Efficacy and Safety Study of Maribavir Treatment Compared to Investigator-assigned Treatment in Transplant Recipients With Cytomegalovirus (CMV) Infections That Are Refractory or Resistant to Treatment With Ganciclovir, Valganciclovir, Foscarnet, or Cidofovir

Cytomegalovirus (CMV) Clinical Trial

Official title:

A Phase 3, Multicenter, Randomized, Open-label, Active-controlled Study to Assess the Efficacy and Safety of Maribavir Treatment Compared to Investigator-assigned Treatment in Transplant Recipients With Cytomegalovirus (CMV) Infections That Are Refractory or Resistant to Treatment With Ganciclovir, Valganciclovir, Foscarnet, or Cidofovir

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02931539
• Other study ID #: SHP620-303
• Secondary ID: 2015-004725-13
• Status: Completed
• Phase: Phase 3
• Start date: December 22, 2016
• Est. completion date: August 17, 2020

Study information

• Verified date: September 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the efficacy of maribavir to investigator-assigned anti-Cytomegalovirus (CMV) therapy in CMV viremia clearance in transplant recipients who are refractory or resistant to prior anti-CMV treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 352
• Est. completion date: August 17, 2020
• Est. primary completion date: August 17, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

1. The participant must 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 participant before completing any study-related procedures.

2. The participant must be a recipient of hematopoietic stem cell or solid organ transplant.

3. The participant must have a documented CMV infection in whole blood or plasma, with a screening value of greater than or equal to (>=) 2730 international units per milliliter (IU/mL) in whole blood or >= 910 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. The same laboratory and same sample type (whole blood or plasma) must be used for these assessments.

4. The participant must have a current CMV infection that is refractory to the most recently administered of the four anti-CMV treatment agents. Refractory is defined as documented failure to achieve greater than (>) 1 log10 (common logarithm to base 10) decrease in CMV DNA level in whole blood or plasma after a 14 day or longer treatment period with intravenous (IV) ganciclovir/oral valganciclovir, IV foscarnet, or IV cidofovir.

a. Participants with documentation of 1 or more CMV genetic mutations associated with resistance to ganciclovir/valganciclovir, foscarnet, and/or cidofovir must also meet the definition of refractory CMV infection.

5. The Investigator must be willing to treat the participant with at least one of the available anti-CMV drugs (ganciclovir, valganciclovir, foscarnet, or cidofovir). Note: Combination therapy with foscarnet and cidofovir is not permitted in the investigator-assigned anti-CMV treatment (IAT) arm due to the potential for serious nephrotoxicity.

6. The participant must be >= 12 years of age at the time of consent.

7. The participant must weigh >= 35 kilogram (kg).

8. The participant must 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 (ANC) >= 1000/ millimeter cube (mm^3) (1.0 x 10^9/liter [L])

2. Platelet count >= 25,000/mm^3 [25 x 10^9/L],

3. Hemoglobin >= 8 grams per deciliter (g/dL).

4. Estimated glomerular filtration rate (eGFR) > 30 (milliliters per minute (mL/min) /1.73 square meter (m^2) as assessed by Modification of Diet in Renal Disease (MDRD) formula for participants >= 18 years of age or Schwartz formula for participants less than (<) 18 years of age.

9. The participant must have a negative serum beta-human chorionic gonadotropin (beta-HCG) pregnancy test at screening, if a female of child bearing potential. Additional urine pregnancy tests may be done per institutional requirements. 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 if treated with maribavir, ganciclovir, valganciclovir, or cidofovir and for 180 days afterward if treated with foscarnet.

10. The participant must be able to swallow tablets, or receive tablets crushed and/or dispensed in water via nasogastric or orogastric tube.

11. The participant must be willing and have an understanding and ability to fully comply with study procedures and restrictions defined in the protocol.

12. The participant must be willing to provide necessary samples (example [e.g,] biopsy) for the diagnosis of tissue invasive CMV disease at baseline as determined by the Investigator.

13. The participant must have a life expectancy of >= 8 weeks.

Exclusion Criteria:

1. Have a current CMV infection that is considered refractory or resistant due to inadequate adherence to prior anti-CMV treatment, to the best knowledge of the Investigator.

