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

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02931539
• Collaborator: (none)
• Enrollment: 352
• Locations: 135
• Arms: 2
• Actual Duration (Months): 43.8
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Cytomegalovirus (CMV)	Drug: Maribavir; Drug: Ganciclovir; Drug: Valganciclovir; Drug: Foscarnet; Drug: Cidofovir	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 352 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Dec 22, 2016
• Actual Primary Completion Date: Aug 17, 2020
• Actual Study Completion Date: Aug 17, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Maribavir Treatment Participants will receive 400 milligrams (mg) (2x200 mg tablets) maribavir twice daily orally (doses separated by a minimum of 8 hours) for 8 weeks.	Drug: Maribavir; Maribavir 400 milligrams (mg) (2x200 mg tablets) will be administered twice daily for 8 weeks.; Other Names: SHP620
Active Comparator: Investigator-Assigned Treatment Participants will receive anti-CMV agent best suited to treat the respective participant as per the investigator's prescribed dosing regimen for 8 weeks. Agents of choice include: ganciclovir, valganciclovir, foscarnet, or cidofovir.	Drug: Ganciclovir; Ganciclovir as per the investigator's prescribed dosing regimen will be administered for 8 weeks.; Drug: Valganciclovir; Valganciclovir as per the investigator's prescribed dosing regimen will be administered for 8 weeks.; Drug: Foscarnet; Foscarnet as per the investigator's prescribed dosing regimen will be administered for 8 weeks.; Drug: Cidofovir; Cidofovir as per the investigator's prescribed dosing regimen will be administered for 8 weeks.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Achieved Confirmed Clearance of Plasma Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) (CMV Viremia Clearance) at End of Week 8 [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.

Secondary Outcome Measures

1. 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 [Up to Week 16]

   Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration <LLOQ that is, <137 IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive postbaseline samples, separated by at least 5 days. CMV infection symptom control was defined as resolution or improvement of tissue invasive CMV disease or CMV syndrome for participants symptomatic at baseline, or maintaining no symptoms of tissue invasive CMV disease or CMV syndrome for participants asymptomatic at baseline. Percentage of participants who achieved CMV viremia clearance and CMV infection symptom control at end of Week 8 through Week 16 were reported.

2. Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance After Receiving 8 Weeks of Study-assigned Treatment [At Week 8 through Weeks 12, 16 and 20]

   Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration <LLOQ that is, <137IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive postbaseline samples, separated by at least 5 days. Percentage of participants who achieved confirmed CMV viremia clearance after receiving 8 weeks study-assigned treatment at end of Week 8, and maintained this effect through 12, 16 and 20 were reported.

3. 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 [At Week 8 through Weeks 12, 16 and 20]

   Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration <LLOQ that is, <137IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive postbaseline samples, separated by at least 5 days. CMV infection symptom control was defined as resolution or improvement of tissue invasive CMV disease or CMV syndrome for participants symptomatic at baseline, or maintaining no symptoms of tissue invasive CMV disease or CMV syndrome for participants asymptomatic at baseline. Percentage of participants who achieved confirmed CMV viremia clearance and CMV infection control after receiving 8 weeks study-assigned treatment at end of Week 8, and maintained this effect through 12, 16 and 20 were reported.

4. 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 [At Week 8 through Weeks 12 and 20]

   Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration <LLOQ that is, <137IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive postbaseline samples, separated by at least 5 days. CMV infection symptom control was defined as resolution or improvement of tissue invasive CMV disease or CMV syndrome for participants symptomatic at baseline or maintaining no symptoms of tissue invasive CMV disease or CMV syndrome for participants asymptomatic at baseline. 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 were reported.

5. 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 [At Week 8]

   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.

6. 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 [End of Week 8 up to Week 20 (12 weeks 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, 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.

7. 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 [Baseline up to Week 20]

   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.

8. Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the First 8 Weeks of the Treatment [Baseline up to Week 8]

   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.

9. Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the 12 Weeks of Follow-up Period [End of Week 8 up to Week 20 (12 weeks 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.

10. Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the 20 Weeks of Study [Baseline up to Week 20]

    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.

