A Study of Maribavir Compared to Valganciclovir to Treat Cytomegalovirus Infections in People Who Have Received Stem Cell Transplants
A Phase 3, Multicenter, Randomized, Double-blind, Double-dummy, Active-controlled Study to Assess the Efficacy and Safety of Maribavir Compared to Valganciclovir for the Treatment of Cytomegalovirus (CMV) Infection in Hematopoietic Stem Cell Transplant Recipients
2 other identifiers
interventional
553
22 countries
126
Brief Summary
This study is about treatment options for cytomegalovirus infections in people who have received stem cell transplants. The main aim of the study is to check if the cytomegalovirus infection can no longer be detected after treatment with marivabir or valganciclovir. Participants will take 2 tablets of marivabir or valganciclovir and 2 tablets of placebo twice a day for 8 weeks. A placebo will look like marivabir or valganciclovir but will not have any medicine in it. After treatment, each participant will be followed up for up to 12 weeks. Participants will visit their study clinic up to 18 times during the study.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Apr 2017
Longer than P75 for phase_3
126 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 29, 2016
CompletedFirst Posted
Study publicly available on registry
October 6, 2016
CompletedStudy Start
First participant enrolled
April 14, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2022
CompletedResults Posted
Study results publicly available
March 3, 2023
CompletedMarch 3, 2023
February 1, 2023
5.2 years
September 29, 2016
December 19, 2022
February 2, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants Who Achieved Confirmed Clearance of Plasma Cytomegalovirus (CMV) Deoxyribose Nucleic Acid (DNA) at the End of Study Week 8
Confirmed CMV viremia clearance is defined as plasma CMV DNA concentrations less than lower limit of quantification (LLOQ; i.e. \<137 International units per milliliter \[IU/mL\]), when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive post baseline samples separated by at least 5 days. To be considered a responder for the primary endpoint, the participant must have received exclusively study-assigned treatment (regardless of whether study-assigned treatment was completed).
Week 8
Secondary Outcomes (16)
Number of Participants Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control at the End of Week 8, Followed by Maintenance of Treatment Effect at Week 16
Week 8 up to Week 16
Number of Participants Who Achieved Confirmed Clearance of Plasma CMV DNA (CMV Viremia Clearance) at Week 8 After Receiving 8 Weeks of Study Assigned Treatment
Week 8
Number of Participants Who Achieved Confirmed CMV Viremia Clearance After Receiving 8 Weeks of Study-assigned Treatment Through Weeks 12, 16 and 20
Week 8 through Weeks 12, 16 and 20
Number of Participants Who Maintained Confirmed CMV Viremia Clearance at Week 8 After Receiving Study-Assigned Treatment Through Study Weeks 12 and 20 Regardless of Whether Study Assigned Treatment Was Completed
Week 8 through Weeks 12 and 20
Number of Participants With Confirmed Recurrence of Viremia During First 8 Weeks of the Study
Up to Week 8
- +11 more secondary outcomes
Other Outcomes (1)
Number of Participants Developing Resistance
From start of study drug up to end of the study (up to Week 20)
Study Arms (2)
Valganciclovir 900 mg BID
ACTIVE COMPARATORParticipants received 900 milligrams (mg) of valganciclovir along with a placebo matched to maribavir, twice daily (BID) orally for 8 weeks. Valganciclovir dose was allowed to be adjusted to 450 mg BID or 450 mg QD based on renal function impairment assessed at baseline or development of neutropenia during the study.
Maribavir 400 mg BID
EXPERIMENTALParticipants received 400 mg of maribavir along with a placebo matched to valganciclovir, BID orally for 8 weeks.
Interventions
Participants will receive placebo tablets matched to either maribavir or valganciclovir.
Eligibility Criteria
You may qualify if:
- Be able to provide written, personally signed, and dated informed consent to participate in the study before completing any study-related procedures. As applicable, a parent/both parents or legally authorized representative (LAR) must provide signature of informed consent and there must be documentation of assent by the participants before completing any study-related procedures. During the COVID-19 public health emergency, informed consent from a potential or current trial participant may, if permitted by local laws and regulations, be obtained via electronic informed consent (eIC) capabilities or an electronic face-to-face consent interview when these individuals are unable to travel to the site (FDA COVID-19 Guidance, 27 January 2021, Q11).
