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

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.

Study Overview

• Status: Completed
• Conditions: Cytomegalovirus (CMV)
• Intervention / Treatment: Drug: Maribavir; Other: Placebo; Drug: Valganciclovir

• Study Type: Interventional
• Enrollment (Actual): 553
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Austria
  • Linz, Austria, 4020
    • Elisabethinen Hospital Linz
  • Wien
    • Vienna, Wien, Austria
      • Medizinische Universitat Wien (Medical University of Vienna)
• Belgium
  • Liège, Belgium, 4000
    • CHU de Liège
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • UZ Antwerpen
  • Brussels
    • Bruxelles, Brussels, Belgium, 1200
      • Cliniques Universitaires Saint-Luc
    • Bruxelles, Brussels, Belgium, 1000
      • Institute Jules Bordet
    • Jette, Brussels, Belgium, 1090
      • Universitair Ziekenhuis Brussel - PIN
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • University Hospital Gent
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
      • UZ Leuven
  • West-Vlaanderen
    • Brugge, West-Vlaanderen, Belgium, 8000
      • AZ Sint-Jan AV
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Queen Elizabeth II Health Sciences Center
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Hamilton Health Sciences Corporation
• China
  • Changsha, China, 410008
    • Xiangya Hospital Central South University
  • Guangzhou, China, 510180
    • Guangzhou First People's Hospital
  • Hangzhou Zhejiang, China, 310003
    • The First Affiliated Hospital, College of Medicine, Zhejiang University
  • Zhengzhou, China, 450008
    • Henan cancer hospital
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University First Hospital
    • Beijing, Beijing, China, 100044
      • Peking University People's Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital Southern Medical University
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University
• Croatia
  • Zagreb, Croatia, 10000
    • University Hospital Center Zagreb
• Czechia
  • Praha, Czechia, 128 20
    • Ustav hematologie a krevni transfuze
  • Praha, Hlavní Mesto
    • Prague, Praha, Hlavní Mesto, Czechia, 150 00
      • Fakultni nemocnice v Motole
• France
  • Besnçon, France, 25030
    • Hopital Jean Minjoz
  • Nice, France, 7120
    • Institut Paoli Calmettes
  • Paris, France, 75012
    • Hopital Saint Antoine
  • Paris, France, 75475
    • Hopital Saint Louis
  • Toulouse cedex 9, France, 31059
    • EDOG - Institut Claudius Regaud - PPDS
  • Bas-Rhin
    • Strasbourg Cedex, Bas-Rhin, France, 67033
      • Institut de cancerologie Strasbourg Europe
    • Strasbourg Cedex, Bas-Rhin, France, 67098
      • Hôpital de HAUTEPIERRE
  • Gironde
    • Pessac, Gironde, France, 33604
      • CHU de Bordeaux
  • Haute-Vienne
    • Limoges, Haute-Vienne, France, 87042
      • Hôpital Universitaire Dupuytren
  • Isère
    • GRENOBLE Cedex 9, Isère, France, 38043
      • CHU de Grenoble
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44093
      • Hotel Dieu
  • Maine-et-Loire
    • Angers Cedex 9, Maine-et-Loire, France, 49933
      • CHU Angers
  • Val-de-Marne
    • Créteil, Val-de-Marne, France, 94010
      • Hopital Henri Mondor
• Germany
  • Augsburg, Germany, 86156
    • Universitatsklinikum Augsburg
  • Berlin, Germany, 13125
    • Helios Klinikum Berlin-Buch
  • Halle, Germany, 6120
    • Martin Luther Universitat Halle Wittenberg
  • Hamburg, Germany, 20251
    • Universitatsklinikum Hamburg Eppendorf
  • Rostock, Germany
    • Universitätsklinik Rostock
  • Stuttgart, Germany, 70376
    • Robert Bosch Krankenhaus
  • Tübingen, Germany, 72076
    • Universitatsklinikum Tubingen
  • Nordrhein-Westfalen
    • Muenster, Nordrhein-Westfalen, Germany, 48149
      • Universitatsklinikum Munster
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
  • Saarland
    • Homburg, Saarland, Germany, 66424
      • Universität des Saarlandes
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • Universitätsklinikum Leipzig
• Greece
  • Thessaloniki, Greece, 57010
    • Georgios Papanikolaou General Hospital of Thessaloniki
  • Attiki
    • Athina, Attiki, Greece, 124 64
      • Attikon University General Hospital
• Hungary
  • Budapest, Hungary, 1097
    • Del-pesti Centrumkorhaz- Orszagos Hematologiai és Infektologiai Intezet
• Israel
  • Haifa, Israel, 31999
    • Rambam Medical Center - PPDS
  • Tel-Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center PPDS
  • HaMerkaz
    • Ramat Gan, HaMerkaz, Israel, 5262000
      • Sheba Medical Center - PPDS
  • Yerushalayim
    • Jerusalem, Yerushalayim, Israel, 90000
      • Hadassah Medical Center - PPDS
• Italy
  • Firenze, Italy, 50134
    • Azienda Ospedaliera Universitaria Careggi