11. Percentage of Participants With Recurrence of CMV Viremia While on Study-assigned Treatment [Baseline up to termination of study treatment (up to Week 8)]

    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.

12. Percentage of Participants With Recurrence of CMV Viremia While Off Study-assigned Treatment During Follow-up Period [Termination of study treatment (Week 8) up to the End of the Study (Week 20)]

    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.

13. Number of Participants Who Had Maribavir CMV Resistance at Baseline [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.

14. Number of Participants Who Had Post-baseline Resistance to Maribavir [After first dose of study drug up to Week 20]

    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.

15. Number of Participants With All-cause Mortality by the End of the Study [From enrollment up to end of study (approximately 44 months)]

    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.

16. Time to All Cause Mortality [From enrollment to last serious adverse event (SAE) follow-up (approximately Week 28)]

    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.

17. Percentage of Participants Who Achieved Confirmed Clearance of Plasma CMV DNA (CMV Viremia Clearance) at End of Week 8 After Starting Maribavir Rescue Treatment [From start of maribavir rescue treatment through 8 weeks]

    Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration <LLOQ that is, <137 IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive postbaseline samples, separated by at least 5 days, regardless of whether the rescue treatment was discontinued before the end of the stipulated 8 weeks of therapy. Percentage of participants who achieved confirmed CMV viremia clearance at end of Week 8 after starting maribavir rescue treatment were reported.

18. 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 [Up to Week 16]

    Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration <LLOQ that is, <137 IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive postbaseline samples, separated by at least 5 days. CMV infection symptom control was defined as resolution or improvement of tissue invasive CMV disease or CMV syndrome for participants symptomatic at baseline, or maintaining no symptoms of tissue invasive CMV disease or CMV syndrome for participants asymptomatic at baseline. 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 were reported.

19. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs During the On-treatment Observation Period [Baseline up to 7 days or 21 days (if cidofovir used) after the last dose of study treatment (up to Week 8)]

    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.

20. Predose Concentration (Cmin) of Maribavir [Predose at Week 1, 4 and 8]

    Cmin of maribavir was reported.

21. Area Under the Concentration Time Curve Over the 12-hour Dosing Interval at Steady State (AUC0-tau) of Marivabir for Adolescent Participants [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]

    AUC0-tau of maribavir for adolescent participants was planned to be reported.

22. Maximum Plasma Concentration (Cmax) of Maribavir for Adolescent Participants [Week 1: Pre-morning dose and 1, 2, 3, 4, 6, 8 and 12 hours post morning dose]

    Cmax of maribavir for adolescent participants was planned to be reported.

23. Time When Maximum Concentration is Observed (Tmax) of Maribavir for Adolescent Participants [Week 1: Pre-morning dose and 1, 2, 3, 4, 6, 8 and 12 hours post morning dose]

    Tmax of maribavir for adolescent participants was planned to be reported.

24. Apparent Oral Clearance (CL/F) of Maribavir for Adolescent Participants [Week 1: Pre-morning dose and 1, 2, 3, 4, 6, 8 and 12 hours post morning dose]

    Apparent oral clearance (CL/F) of maribavir for adolescent participants was planned to be reported.

25. Apparent Volume of Distribution (Vz/F) of Maribavir for Adolescent Participants [Week 1: Pre-morning dose and 1, 2, 3, 4, 6, 8 and 12 hours post morning dose]

    Apparent volume of distribution (Vz/F) of maribavir for adolescent participants was planned to be reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. 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.

1. 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.

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

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

4. 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):

