A Study of Maribavir Compared to Valganciclovir to Treat Cytomegalovirus Infections in People Who Have Received Stem Cell Transplants

Cytomegalovirus (CMV) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02927067
• Other study ID #: SHP620-302
• Secondary ID: 2015-004726-34
• Status: Completed
• Phase: Phase 3
• Start date: April 14, 2017
• Est. completion date: July 1, 2022

Study information

• Verified date: February 2023
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 553
• Est. completion date: July 1, 2022
• Est. primary completion date: July 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cytomegalovirus (CMV)
• Cytomegalovirus Infections

Intervention

Drug:
• Maribavir
Participants will receive 400 mg of maribavir BID orally.
• Valganciclovir
Participants will receive valganciclovir tablets orally.

Other:
• Placebo
Participants will receive placebo tablets matched to either maribavir or valganciclovir.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Westmead Hospital	Westmead	New South Wales
Austria	Elisabethinen Hospital Linz	Linz
Austria	Medizinische Universitat Wien (Medical University of Vienna)	Vienna	Wien
Belgium	AZ Sint-Jan AV	Brugge	West-Vlaanderen
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles	Brussels
Belgium	Institute Jules Bordet	Bruxelles	Brussels
Belgium	UZ Antwerpen	Edegem	Antwerpen
Belgium	University Hospital Gent	Gent	Oost-Vlaanderen
Belgium	Universitair Ziekenhuis Brussel - PIN	Jette	Brussels
Belgium	UZ Leuven	Leuven	Vlaams Brabant
Belgium	CHU de Liège	Liège
Canada	Queen Elizabeth II Health Sciences Center	Halifax	Nova Scotia
Canada	Hamilton Health Sciences Corporation	Hamilton	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
China	Peking University First Hospital	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	Xiangya Hospital Central South University	Changsha
China	Guangzhou First People's Hospital	Guangzhou
China	Nanfang Hospital Southern Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital, College of Medicine, Zhejiang University	Hangzhou Zhejiang
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Henan Cancer Hospital	Zhengzhou
Croatia	University Hospital Center Zagreb	Zagreb
Czechia	Fakultni nemocnice v Motole	Prague	Praha, Hlavní Mesto
Czechia	Ustav hematologie a krevni transfuze	Praha
France	CHU Angers	Angers Cedex 9	Maine-et-Loire
France	Hopital Jean Minjoz	Besnçon
France	Hopital Henri Mondor	Créteil	Val-de-Marne
France	CHU de GRENOBLE	GRENOBLE Cedex 9	Isère
France	Hôpital Universitaire Dupuytren	Limoges	Haute-Vienne
France	Hôtel Dieu	Nantes	Loire-Atlantique
France	Institut Paoli Calmettes	Nice
France	Hôpital Saint Antoine	Paris
France	Hôpital Saint Louis	Paris
France	CHU de Bordeaux	Pessac	Gironde
France	Hopital de Hautepierre	Strasbourg Cedex	Bas-Rhin
France	Institut de Cancérologie Strasbourg Europe	Strasbourg Cedex	Bas-Rhin
France	EDOG - Institut Claudius Regaud - PPDS	Toulouse cedex 9
Germany	Universitätsklinikum Augsburg	Augsburg
Germany	Helios Klinikum Berlin-Buch	Berlin
Germany	Martin Luther Universitat Halle Wittenberg	Halle
Germany	Universitätsklinikum Hamburg Eppendorf	Hamburg
Germany	Universität des Saarlandes	Homburg	Saarland
Germany	Universitatsklinikum Leipzig	Leipzig	Sachsen
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz	Rheinland-Pfalz
Germany	Universitätsklinikum Münster	Muenster	Nordrhein-Westfalen
Germany	Universitätsklinik Rostock	Rostock
Germany	Robert Bosch Krankenhaus	Stuttgart
Germany	Universitätsklinikum Tübingen	Tübingen
Greece	Attikon University General Hospital	Athina	Attiki
Greece	Georgios Papanikolaou General Hospital of Thessaloniki	Thessaloniki
Hungary	Del-pesti Centrumkorhaz- Orszagos Hematologiai és Infektologiai Intezet	Budapest
Israel	Rambam Medical Center - PPDS	Haifa
Israel	Hadassah Medical Center - PPDS	Jerusalem	Yerushalayim
Israel	Sheba Medical Center - PPDS	Ramat Gan	HaMerkaz
Israel	Tel Aviv Sourasky Medical Center PPDS	Tel-Aviv
Italy	Ospedale Dell'Angelo	Brescia	Lombardia
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico	Milano
Italy	Fondazione Policlinico Universitario A Gemelli	Roma
Italy	Azienda Ospedaliera Città della Salute e della Scienza di Torino	Torino