2. Require ganciclovir, valganciclovir, foscarnet, or cidofovir administration for conditions other than CMV when study treatment is initiated (example: herpes simplex virus (HSV) coinfection requiring use of any of these agents after the randomization) or would need a coadministration with maribavir for CMV infection. NOTE: A participant who is not continuing with the same anti-CMV drug(s) (ganciclovir, valganciclovir or foscarnet) for the study treatment (if randomized to the investigator assigned anti-CMV treatment arm), must discontinue their use before the first dose of study drug. If participant is currently being treated with cidofovir and is assigned another anti-CMV therapy by the investigator, the participant must discontinue its use at least 14 days prior to randomization at Visit 2/Day 0 and the first dose of study treatment.

3. Be receiving leflunomide, letermovir, or artesunate when study treatment is initiated. NOTE: Participants 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 at least 3 days prior to the first dose of study treatment. Participants receiving artesunate must discontinue the use prior to the first dose of study treatment.

4. 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/enteral medication.

5. Have known hypersensitivity to the active substance or to an excipient for a study treatment.

6. Have tissue invasive CMV disease with central nervous system involvement including the retina (example, CMV retinitis).

7. Have serum aspartate aminotransferase (AST) > 5 times upper limit of normal (ULN) at screening, or serum alanine aminotransferase (ALT) > 5 times ULN at screening, or total bilirubin >= 3.0 x ULN at screening (except for documented Gilbert's syndrome), by local or central lab. Participants with biopsy confirmed CMV hepatitis will not be excluded from study participation despite AST or ALT > 5 times ULN at screening.

8. Have known 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.

9. Require mechanical ventilation or vasopressors for hemodynamic support at the time of enrollment.

10. Be female and pregnant or breast feeding.

11. Have previously received maribavir.

12. Have received any investigational agent with known anti-CMV activity within 30 days before initiation of study treatment or investigational CMV vaccine at any time.

13. Have received any unapproved agent or device within 30 days before initiation of study treatment.

14. Have active malignancy with the exception of nonmelanoma skin cancer. Participants who have had a hematopoietic stem cell transplant (HSCT) and who experience relapse or progression of the malignancy as per investigator's opinion are not to be enrolled.

15. Be undergoing treatment for acute or chronic hepatitis C.

16. Have any clinically significant medical or surgical condition that, in the investigator's opinion, could interfere with the interpretation of study results, contraindicate the administration of the assigned study treatment, or compromise the safety or well-being of the participant.

Related Conditions & MeSH terms

• Cytomegalovirus (CMV)
• Infections

Intervention

Drug:
• Maribavir
Maribavir 400 milligrams (mg) (2x200 mg tablets) will be administered twice daily for 8 weeks.
• Ganciclovir
Ganciclovir as per the investigator's prescribed dosing regimen will be administered for 8 weeks.
• Valganciclovir
Valganciclovir as per the investigator's prescribed dosing regimen will be administered for 8 weeks.
• Foscarnet
Foscarnet as per the investigator's prescribed dosing regimen will be administered for 8 weeks.
• Cidofovir
Cidofovir as per the investigator's prescribed dosing regimen will be administered for 8 weeks.