5. Absolute neutrophil count (ANC) >= 1000/ millimeter cube (mm^{3) (1.0 x 10}9/liter [L])

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

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

8. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294-0006
2	University of Arizona	Tucson	Arizona	United States	85724
3	City of Hope National Medical Center	Duarte	California	United States	91010
4	University of Southern California	Los Angeles	California	United States	90033
5	UCLA Medical Center	Los Angeles	California	United States	90095
6	UC Davis Medical Center	Sacramento	California	United States	95817
7	Stanford University	Stanford	California	United States	94305
8	Yale University School of Medicine	New Haven	Connecticut	United States	06520
9	AdventHealth	Orlando	Florida	United States	32804
10	Emory University Hospital	Atlanta	Georgia	United States	30322
11	Feinberg School of Medicine Northwestern University	Chicago	Illinois	United States	60611
12	Loyola University Medical Center	Maywood	Illinois	United States	60153
13	University of Chicago Medical Center	Maywood	Illinois	United States	60153
14	University of Kentucky	Lexington	Kentucky	United States	40536
15	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
16	University of Maryland	Baltimore	Maryland	United States	21201
17	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287
18	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
19	Brigham and Womens Hospital	Boston	Massachusetts	United States	02115
20	UMass Memorial Medical Center	Worcester	Massachusetts	United States	01655
21	University of Michigan	Ann Arbor	Michigan	United States	48109
22	Henry Ford Health System	Detroit	Michigan	United States	48202
23	William Beaumont Hospital	Royal Oak	Michigan	United States	48073
24	University of Minnesota	Minneapolis	Minnesota	United States	55454
25	Mayo Clinic - PPDS	Rochester	Minnesota	United States	59905
26	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-5400
27	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
28	Columbia University Medical Center	New York	New York	United States	10032
29	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
30	New York Presbyterian Hospital - Weill-Cornell	New York	New York	United States	10065
31	SUNY Upstate Medical Center	Syracuse	New York	United States	13210
32	Duke University Medical Center	Durham	North Carolina	United States	27710-4000
33	The Christ Hospital	Cincinnati	Ohio	United States	45220
34	University of Cincinnati	Cincinnati	Ohio	United States	45220
35	Cincinnati Children's Hospital Medical Center - PIN	Cincinnati	Ohio	United States	45229-3039
36	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
37	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
38	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
39	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
40	Medical University of South Carolina - PPDS	Charleston	South Carolina	United States	29425
41	St Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
42	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
43	Baylor All Saints Medical Center	Fort Worth	Texas	United States	76104
44	Baylor College of Medicine	Houston	Texas	United States	77030-2348
45	MD Anderson Cancer Center	Houston	Texas	United States	77030
46	University of Utah Health Sciences Center - PPDS	Salt Lake City	Utah	United States	84132
47	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
48	Westmead Hospital	Westmead	New South Wales	Australia	2145
49	Monash Health, Monash Medical Centre	Clayton	Victoria	Australia	3168
50	The Alfred Hospital	Melbourne	Victoria	Australia	3004
51	Royal Melbourne Hospital	Parkville	Victoria	Australia	3050
52	Sir Charles Gairdner Hospital	Nedlands	Washington	Australia	6009
53	Princess Alexandra Hospital	Brisbane		Australia	4102
54	Tiroler Landeskrankenanstalten GmbH	Innsbruck		Austria	6020
55	Allgemeines Krankenhaus der Stadt Wien	Wien		Austria	1090
56	UZ Antwerpen	Edegem	Antwerpen	Belgium	2650
57	Institut Jules Bordet	Bruxelles	Brussels	Belgium	1000
58	UZ Gent	Gent	Oost-Vlaanderen	Belgium	9000
59	UZ Leuven	Leuven	Vlaams Brabant	Belgium	3000
60	AZ Sint-Jan AV	Brugge	West-Vlaanderen	Belgium	8000
61	ZNA Stuivenberg	Antwerpen		Belgium	2060
62	UZ Brussel	Brussels		Belgium	1090
63	Hôpital Erasme	Bruxelles		Belgium	1070
64	University of Alberta	Edmonton	Alberta	Canada	T6G 2G3
65	Hamilton Health Sciences Corporation	Hamilton	Ontario	Canada	L8N 3Z5
66	St. Joseph's Healthcare Hamilton	Hamilton	Ontario	Canada	L8N 4A6
