Hungary, Italy, Mexico, New Zealand, Poland, Spain, United Kingdom,
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 Clin — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Percentage of Participants With Adjudicated Cytomegalovirus (CMV) Disease Through 52 Weeks Post-transplant | CMV disease was defined as the presence of either CMV end-organ disease or CMV syndrome and was confirmed by an independent, blinded Clinical Adjudication Committee (CAC). Only CAC-confirmed ("adjudicated") cases were included in percentage of participants who met the endpoint. Investigator-assessed cases which were not confirmed by the CAC were not included. | Up to 52 weeks | |
| Secondary | Percentage of Participants With Adjudicated CMV Disease Through 28 Weeks Post-transplant | CMV disease was defined as the presence of either CMV end-organ disease or CMV syndrome and was confirmed by an independent, blinded CAC. Only CAC-confirmed ("adjudicated") cases were included in percentage of participants who met the endpoint. Investigator-assessed cases which were not confirmed by the CAC were not included. | Up to 28 weeks | |
| Secondary | Time to Onset of Adjudicated CMV Disease Through 52 Weeks Post-transplant | The time to onset of adjudicated CMV disease was calculated in days, from the day of randomization to the day of onset of CMV disease as determined by the CAC. | Up to 52 weeks | |
| Secondary | Percentage of Participants With Any AE | An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. | Up to 52 weeks | |
| Secondary | Percentage of Participants With Any Drug-related Serious Adverse Event (SAE) | An SAE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event. SAEs that the investigator determined the relationship of the AE to the treatment as at least possibly related were reported. | Up to 52 weeks |
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