- Be greater than or equal to (\>=) 16 years of age at the time of consent.
- Be a recipient of hematopoietic stem cell transplant.
- Have a documented asymptomatic CMV infection, with a screening value of CMV DNA \>=1365 International Units per millilitre (IU/mL) to less than or equal to (\<=) 273000 IU/mL in whole blood or \>=455 IU/mL to \<=91000 IU/mL in plasma in 2 consecutive assessments, separated by at least 1 day, as determined by local or central specialty laboratory quantitative polymerase chain reaction (qPCR) or comparable quantitative CMV DNA results. Both samples should be taken within 14 days prior to randomization with second sample obtained within 5 days prior to randomization. Same laboratory and same sample type (whole blood or plasma) should be used for these assessments. Asymptomatic CMV infection is defined as an infection that does not present with tissue invasive CMV disease, as assessed by the investigator. Participants with CMV DNA less than (\<) 910 and \>=455 IU/mL in plasma or \<2730 and \>=1365 IU/mL in whole blood will also need to meet at least 1 of the following criteria for high-risk CMV infection to be eligible:
- Human leukocyte antigen (HLA)-related (sibling) donor with at least 1 mismatch at 1 of the following 3 HLA-gene loci: HLA-A, -B or -DR,
- Haploidentical donor
- Unrelated donor with at least 1 mismatch at 1 of the following 4 HLA -gene loci: HLA-A, -B, -C and -DRB1,
- Use of umbilical cord blood as stem cell source,
- Use of ex vivo T-cell-depleted grafts,
- Grade 2 or greater graft-versus-host-disease (GVHD), requiring the use of systemic corticosteroids (defined as the use of \>=1 milligram per kilogram per day (mg/kg/day) of prednisone or equivalent dose of another corticosteroid).
- Have the current CMV infection as the first episode of CMV viremia after HSCT, either primary or reactivation, which in the investigator's opinion requires treatment.
- Per investigator's judgment, be eligible for treatment with valganciclovir.
- Have all of the following results as part of screening laboratory assessments (results from either the central laboratory or a local laboratory can be used for qualification):
- Absolute neutrophil count to \>=1000 per cubic millimeter (/mm\^3) \[1.0\*10\^9/L\].
- Platelet count \>=25,000/mm\^3 \[25\*10\^9/L\].
- +7 more criteria
You may not qualify if:
- Have CMV tissue invasive disease as assessed by the investigator at the time of screening and randomization at Visit 2/Day 0.
- Have a CMV infection that is known to be genotypically resistant to ganciclovir, valganciclovir, foscarnet, or cidofovir based on documented evidence.
- Be presenting with recurrent CMV infection (defined as a new detection of CMV infection in a participants who had at least one previously documented episode of CMV infection post-transplant, and who has had at least 2 weeks of undetectable CMV DNA between the episodes during active surveillance, based on same local laboratory and same sample type). The Participants must also have been off any anti-CMV treatment between the current and prior infection. Otherwise, the current infection may be considered continuation of the prior infection.
- Require ganciclovir, valganciclovir, foscarnet, or cidofovir administration for conditions other than CMV when study treatment is initiated (example: herpes simplex virus \[HSV\] co-infection requiring use of any of these agents after the randomization) or would need a co-administration with maribavir for CMV infection.
- Be receiving leflunomide, letermovir, or artesunate when study treatment is initiated.
- Note: Participants who may be receiving leflunomide must discontinue the use at least 14 days prior to randomization at Visit 2/Day 0 and the first dose of study treatment. Participants receiving letermovir must discontinue use 3 days prior to first dose of study treatment. Participants receiving artesunate must discontinue the use prior to the first dose of study treatment.
- Be on treatment with anti-CMV agents (ganciclovir, valganciclovir, foscarnet or letermovir) for the current CMV infection for longer than 72 hours.
- Have known hypersensitivity to the active substance or to an excipient of the study treatments.