  • Milano, Italy, 20122
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario A Gemelli
  • Torino, Italy, 10126
    • Azienda Ospedaliera Città della Salute e della Scienza di Torino
  • Lombardia
    • Brescia, Lombardia, Italy, 30174
      • Ospedale dell'Angelo
  • Piemonte
    • Torino, Piemonte, Italy, 10126
      • Ospedale Infantile Regina Margherita - INCIPIT - PIN
  • Veneto
    • Verona, Veneto, Italy, 37134
      • Azienda Ospedaliera Universitaria Integrata Di Verona
• Korea, Republic of
  • Busan, Korea, Republic of, 49201
    • Dong-A University Hospital
  • Daegu, Korea, Republic of, 41931
    • Keimyung University Dongsan Hospital
• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1023
      • Auckland City Hospital
  • South Island
    • Christchurch, South Island, New Zealand, 8011
      • Canterbury Health Laboratories
• Poland
  • Gdansk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 50-367
      • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-106
      • MTZ Clinical Research Sp z o o - PRATIA - PPDS
• Russian Federation
  • Irkutsk, Russian Federation, 664035
    • Regional Oncology Center
  • Kirov, Russian Federation, 610027
    • Kirov Research Institute of Haematology and Blood Transfusion
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 197022
      • First St. Petersburg State Medical University n.a. I.P Pavlov
• Singapore
  • Singapore, Singapore, 169608
    • Singapore General Hospital (SGH)
  • Singapore, Singapore, 119228
    • National University Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron - PPDS
  • Barcelona, Spain, 08908-
    • ICO l'Hospitalet Hospital Duran i Reynals
  • Cordoba, Spain, 14004
    • C.H. Regional Reina Sofia - PPDS
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de las Nieves
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta de Hierro - Majadahonda
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Malaga - Hospital General
  • San Sebastian Gipuzkoa, Spain, 20014
    • Hospital Universitario de Donostia
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitario Germans Trias i Pujol
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marqués de Valdecilla
  • Castilla Y León
    • Salamanca, Castilla Y León, Spain, 37007
      • Complejo Asistencial Universitario de Salamanca - H. Clinico
• Switzerland
  • Zurich, Switzerland, 8091
    • Universitätsspital Zürich
• Turkey
  • Adana, Turkey, 1250
    • Baskent University Medical Faculty Adana Practice and Research Center
  • Ankara, Turkey, 06590
    • Ankara University Medica Faculty Hematology Department Clinical Research Area PPDS
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust - PPDS
  • Southampton, United Kingdom, SO16 6YD
    • Southampton University Hospitals NHS Trust
  • Birmingham
    • West Midlands, Birmingham, United Kingdom, B9 5SS
      • Birmingham Heartlands Hospital
  • London
    • Tooting, London, United Kingdom, SW17 0QT
      • St George's Hospital
  • London, City Of
    • London, London, City Of, United Kingdom, W12 0HS
      • Hammersmith Hospital
    • London, London, City Of, United Kingdom, WC1E 6BT
      • University College London
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L7 8XP
      • Clatterbridge Cancer Centre Liverpool
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
    • Stanford, California, United States, 94305
      • Stanford University
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute - PPDS
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins Hospital
    • Baltimore, Maryland, United States, 21201
      • University of Maryland School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Womens Hospital
    • Worcester, Massachusetts, United States, 01655
      • UMASS Memorial Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Detroit, Michigan, United States, 48201
      • Harper University Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • University of Minnesota
    • Rochester, Minnesota, United States, 59905
      • Mayo Clinic - PIN
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10021
      • Joan and sandford I. Weill Medical College of Cornell University Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37203-1624
      • TriStar Centennial Medical center
  • Texas
    • Austin, Texas, United States, 78704
      • Saint Davids South Austin Medical Center
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • Texas Transplant Institute
  • Washington
    • Seattle, Washington, United States, 98108
      • VA Puget Sound Health Care System - NAVREF - PPDS
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • The Medical College of Wisconsin, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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:

  1. 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,
  2. Haploidentical donor
  3. Unrelated donor with at least 1 mismatch at 1 of the following 4 HLA -gene loci: HLA-A, -B, -C and -DRB1,
  4. Use of umbilical cord blood as stem cell source,
  5. Use of ex vivo T-cell-depleted grafts,
  6. 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):

  1. Absolute neutrophil count to >=1000 per cubic millimeter (/mm^3) [1.0*10^9/L].
  2. Platelet count >=25,000/mm^3 [25*10^9/L].
  3. Hemoglobin >=8 grams per deciliter (g/dL).
  4. Estimated creatinine clearance >=30 milliliters per minute (mL/min).
• Have a negative serum beta human chorionic gonadotropin (beta-HCG) pregnancy test at screening, if a female of child bearing potential. Urine pregnancy tests may be done per institutional requirements; however they are not sufficient for eligibility determination. Sexually active females of child bearing potential must agree to comply with any applicable contraceptive requirements of the protocol. If male, must agree to use an acceptable method of birth control, as defined in the protocol, during the study treatment administration period and for 90 days afterward the last dose of study treatment.
• Be able to swallow tablets.
• Have life expectancy of >=8 weeks.
• Weigh >=40 kilograms (kg).
• Be willing and have an understanding and ability to fully comply with study procedures and restrictions defined in the protocol.

Exclusion Criteria:

• 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.
• Have previously received maribavir.
• Have serum aspartate aminotransferase (AST) greater than (>) 5 times upper limit of normal (ULN) at screening, or serum alanine aminotransferase (ALT) >5 times ULN at screening, or total bilirubin >= 3.0*ULN at screening (except for documented Gilbert's syndrome), as analyzed by local or central laboratory.
• Have known (previously documented) positive results for human immunodeficiency virus (HIV). Participants must have a confirmed negative HIV test result within 3 months of study entry or, if unavailable, be tested by a local laboratory during the screening period.
• Have active malignancy with the exception of nonmelanoma skin cancer, as determined by the investigator. Participants who experience relapse or progression of their underlying malignancy (for which HSCT was performed), as determined by the investigator, are not to be enrolled.
• Be undergoing treatment for acute or chronic hepatitis C