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital	Brisbane
Australia	Monash Health, Monash Medical Centre	Clayton	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Washington
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Westmead Hospital	Westmead	New South Wales
Austria	Tiroler Landeskrankenanstalten GmbH	Innsbruck
Austria	Allgemeines Krankenhaus der Stadt Wien	Wien
Belgium	ZNA Stuivenberg	Antwerpen
Belgium	AZ Sint-Jan AV	Brugge	West-Vlaanderen
Belgium	UZ Brussel	Brussels
Belgium	Hôpital Erasme	Bruxelles
Belgium	Institut Jules Bordet	Bruxelles	Brussels
Belgium	UZ Antwerpen	Edegem	Antwerpen
Belgium	UZ Gent	Gent	Oost-Vlaanderen
Belgium	UZ Leuven	Leuven	Vlaams Brabant
Canada	University of Alberta	Edmonton	Alberta
Canada	Hamilton Health Sciences Corporation	Hamilton	Ontario
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario
Canada	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec
Canada	McGill University Health Center	Montreal	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario
Croatia	University Hospital Center Zagreb	Zagreb
Denmark	Copenhagen University Hospital	København Ø	Capital
France	CHU Amiens Hôpital Sud	Amiens
France	CHU Amiens Hôpital Sud	AMIENS Cedex 1
France	CHRU Brest - Hospital Cavale Blanche	Brest	Finistère
France	Hopital Gabriel Montpied	Clermont-Ferrand
France	Hopital Henri Mondor	Créteil	Val-de-Marne
France	CHU de GRENOBLE	Grenoble
France	CHRU Lille	Lille Cedex
France	CHU Dupuytren	Limoges Cedex
France	Groupement Hospitalier Edouard Herriot	Lyon
France	Hôpital de La Croix Rousse	Lyon	Rhône
France	CHRU Nantes	Nantes	Loire-Atlantique
France	Groupe Hospitalier Necker Enfants Malades	Paris
France	Hôpital Saint Antoine	Paris
France	Hôpital Saint Louis	Paris
France	Centre Hospitalier Lyon Sud	Pierre-bénite	Rhône
France	CHRU de Poitiers La Miletrie	Poitiers
France	CHRU Rennes	Rennes	Ille-et-Vilaine
France	Institut de Cancerologie de la Loire	Saint-Priest en Jarez
France	Hopital de Hautepierre	Strasbourg
France	Hôpital Civil	STRASBOURG Cedex
France	Hopital Foch	Suresnes	Hauts-de-Seine
France	Hôpital de Rangueil	Toulouse	Haute-Garonne
France	CHRU Bretonneau	Tours	Indre-et-Loire
France	Hôpital Paul Brousse	Villejuif	Val-de-Marne
Germany	Universitätsklinikum Erlangen	Erlangen	Bayern
Germany	Universitätsklinikum Erlangen	Erlangen
Germany	Universitätsklinikum Essen	Essen	Nordrhein-Westfalen
Germany	University Clinic Heidelberg - PPDS	Heidelberg	Baden-Württemberg
Germany	University Clinic Heidelberg - PPDS	Heidelberg
Germany	Universitatsklinikum Leipzig	Leipzig	Sachsen
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz	Rheinland-Pfalz
Germany	LMU Klinikum der Universität München	München
Germany	Universitätsklinikum Tübingen	Tübingen
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi	Ancona	Marche
Italy	Istituto Europeo Di Oncologia	Milano	Lombardia
Italy	Ospedale San Raffaele S.r.l. - PPDS	Milano	Lombardia
Italy	Azienda Ospedaliero Universitaria di Parma	Parma
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Fondazione Policlinico Universitario A Gemelli	Roma
Italy	Azienda Sanitaria Universitaria Integrata di Udine	Udine
Singapore	Singapore General Hospital (SGH)	Singapore
Spain	Hospital Universitario Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Universitario de Cruces	Barakaldo
Spain	Fundacio Puigvert	Barcelona
Spain	Hospital de La Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Vall d'Hebrón - PPDS	Barcelona
Spain	Hospital Universitario de Bellvitge	L'Hospitalet de Llobregat
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Madrid
Spain	Complejo Asistencial Universitario de Salamanca - H. Clinico	Salamanca
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne	Vaud (fr)
United Kingdom	University Hospital Coventry	Coventry	Birmingham
United Kingdom	Beatson West of Scotland Cancer Centre - PPDS	Glasgow	Glasgow City
United Kingdom	Royal Liverpool and Broadgreen University Hospitals NHS Trust	Liverpool
United Kingdom	Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital	London
United Kingdom	Imperial College Healthcare NHS Trust	London	London, City Of
United Kingdom	Royal Free Hospital	London
United Kingdom	Manchester Royal Infirmary - PPDS	Manchester
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Sheffield Childrens Hospital	Sheffield	Yorkshire
United Kingdom	Birmingham Heartlands Hospital	West Midlands	Birmingham
United Kingdom	Wythenshawe Hospital - PPDS	Wythenshawe	Manchester
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University Hospital	Atlanta	Georgia
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Brigham and Womens Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Medical University of South Carolina - PPDS	Charleston	South Carolina
United States	Feinberg School of Medicine Northwestern University	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center - PIN	Cincinnati	Ohio
United States	The Christ Hospital	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Baylor All Saints Medical Center	Fort Worth	Texas
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Baylor College of Medicine	Houston	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Kentucky	Lexington	Kentucky
United States	UCLA Medical Center	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	University of Chicago Medical Center	Maywood	Illinois
United States	St Jude Children's Research Hospital	Memphis	Tennessee
United States	University of Minnesota	Minneapolis	Minnesota