- Have severe vomiting, diarrhea, or other severe gastrointestinal illness within 24 hours prior to the first dose of study treatment that would preclude administration of oral medication.
- Require mechanical ventilation or vasopressors for hemodynamic support at the time of randomization.
- Be female and pregnant or nursing.
- Have previously completed, discontinued, or have been withdrawn from this study.
- Have received any investigational agent with known anti-CMV activity within 30 days before initiation of study treatment or CMV vaccine at any time.
- Have received any unapproved agent or device within 30 days before initiation of study treatment.
- Have any clinically significant medical or surgical condition that, in the investigator's opinion, could interfere with interpretation of study results, contraindicate the administration of the assigned study treatment, or compromise the safety or well-being of the participant.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Shirelead
- Takeda Development Center Americas, Inc.collaborator
Study Sites (129)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
UCLA Medical Center
Los Angeles, California, 90095, United States
Stanford University
Stanford, California, 94305, United States
Colorado Blood Cancer Institute - PPDS
Denver, Colorado, 80218, United States
Yale University School of Medicine
New Haven, Connecticut, 06520, United States
Emory University
Atlanta, Georgia, 30322, United States
University of Chicago
Chicago, Illinois, 60637, United States
Loyola University Medical Center
Maywood, Illinois, 60153, United States
University of Maryland School of Medicine
Baltimore, Maryland, 21201, United States
Johns Hopkins Hospital
Baltimore, Maryland, 21205, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115, United States
Brigham and Womens Hospital
Boston, Massachusetts, 02115, United States
UMass Memorial Medical Center
Worcester, Massachusetts, 01655, United States
Harper University Hospital
Detroit, Michigan, 48201, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
University of Minnesota
Minneapolis, Minnesota, 55454, United States
Mayo Clinic - PIN
Rochester, Minnesota, 59905, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Joan and sandford I. Weill Medical College of Cornell University Clinic
New York, New York, 10021, United States
Columbia University Medical Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
TriStar Centennial Medical Center
Nashville, Tennessee, 37203-1624, United States
Saint Davids South Austin Medical Center
Austin, Texas, 78704, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Texas Transplant Institute
San Antonio, Texas, 78229, United States
VA Puget Sound Health Care System - NAVREF - PPDS
Seattle, Washington, 98108, United States
The Medical College of Wisconsin, Inc.
Milwaukee, Wisconsin, 53226, United States
Westmead Hospital
Westmead, New South Wales, 2145, Australia
Royal Adelaide Hospital
Adelaide, South Australia, 5000, Australia
Royal Melbourne Hospital
Parkville, Victoria, 3050, Australia
Medizinische Universitat Wien (Medical University of Vienna)
Vienna, Vienna, Austria
Elisabethinen Hospital Linz
Linz, 4020, Austria
UZ Antwerpen
Edegem, Antwerpen, 2650, Belgium
Institute Jules Bordet
Brussels, Brussels Capital, 1000, Belgium
Cliniques Universitaires Saint-Luc
Brussels, Brussels Capital, 1200, Belgium
Universitair Ziekenhuis Brussel - PIN
Jette, Brussels Capital, 1090, Belgium
University Hospital Gent
Ghent, Oost-Vlaanderen, 9000, Belgium
UZ Leuven
Leuven, Vlaams Brabant, 3000, Belgium
AZ Sint-Jan AV
Bruges, West-Vlaanderen, 8000, Belgium
CHU de Liège
Liège, 4000, Belgium
Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M9, Canada
Queen Elizabeth II Health Sciences Center