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Valganciclovir 900 mg BID; Participants 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.	Other: Placebo; Participants will receive placebo tablets matched to either maribavir or valganciclovir.; Drug: Valganciclovir; Participants will receive valganciclovir tablets orally.
Experimental: Maribavir 400 mg BID; Participants received 400 mg of maribavir along with a placebo matched to valganciclovir, BID orally for 8 weeks.	Drug: Maribavir; Participants will receive 400 mg of maribavir BID orally.; Other: Placebo; Participants will receive placebo tablets matched to either maribavir or valganciclovir.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-Time Curve Over the 12-Hour Dosing Interval at Steady State AUC(0-tau) of Maribavir for Adolescent Participants Only		Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
Maximum Observed Plasma Concentration (Cmax) of Maribavir for Adolescent Participants Only		Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
Time When Maximum Concentration is Observed (Tmax) of Maribavir for Adolescent Participants Only		Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
Apparent Oral Clearance (CL/F) of Maribavir for Adolescent Participants Only		Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
Apparent Volume of Distribution (Vz/F) of Maribavir for Adolescent Participants Only		Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
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	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 this key secondary endpoint, the participant must have received exclusively study-assigned treatment (regardless of whether study-assigned treatment was completed). CMV Infection Symptom Control is defined as no new clinical findings of CMV tissue invasive disease. Maintenance of Treatment Effect is defined as maintaining confirmed CMV viremia clearance and CMV infection symptom control through 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	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 this secondary endpoint, the participant must have received exclusively study-assigned treatment for 8 weeks. Participants who discontinued treatment early were non-responders for this endpoint.	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	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 this secondary endpoint, the participant must have received exclusively study-assigned treatment for 8 weeks.	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	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 this secondary endpoint, the participant must have received exclusively study-assigned treatment (regardless of whether the 8-week study-assigned treatment was completed or discontinued early) and had no symptoms of tissue invasive CMV disease at Week 8, Week 8 through Week 12, and Week 8 through Week 20, respectively.	Week 8 through Weeks 12 and 20
Number of Participants With Confirmed Recurrence of Viremia During First 8 Weeks of the Study	Recurrence of CMV viremia is defined as plasma CMV DNA concentration greater than or equal to (>=) 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 plasma samples at least 5 days apart, after being unquantifiable (<LLOQ, i.e. <137 IU/mL) for at least 5 days in 2 consecutive samples during the first 8 weeks of the study, during the 12 weeks of the follow up study phase, and at any time during the study.	Up to Week 8
Number of Participants With Confirmed Recurrence of Viremia During the Follow-up Period	Recurrence of CMV viremia is defined as plasma CMV DNA concentration greater than or equal to (>=) LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive plasma samples at least 5 days apart, after being unquantifiable (<LLOQ) for at least 5 days in 2 consecutive samples during the first 8 weeks of the study, during the 12 weeks of the follow up study phase, and at any time during the study.	From Week 9 up to Week 20
Number of Participants With Confirmed Recurrence of Viremia at Any Time During the Study	Recurrence of CMV viremia is defined as plasma CMV DNA concentration greater than or equal to (>=) LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive plasma samples at least 5 days apart, after being unquantifiable (<LLOQ) for at least 5 days in 2 consecutive samples during the first 8 weeks of the study, during the 12 weeks of the follow up study phase, and at any time during the study.	Up to Week 20
Number of Participants With Confirmed Recurrence of Viremia While on Study Treatment and Off Treatment	Recurrence of CMV viremia is defined as plasma CMV DNA concentration greater than or equal to (>=) LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive plasma samples at least 5 days apart, after being unquantifiable (<LLOQ) for at least 5 days in 2 consecutive samples during the first 8 weeks of the study, during the 12 weeks of the follow up study phase, and at any time during the study.	Baseline up to Week 20
Number of Participants With Grade 3 or 4 (Shift From Baseline Grade <3) and Grade 4 Neutropenia (Shift From Baseline Grade <4) While on Study Treatment	Grade 3 and grade 4 neutropenia are defined as absolute neutrophil count (ANC) <1000 per cubic millimeter (/mm^3) and ANC <500/mm^3 respectively. Incidence of Grade 3 or 4 neutropenia represents the percentage of participants with Grade <3 (or missing) neutropenia at baseline, but Grade 3 or 4 while on study treatment. Incidence of Grade 4 neutropenia represents the number of participants with Grade <4 (or missing) neutropenia at baseline, but Grade 4 while on study treatment.	From start of study drug to end of study drug + 1 day (up to approximately Week 8)
Number of Participants With Treatment-Emergent Adverse Events During the On-Treatment Period	An adverse event (AE) is any untoward medical occurrence in a clinical investigation participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE that has a start date on or after the first dose of study treatment, or that has a start date before the date of first dose of study treatment but increases in severity after the first dose of study treatment, will be considered a treatment-emergent AE (TEAE).	From the start of the study treatment to 7 days after the last dose of study treatment (up to approximately Week 9)
Predose Concentration (Cmin) of Maribavir	The primary plasma maribavir concentration dataset (primary concentration dataset) includes all plasma maribavir concentrations. Missing PK sampling times are imputed according to the sparse sampling schedule in primary concentration dataset.	Weeks 1, 4, and 8: pre-morning dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Developing Resistance	Resistance was defined as the presence of any CMV resistance-associated amino acid substitution that has been documented (or suspected) to be associated with reduced susceptibility to conventional anti-CMV therapies (ganciclovir/valganciclovir, foscarnet, and cidofovir) or maribavir. Genotypic resistance analyses were restricted to sequence variants that were known or suspected to be associated with resistance to conventional anti-CMV therapies or maribavir as of January 21, 2022. A participant was categorized as having developed resistance if the central lab genotyping results indicated the presence of one or more treatment-emergent resistance mutations.	From start of study drug up to end of the study (up to Week 20)

Collaborators and Investigators

• Sponsor: Shire
• Collaborators: Takeda Development Center Americas, Inc.

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2017
• Primary Completion (Actual): July 1, 2022
• Study Completion (Actual): July 1, 2022

Study Registration Dates

• First Submitted: September 29, 2016
• First Submitted That Met QC Criteria: October 5, 2016
• First Posted (Estimate): October 6, 2016

Study Record Updates

• Last Update Posted (Estimate): March 3, 2023
• Last Update Submitted That Met QC Criteria: February 2, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Cytomegalovirus Infections; Anti-Infective Agents; Antiviral Agents; Valganciclovir; Maribavir
• Other Study ID Numbers: SHP620-302; 2015-004726-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No