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	New York Presbyterian Hospital - Weill-Cornell	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	AdventHealth	Orlando	Florida
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Mayo Clinic - PPDS	Rochester	Minnesota
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	UC Davis Medical Center	Sacramento	California
United States	University of Utah Health Sciences Center - PPDS	Salt Lake City	Utah
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Stanford University	Stanford	California
United States	SUNY Upstate Medical Center	Syracuse	New York
United States	University of Arizona	Tucson	Arizona
United States	UMass Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Croatia,  Denmark,  France,  Germany,  Italy,  Singapore,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Achieved Confirmed Clearance of Plasma Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) (CMV Viremia Clearance) at End of Week 8	Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration less than (<) lower limit of quantification (LLOQ) that is, <137 International Units per milliliter (IU/mL) when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive postbaseline samples, separated by at least 5 days. Percentage of participants with confirmed CMV viremia clearance at end of study Week 8 regardless of whether either study-assigned treatment was discontinued before the end of the stipulated 8 weeks of therapy, and could not have received alternative anti-CMV treatment were reported.	Week 8
Secondary	Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control at End of Week 8, Followed by Maintenance of Treatment Effect at Week 16	Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration	Up to Week 16
Secondary	Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance After Receiving 8 Weeks of Study-assigned Treatment	Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration	At Week 8 through Weeks 12, 16 and 20
Secondary	Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control After Receiving 8 Weeks of Study-assigned Treatment Through Weeks 12, 16 and 20	Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration	At Week 8 through Weeks 12, 16 and 20
Secondary	Percentage of Participants Who Maintained CMV Viremia Clearance and CMV Infection Symptom Control at the End of Study Week 8 Through Weeks 12 and 20 Regardless of Whether Either Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy	Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration	At Week 8 through Weeks 12 and 20
Secondary	Percentage of Participants With Recurrence of CMV Viremia During the First 8 Weeks of Study Regardless of Whether Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy	Recurrence of CMV viremia was 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 achieving confirmed viremia clearance, regardless of whether either study-assigned treatment was discontinued before the end of the stipulated 8 weeks of therapy. Percentage of participants with recurrence of CMV viremia during the first 8 weeks of study regardless of whether study-assigned treatment was discontinued before 8 weeks of therapy were reported.	At Week 8
Secondary	Percentage of Participants With Recurrence of CMV Viremia During the 12 Weeks Follow-up Period Regardless of Whether Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy	Recurrence of CMV viremia was defined as plasma CMV DNA concentration >=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance, regardless of whether either study-assigned treatment was discontinued before the end of the stipulated 8 weeks of therapy. Percentage of participants with recurrence of CMV viremia during the 12 weeks follow-up period regardless of whether study-assigned treatment was discontinued before 8 weeks of therapy were reported.	End of Week 8 up to Week 20 (12 weeks follow-up period)
Secondary	Percentage of Participants With Recurrence of CMV Viremia at Any Time on Study Regardless of Whether Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy	Recurrence of CMV viremia was defined as plasma CMV DNA concentration >=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance, regardless of whether either study-assigned treatment was discontinued before the end of the stipulated 8 weeks of therapy. Percentage of participants with recurrence of CMV viremia during at any time on study regardless of whether study-assigned treatment was discontinued before 8 weeks of therapy were reported.	Baseline up to Week 20
Secondary	Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the First 8 Weeks of the Treatment	Recurrence of CMV viremia was defined as plasma CMV DNA concentration >=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants with recurrence of CMV viremia during the first 8 Weeks of the treatment who completed 8 weeks of study-assigned treatment were reported.	Baseline up to Week 8
Secondary	Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the 12 Weeks of Follow-up Period	Recurrence of CMV viremia was defined as plasma CMV DNA concentration >=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants who completed 8 weeks of study-assigned treatment with recurrence of CMV viremia during the 12 weeks of follow-up period were reported.	End of Week 8 up to Week 20 (12 weeks follow-up period)
Secondary	Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the 20 Weeks of Study	Recurrence of CMV viremia was defined as plasma CMV DNA concentration >=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants with Recurrence of CMV viremia was defined as plasma CMV DNA concentration >=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants who completed 8 weeks of study-assigned treatment with recurrence of CMV viremia during the 20 weeks of study were reported.	Baseline up to Week 20