67	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
68	University Health Network	Toronto	Ontario	Canada	M5G 2N2
69	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec	Canada	H3T 1C5
70	McGill University Health Center	Montreal	Quebec	Canada	H4A 3J1
71	University Hospital Center Zagreb	Zagreb		Croatia	10000
72	Copenhagen University Hospital	København Ø	Capital	Denmark	2100
73	CHRU Brest - Hospital Cavale Blanche	Brest	Finistère	France	29609
74	Hôpital de Rangueil	Toulouse	Haute-Garonne	France	31059
75	Hopital Foch	Suresnes	Hauts-de-Seine	France	92150
76	CHRU Rennes	Rennes	Ille-et-Vilaine	France	35033
77	CHRU Bretonneau	Tours	Indre-et-Loire	France	37044
78	CHRU Nantes	Nantes	Loire-Atlantique	France	44093
79	Hôpital de La Croix Rousse	Lyon	Rhône	France	69004
80	Centre Hospitalier Lyon Sud	Pierre-bénite	Rhône	France	69495
81	Hopital Henri Mondor	Créteil	Val-de-Marne	France	94010
82	Hôpital Paul Brousse	Villejuif	Val-de-Marne	France	94800
83	CHU Amiens Hôpital Sud	AMIENS Cedex 1		France	80054
84	CHU Amiens Hôpital Sud	Amiens		France	80054
85	Hopital Gabriel Montpied	Clermont-Ferrand		France	63003
86	CHU de GRENOBLE	Grenoble		France	38043
87	CHRU Lille	Lille Cedex		France	59037
88	CHU Dupuytren	Limoges Cedex		France	87042
89	Groupement Hospitalier Edouard Herriot	Lyon		France	69437
90	Groupe Hospitalier Necker Enfants Malades	Paris		France	75015
91	Hôpital Saint Louis	Paris		France	75475
92	Hôpital Saint Antoine	Paris		France	75571
93	CHRU de Poitiers La Miletrie	Poitiers		France	86000
94	Institut de Cancerologie de la Loire	Saint-Priest en Jarez		France	42271
95	Hôpital Civil	STRASBOURG Cedex		France	67091
96	Hopital de Hautepierre	Strasbourg		France	67091
97	University Clinic Heidelberg - PPDS	Heidelberg	Baden-Württemberg	Germany	69120
98	Universitätsklinikum Erlangen	Erlangen	Bayern	Germany	91054
99	Universitätsklinikum Essen	Essen	Nordrhein-Westfalen	Germany	45122
100	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz	Rheinland-Pfalz	Germany	55101
101	Universitatsklinikum Leipzig	Leipzig	Sachsen	Germany	04103
102	Universitätsklinikum Erlangen	Erlangen		Germany	91054
103	University Clinic Heidelberg - PPDS	Heidelberg		Germany	69120
104	LMU Klinikum der Universität München	München		Germany	81377
105	Universitätsklinikum Tübingen	Tübingen		Germany	72076
106	Ospedale San Raffaele S.r.l. - PPDS	Milano	Lombardia	Italy	20132
107	Istituto Europeo Di Oncologia	Milano	Lombardia	Italy	20141
108	Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi	Ancona	Marche	Italy	60126
109	Azienda Ospedaliero Universitaria di Parma	Parma		Italy	43126
110	Azienda Ospedaliero Universitaria Pisana	Pisa		Italy	56216
111	Fondazione Policlinico Universitario A Gemelli	Roma		Italy	00168
112	Azienda Sanitaria Universitaria Integrata di Udine	Udine		Italy	12345
113	Singapore General Hospital (SGH)	Singapore		Singapore	169608
114	Hospital Universitario Germans Trias i Pujol	Badalona	Barcelona	Spain	08916
115	Hospital Universitario de Cruces	Barakaldo		Spain	48903
116	Fundacio Puigvert	Barcelona		Spain	08025
117	Hospital Universitario Vall d'Hebrón - PPDS	Barcelona		Spain	08035
118	Hospital de La Santa Creu i Sant Pau	Barcelona		Spain	08041
119	Hospital Universitario de Bellvitge	L'Hospitalet de Llobregat		Spain	08907
120	Hospital Universitario Puerta de Hierro - Majadahonda	Madrid		Spain	28222
121	Complejo Asistencial Universitario de Salamanca - H. Clinico	Salamanca		Spain	37007
122	Hospital Clinico Universitario de Valencia	Valencia		Spain	46010
123	Hospital Universitari i Politecnic La Fe de Valencia	Valencia		Spain	46026
124	Centre Hospitalier Universitaire Vaudois	Lausanne	Vaud (fr)	Switzerland	1011
125	University Hospital Coventry	Coventry	Birmingham	United Kingdom	CV2 2DX
126	Birmingham Heartlands Hospital	West Midlands	Birmingham	United Kingdom	B9 5SS
127	Beatson West of Scotland Cancer Centre - PPDS	Glasgow	Glasgow City	United Kingdom	G12 0YN
128	Imperial College Healthcare NHS Trust	London	London, City Of	United Kingdom	W12 0HS
129	Wythenshawe Hospital - PPDS	Wythenshawe	Manchester	United Kingdom	M23 9LT
130	Sheffield Childrens Hospital	Sheffield	Yorkshire	United Kingdom	S10 2TH
131	Royal Liverpool and Broadgreen University Hospitals NHS Trust	Liverpool		United Kingdom	L7 8XP
132	Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital	London		United Kingdom	NW3 2QG
133	Royal Free Hospital	London		United Kingdom	NW3 2QG
134	Manchester Royal Infirmary - PPDS	Manchester		United Kingdom	M13 9WL
135	Churchill Hospital	Oxford		United Kingdom	OX3 7LJ