Italy	Ospedale Infantile Regina Margherita - INCIPIT - PIN	Torino	Piemonte
Italy	Azienda Ospedaliera Universitaria Integrata Di Verona	Verona	Veneto
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu
New Zealand	Canterbury Health Laboratories	Christchurch	South Island
New Zealand	Auckland City Hospital	Grafton	Auckland
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	MTZ Clinical Research Sp z o o - PRATIA - PPDS	Warszawa	Mazowieckie
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu	Wroclaw	Dolnoslaskie
Russian Federation	Regional Oncology Center	Irkutsk
Russian Federation	Kirov Research Institute of Haematology and Blood Transfusion	Kirov
Russian Federation	First St. Petersburg State Medical University n.a. I.P Pavlov	Saint Petersburg	Sankt-Peterburg
Singapore	National University Hospital	Singapore
Singapore	Singapore General Hospital (SGH)	Singapore
Spain	Hospital Universitario Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Universitario Vall d'Hebrón - PPDS	Barcelona
Spain	ICO l'Hospitalet Hospital Duran i Reynals	Barcelona
Spain	C.H. Regional Reina Sofia - PPDS	Cordoba
Spain	Hospital Universitario Virgen de Las Nieves	Granada
Spain	Hospital Universitario de La Princesa	Madrid
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Regional Universitario de Malaga - Hospital General	Málaga
Spain	Complejo Asistencial Universitario de Salamanca - H. Clinico	Salamanca	Castilla Y León
Spain	Hospital Universitario de Donostia	San Sebastian Gipuzkoa
Spain	Hospital Universitario Marques de Valdecilla	Santander	Cantabria
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Switzerland	Universitätsspital Zürich	Zurich
Turkey	Baskent University Medical Faculty Adana Practice and Research Center	Adana
Turkey	Ankara University Medica Faculty Hematology Department Clinical Research Area PPDS	Ankara
United Kingdom	Clatterbridge Cancer Centre Liverpool	Liverpool	Merseyside
United Kingdom	Hammersmith Hospital	London	London, City Of
United Kingdom	University College London	London	London, City Of
United Kingdom	The Christie NHS Foundation Trust - PPDS	Manchester
United Kingdom	Southampton University Hospitals NHS Trust	Southampton
United Kingdom	St George's Hospital	Tooting	London
United Kingdom	Birmingham Heartlands Hospital	West Midlands	Birmingham
United States	Emory University	Atlanta	Georgia
United States	Saint Davids South Austin Medical Center	Austin	Texas
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Womens Hospital	Boston	Massachusetts
United States	University of Chicago	Chicago	Illinois
United States	Colorado Blood Cancer Institute - PPDS	Denver	Colorado
United States	Harper University Hospital	Detroit	Michigan
United States	Henry Ford Health System	Detroit	Michigan
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	UCLA Medical Center	Los Angeles	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	The Medical College of Wisconsin, Inc.	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	TriStar Centennial Medical Center	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Joan and sandford I. Weill Medical College of Cornell University Clinic	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic - PIN	Rochester	Minnesota
United States	Texas Transplant Institute	San Antonio	Texas
United States	VA Puget Sound Health Care System - NAVREF - PPDS	Seattle	Washington
United States	Stanford University	Stanford	California
United States	UMass Memorial Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Shire	Takeda Development Center Americas, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  China,  Croatia,  Czechia,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Korea, Republic of,  New Zealand,  Poland,  Russian Federation,  Singapore,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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 (	Up to Week 8
Secondary	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 (	From Week 9 up to Week 20
Secondary	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 (	Up to Week 20
Secondary	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 (	Baseline up to Week 20
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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