Secondary	Percentage of Participants With Recurrence of CMV Viremia While on Study-assigned Treatment	Recurrence of CMV viremia was defined as plasma CMV DNA concentration >=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants with recurrence of CMV viremia while on study-assigned treatment period were reported.	Baseline up to termination of study treatment (up to Week 8)
Secondary	Percentage of Participants With Recurrence of CMV Viremia While Off Study-assigned Treatment During Follow-up Period	Recurrence of CMV viremia was defined as plasma CMV DNA concentration >=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants with recurrence of CMV viremia while off study-assigned treatment during follow-up period were reported.	Termination of study treatment (Week 8) up to the End of the Study (Week 20)
Secondary	Number of Participants Who Had Maribavir CMV Resistance at Baseline	Resistance-associated amino acid substitutions (RASs) to maribavir are known to generally map to the pUL97 and pUL27 genes. Genotyping was performed to identify RASs mapping to the pUL97 and pUL27 genes. Number of participants who had maribavir CMV resistance at baseline were reported.	At Baseline
Secondary	Number of Participants Who Had Post-baseline Resistance to Maribavir	Resistance-associated amino acid substitutions (RASs) to maribavir are known to generally map to the pUL97 and pUL27 genes. Genotyping was performed to identify RASs mapping to the pUL97 and pUL27 genes. Number of participants who had post-baseline resistance to maribavir were reported.	After first dose of study drug up to Week 20
Secondary	Number of Participants With All-cause Mortality by the End of the Study	All-cause mortality was analyzed by the end of study regardless of the use of rescue treatment or alternative anti-CMV treatment. Number of participants who died during the entire study period were reported.	From enrollment up to end of study (approximately 44 months)
Secondary	Time to All Cause Mortality	The time to all-cause mortality by the end of the study participation in days was calculated. Participants who were alive at the last study follow-up (regardless of use of rescue or alternative anti-CMV treatment), withdrew from study or were lost to follow-up were censored at the date of last contact.	From enrollment to last serious adverse event (SAE) follow-up (approximately Week 28)
Secondary	Percentage of Participants Who Achieved Confirmed Clearance of Plasma CMV DNA (CMV Viremia Clearance) at End of Week 8 After Starting Maribavir Rescue Treatment	Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration	From start of maribavir rescue treatment through 8 weeks
Secondary	Percentage of Participants Receiving Maribavir Rescue Treatment Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control at Week 8 With Maintenance of Effect Through Week 16	Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration	Up to Week 16
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs During the On-treatment Observation Period	An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Serious AE was any untoward medical occurrence (whether considered to be related to study-assigned treatment or not) that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital abnormality/birth defect, or was an important medical event. TEAEs was defined as any adverse events (classified by preferred term) that had a start date on or after the first dose of study treatment or that had a start date before the date of first dose of study treatment, but increased in severity after the first dose of study treatment.	Baseline up to 7 days or 21 days (if cidofovir used) after the last dose of study treatment (up to Week 8)
Secondary	Predose Concentration (Cmin) of Maribavir	Cmin of maribavir was reported.	Predose at Week 1, 4 and 8
Secondary	Area Under the Concentration Time Curve Over the 12-hour Dosing Interval at Steady State (AUC0-tau) of Marivabir for Adolescent Participants	AUC0-tau of maribavir for adolescent participants was planned to be reported.	Week 1: Pre-morning dose and 1, 2, 3, 4, 6, 8 and 12 hours post morning dose, Week 4: Pre-morning dose, and Week 8: Pre-morning dose and 2-4 hour post morning dose
Secondary	Maximum Plasma Concentration (Cmax) of Maribavir for Adolescent Participants	Cmax of maribavir for adolescent participants was planned to be reported.	Week 1: Pre-morning dose and 1, 2, 3, 4, 6, 8 and 12 hours post morning dose
Secondary	Time When Maximum Concentration is Observed (Tmax) of Maribavir for Adolescent Participants	Tmax of maribavir for adolescent participants was planned to be reported.	Week 1: Pre-morning dose and 1, 2, 3, 4, 6, 8 and 12 hours post morning dose
Secondary	Apparent Oral Clearance (CL/F) of Maribavir for Adolescent Participants	Apparent oral clearance (CL/F) of maribavir for adolescent participants was planned to be reported.	Week 1: Pre-morning dose and 1, 2, 3, 4, 6, 8 and 12 hours post morning dose
Secondary	Apparent Volume of Distribution (Vz/F) of Maribavir for Adolescent Participants	Apparent volume of distribution (Vz/F) of maribavir for adolescent participants was planned to be reported.	Week 1: Pre-morning dose and 1, 2, 3, 4, 6, 8 and 12 hours post morning dose

External Links

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