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Shire

Study Documents (Full-Text)

• Study Protocol - Dec 7, 2018
• Statistical Analysis Plan - Sep 28, 2020

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT02931539
• Other Study ID Numbers: SHP620-303; 2015-004725-13
• First Posted: Oct 13, 2016
• Last Update Posted: Nov 3, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Cytomegalovirus Infections; Valganciclovir; Ganciclovir; Ganciclovir triphosphate; Cidofovir; Foscarnet; Maribavir

Study Results

Participant Flow

Recruitment Details

This study was conducted at 94 sites in North America, Europe, and Asia Pacific between 22 December 2016 (first participant first visit) and 17 August 2020 (last participant last visit).

Pre-assignment Detail

Participants with cytomegalovirus (CMV) infections were enrolled and randomized into two treatment groups: IAT (control), and Maribavir 400 mg. Participants randomized to IAT treatment arm, if met the stringent criteria for lack of improvement/worsening of CMV infection, considered eligible for entry into Maribavir rescue arm at Week 3 based on medical monitor review. As planned, combined data has been reported for IAT control group.

Arm/Group Title	Investigator-assigned Anti-CMV Treatment (IAT)	Maribavir 400 mg	Maribavir Rescue Arm
Arm/Group Description	Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Participants received maribavir 400 milligram (mg) (2*200 mg tablets), orally, twice daily for the 8 week treatment period.	Participants with clear evidence of virologic failure (not just intolerance) after a minimum of 3 weeks of therapy with IAT entered maribavir rescue arm and received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Period Title: Period 1: Treatment Phase
STARTED	117	235	0
Treated Participants	116	234	0
IAT (Ganciclovir/ Valganciclovir)	56	0	0
IAT (Foscarnet)	47	0	0
IAT (Cidofovir)	6	0	0
IAT (Foscarnet + Valganciclovir/Ganciclovir)	7	0	0
COMPLETED	58	199	0
NOT COMPLETED	59	36	0
Period Title: Period 1: Treatment Phase
STARTED	0	0	22
COMPLETED	0	0	20
NOT COMPLETED	0	0	2

Baseline Characteristics

Arm/Group Title	Investigator-assigned Anti-CMV Treatment (IAT)	Maribavir 400 mg	Total
Arm/Group Description	Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.	Total of all reporting groups
Overall Participants	117	235	352
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.5 (12.80)	53.8 (13.39)	53.0 (13.22)
Sex: Female, Male (Count of Participants)
Female	52 44.4%	87 37%	139 39.5%
Male	65 55.6%	148 63%	213 60.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 6%	14 6%	21 6%
Not Hispanic or Latino	95 81.2%	198 84.3%	293 83.2%
Unknown or Not Reported	15 12.8%	23 9.8%	38 10.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	7 6%	9 3.8%	16 4.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	18 15.4%	29 12.3%	47 13.4%
White	87 74.4%	179 76.2%	266 75.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	5 4.3%	18 7.7%	23 6.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Achieved Confirmed Clearance of Plasma Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) (CMV Viremia Clearance) at End of Week 8
Description	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.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Arm/Group Title	Investigator-assigned Anti-CMV Treatment (IAT)	Maribavir 400 mg
Arm/Group Description	Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	117	235
Number [percentage of participants]	23.9 20.4%	55.7 23.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Investigator-assigned Anti-CMV Treatment (IAT), Maribavir 400 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage of responders
	Estimated Value	32.8
	Confidence Interval	(2-Sided) 95%; 22.80 to 42.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	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
Description	Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration <LLOQ that is, <137 IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive postbaseline samples, separated by at least 5 days. CMV infection symptom control was defined as resolution or improvement of tissue invasive CMV disease or CMV syndrome for participants symptomatic at baseline, or maintaining no symptoms of tissue invasive CMV disease or CMV syndrome for participants asymptomatic at baseline. Percentage of participants who achieved CMV viremia clearance and CMV infection symptom control at end of Week 8 through Week 16 were reported.
Time Frame	Up to Week 16