Halifax, Nova Scotia, B3H 2Y9, Canada
Hamilton Health Sciences Corporation
Hamilton, Ontario, L8N 3Z5, Canada
Peking University First Hospital
Beijing, Beijing Municipality, 100034, China
Peking University People's Hospital
Beijing, Beijing Municipality, 100044, China
Nanfang Hospital Southern Medical University
Guangzhou, Guangdong, 510515, China
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215006, China
Xiangya Hospital Central South University
Changsha, 410008, China
Guangzhou First People's Hospital
Guangzhou, 510180, China
The First Affiliated Hospital, College of Medicine, Zhejiang University
Hangzhou Zhejiang, 310003, China
Henan Cancer Hospital
Zhengzhou, 450008, China
University Hospital Center Zagreb
Zagreb, 10000, Croatia
Fakultni nemocnice v Motole
Prague, Praha, Hlavní Mesto, 150 00, Czechia
Ustav hematologie a krevni transfuze
Prague, 128 20, Czechia
Institut de Cancérologie Strasbourg Europe
Strasbourg, Bas-Rhin, 67033, France
Hopital de Hautepierre
Strasbourg, Bas-Rhin, 67098, France
CHU de Bordeaux
Pessac, Gironde, 33604, France
Hôpital Universitaire Dupuytren
Limoges, Haute-Vienne, 87042, France
CHU de GRENOBLE
Grenoble, Isère, 38043, France
Hôtel Dieu
Nantes, Loire-Atlantique, 44093, France
CHU Angers
Angers, Maine-et-Loire, 49933, France
Hopital Henri Mondor
Créteil, Val-de-Marne, 94010, France
Hopital Jean Minjoz
Besnçon, 25030, France
Institut Paoli Calmettes
Nice, 7120, France
Hôpital Saint Antoine
Paris, 75012, France
Hôpital Saint Louis
Paris, 75475, France
EDOG - Institut Claudius Regaud - PPDS
Toulouse, 31059, France
Universitätsklinikum Münster
Münster, North Rhine-Westphalia, 48149, Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, Rhineland-Palatinate, 55131, Germany
Universität des Saarlandes
Homburg, Saarland, 66424, Germany
Universitatsklinikum Leipzig
Leipzig, Saxony, 04103, Germany
Universitätsklinikum Augsburg
Augsburg, 86156, Germany
Helios Klinikum Berlin-Buch
Berlin, 13125, Germany
Martin Luther Universitat Halle Wittenberg
Halle, 6120, Germany
Universitätsklinikum Hamburg Eppendorf
Hamburg, 20251, Germany
Universitätsklinik Rostock
Rostock, Germany
Robert Bosch Krankenhaus
Stuttgart, 70376, Germany
Universitätsklinikum Tübingen
Tübingen, 72076, Germany
Attikon University General Hospital
Athens, Attica, 124 64, Greece
Georgios Papanikolaou General Hospital of Thessaloniki
Thessaloniki, 57010, Greece
Del-pesti Centrumkorhaz- Orszagos Hematologiai és Infektologiai Intezet
Budapest, 1097, Hungary
Sheba Medical Center - PPDS
Ramat Gan, Central District, 5262000, Israel
Hadassah Medical Center - PPDS
Jerusalem, Jerusalem, 90000, Israel
Rambam Medical Center - PPDS
Haifa, 31999, Israel
Tel Aviv Sourasky Medical Center PPDS
Tel Aviv, 64239, Israel
Ospedale Dell'Angelo
Brescia, Lombardy, 30174, Italy
Ospedale Infantile Regina Margherita - INCIPIT - PIN
Turin, Piedmont, 10126, Italy
Azienda Ospedaliera Universitaria Integrata Di Verona
Verona, Veneto, 37134, Italy
Azienda Ospedaliera Universitaria Careggi
Florence, 50134, Italy
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
Milan, 20122, Italy
Fondazione Policlinico Universitario A Gemelli
Roma, 00168, Italy
Azienda Ospedaliera Città della Salute e della Scienza di Torino
Torino, 10126, Italy
Auckland City Hospital
Grafton, Auckland, 1023, New Zealand
Canterbury Health Laboratories
Christchurch, South Island, 8011, New Zealand
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
Wroclaw, Lower Silesian Voivodeship, 50-367, Poland
MTZ Clinical Research Sp z o o - PRATIA - PPDS
Warsaw, Masovian Voivodeship, 02-106, Poland
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-214, Poland
First St. Petersburg State Medical University n.a. I.P Pavlov
Saint Petersburg, Sankt-Peterburg, 197022, Russia
Regional Oncology Center
Irkutsk, 664035, Russia
Kirov Research Institute of Haematology and Blood Transfusion
Kirov, 610027, Russia
National University Hospital
Singapore, 119228, Singapore
Singapore General Hospital (SGH)
Singapore, 169608, Singapore
Dong-A University Hospital
Busan, 49201, South Korea
Keimyung University Dongsan Hospital
Daegu, 41931, South Korea
Hospital Universitario Germans Trias i Pujol
Badalona, Barcelona, 08916, Spain
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, 39008, Spain
Complejo Asistencial Universitario de Salamanca - H. Clinico
Salamanca, Castille and León, 37007, Spain
Hospital Universitario Vall d'Hebrón - PPDS
Barcelona, 08035, Spain
ICO l'Hospitalet Hospital Duran i Reynals
Barcelona, 08908-, Spain
C.H. Regional Reina Sofia - PPDS
Córdoba, 14004, Spain
Hospital Universitario Virgen de Las Nieves
Granada, 18014, Spain
Hospital Universitario de La Princesa
Madrid, 28006, Spain
Hospital Universitario Ramon y Cajal
Madrid, 28034, Spain
Hospital Universitario Puerta de Hierro - Majadahonda
Madrid, 28222, Spain
Hospital Regional Universitario de Malaga - Hospital General
Málaga, 29010, Spain
Hospital Universitario de Donostia
San Sebastian Gipuzkoa, 20014, Spain
Hospital Clinico Universitario de Valencia
Valencia, 46010, Spain
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, 46026, Spain
Universitätsspital Zürich
Zurich, 8091, Switzerland
Baskent University Medical Faculty Adana Practice and Research Center
Adana, 1250, Turkey (Türkiye)
Ankara University Medica Faculty Hematology Department Clinical Research Area PPDS
Ankara, 06590, Turkey (Türkiye)
Birmingham Heartlands Hospital
West Midlands, Birmingham, B9 5SS, United Kingdom
Hammersmith Hospital
London, London, City of, W12 0HS, United Kingdom
University College London
London, London, City of, WC1E 6BT, United Kingdom
St George's Hospital
Tooting, London, SW17 0QT, United Kingdom
Clatterbridge Cancer Centre Liverpool
Liverpool, Merseyside, L7 8XP, United Kingdom
The Christie NHS Foundation Trust - PPDS
Manchester, M20 4BX, United Kingdom
Southampton University Hospitals NHS Trust
Southampton, SO16 6YD, United Kingdom
Related Publications (3)
Chou S, Winston DJ, Avery RK, Cordonnier C, Duarte RF, Haider S, Maertens J, Peggs KS, Solano C, Young JH, Gu J, Pocock G, Papanicolaou GA. Comparative Emergence of Maribavir and Ganciclovir Resistance in a Randomized Phase 3 Clinical Trial for Treatment of Cytomegalovirus Infection. J Infect Dis. 2025 Mar 17;231(3):e470-e477. doi: 10.1093/infdis/jiae469.
PMID: 39302855DERIVEDPapanicolaou GA, Avery RK, Cordonnier C, Duarte RF, Haider S, Maertens J, Peggs KS, Solano C, Young JH, Fournier M, Murray RA, Wu J, Winston DJ; AURORA Trial Investigators. Treatment for First Cytomegalovirus Infection Post-Hematopoietic Cell Transplant in the AURORA Trial: A Multicenter, Double-Blind, Randomized, Phase 3 Trial Comparing Maribavir With Valganciclovir. Clin Infect Dis. 2024 Mar 20;78(3):562-572. doi: 10.1093/cid/ciad709.
PMID: 38036487DERIVEDStewart AG, Kotton CN. What's New: Updates on Cytomegalovirus in Solid Organ Transplantation. Transplantation. 2024 Apr 1;108(4):884-897. doi: 10.1097/TP.0000000000004855. Epub 2023 Oct 30.
PMID: 37899366DERIVED
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Takeda
Study Officials
- STUDY DIRECTOR
Study Director
Shire
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 29, 2016
First Posted
October 6, 2016
Study Start
April 14, 2017
Primary Completion
July 1, 2022
Study Completion
July 1, 2022
Last Updated
March 3, 2023
Results First Posted
March 3, 2023
Record last verified: 2023-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Access Criteria
- IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.