Outcome Measure Data

Analysis Population Description

The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Arm/Group Title	Investigator-assigned Anti-CMV Treatment (IAT)	Maribavir 400 mg
Arm/Group Description	Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	117	235
Number [percentage of participants]	10.3 8.8%	18.7 8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Investigator-assigned Anti-CMV Treatment (IAT), Maribavir 400 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage of responders
	Estimated Value	9.5
	Confidence Interval	(2-Sided) 95%; 2.02 to 16.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance After Receiving 8 Weeks of Study-assigned Treatment
Description	Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration <LLOQ that is, <137IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive postbaseline samples, separated by at least 5 days. Percentage of participants who achieved confirmed CMV viremia clearance after receiving 8 weeks study-assigned treatment at end of Week 8, and maintained this effect through 12, 16 and 20 were reported.
Time Frame	At Week 8 through Weeks 12, 16 and 20

Outcome Measure Data

Analysis Population Description

The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Arm/Group Title	Investigator-assigned Anti-CMV Treatment (IAT)	Maribavir 400 mg
Arm/Group Description	Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	117	235
At Week 8	18.8 16.1%	54.9 23.4%
At Week 12	5.1 4.4%	22.6 9.6%
At Week 16	5.1 4.4%	18.7 8%
At Week 20	4.3 3.7%	18.3 7.8%

4. Secondary Outcome

Title	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
Description	Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration <LLOQ that is, <137IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive postbaseline samples, separated by at least 5 days. CMV infection symptom control was defined as resolution or improvement of tissue invasive CMV disease or CMV syndrome for participants symptomatic at baseline, or maintaining no symptoms of tissue invasive CMV disease or CMV syndrome for participants asymptomatic at baseline. Percentage of participants who achieved confirmed CMV viremia clearance and CMV infection control after receiving 8 weeks study-assigned treatment at end of Week 8, and maintained this effect through 12, 16 and 20 were reported.
Time Frame	At Week 8 through Weeks 12, 16 and 20

Outcome Measure Data

Analysis Population Description

The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Arm/Group Title	Investigator-assigned Anti-CMV Treatment (IAT)	Maribavir 400 mg
Arm/Group Description	Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	117	235
At Week 8	18.8 16.1%	54.9 23.4%
At Week 12	5.1 4.4%	22.6 9.6%
At Week 16	5.1 4.4%	18.7 8%
At Week 20	4.3 3.7%	18.3 7.8%

5. Secondary Outcome

Title	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
Description	Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration <LLOQ that is, <137IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive postbaseline samples, separated by at least 5 days. CMV infection symptom control was defined as resolution or improvement of tissue invasive CMV disease or CMV syndrome for participants symptomatic at baseline or maintaining no symptoms of tissue invasive CMV disease or CMV syndrome for participants asymptomatic at baseline. 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 were reported.
Time Frame	At Week 8 through Weeks 12 and 20

Outcome Measure Data

Analysis Population Description

The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Arm/Group Title	Investigator-assigned Anti-CMV Treatment (IAT)	Maribavir 400 mg
Arm/Group Description	Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	117	235
At Week 8	23.9 20.4%	55.7 23.7%
At Week 12	10.3 8.8%	22.6 9.6%
At Week 20	9.4 8%	18.3 7.8%

6. Secondary Outcome

Title	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
Description	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.
Time Frame	At Week 8

Outcome Measure Data

Analysis Population Description

The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Arm/Group Title	Investigator-assigned Anti-CMV Treatment (IAT)	Maribavir 400 mg
Arm/Group Description	Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	117	235
Number [percentage of participants]	12.3 10.5%	17.9 7.6%

7. Secondary Outcome

Title	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
Description	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.
Time Frame	End of Week 8 up to Week 20 (12 weeks follow-up period)

Outcome Measure Data

Analysis Population Description

The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Arm/Group Title	Investigator-assigned Anti-CMV Treatment (IAT)	Maribavir 400 mg
Arm/Group Description	Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	117	235
Number [percentage of participants]	21.5 18.4%	38.6 16.4%

8. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline up to Week 20

Outcome Measure Data

Analysis Population Description

The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Arm/Group Title	Investigator-assigned Anti-CMV Treatment (IAT)	Maribavir 400 mg
Arm/Group Description	Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	117	235
Number [percentage of participants]	33.8 28.9%	56.5 24%

9. Secondary Outcome

Title	Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the First 8 Weeks of the Treatment
Description	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.
Time Frame	Baseline up to Week 8

Outcome Measure Data

Analysis Population Description

The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study. Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure.

Arm/Group Title	Investigator-assigned Anti-CMV Treatment (IAT)	Maribavir 400 mg
Arm/Group Description	Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	37	183
Number [percentage of participants]	9.7 8.3%	15.2 6.5%

10. Secondary Outcome

Title	Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the 12 Weeks of Follow-up Period
Description	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.
Time Frame	End of Week 8 up to Week 20 (12 weeks follow-up period)

Outcome Measure Data

Analysis Population Description

The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study. Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure.

Arm/Group Title	Investigator-assigned Anti-CMV Treatment (IAT)	Maribavir 400 mg
Arm/Group Description	Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	37	183
Number [percentage of participants]	35.5 30.3%	40.9 17.4%

11. Secondary Outcome

Title	Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the 20 Weeks of Study
Description	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.
Time Frame	Baseline up to Week 20

Outcome Measure Data

Analysis Population Description

The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study. Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure.

Arm/Group Title	Investigator-assigned Anti-CMV Treatment (IAT)	Maribavir 400 mg
Arm/Group Description	Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	37	183
Number [percentage of participants]	45.2 38.6%	56.1 23.9%

12. Secondary Outcome

Title	Percentage of Participants With Recurrence of CMV Viremia While on Study-assigned Treatment
Description	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.
Time Frame	Baseline up to termination of study treatment (up to Week 8)

Outcome Measure Data

Analysis Population Description

The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Arm/Group Title	Investigator-assigned Anti-CMV Treatment (IAT)	Maribavir 400 mg
Arm/Group Description	Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	117	235
Number [percentage of participants]	4.6 3.9%	15.8 6.7%

13. Secondary Outcome

Title	Percentage of Participants With Recurrence of CMV Viremia While Off Study-assigned Treatment During Follow-up Period
Description	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.
Time Frame	Termination of study treatment (Week 8) up to the End of the Study (Week 20)

Outcome Measure Data

Analysis Population Description

The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Arm/Group Title	Investigator-assigned Anti-CMV Treatment (IAT)	Maribavir 400 mg
Arm/Group Description	Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	117	235
Number [percentage of participants]	29.2 25%	40.8 17.4%

14. Secondary Outcome

Title	Number of Participants Who Had Maribavir CMV Resistance at Baseline
Description	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.
Time Frame	At Baseline

Outcome Measure Data

Analysis Population Description

The combination of maribavir resistance set (MRS) and non-MRS set (MRS+non-MRS) included all participants in modified randomized set who had been randomized in the study and who had taken any dose of study-assigned treatment with evaluable CMV genotypic data at baseline with or without pre-existing known maribavir RASs in pUL97 and/or pUL27. Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure.

Arm/Group Title	Investigator-assigned Anti-CMV Treatment (IAT)	Maribavir Rescue Arm	Maribavir 400 mg
Arm/Group Description	Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Participants with clear evidence of virologic failure (not just intolerance) after a minimum of 3 weeks of therapy with IAT entered maribavir rescue arm and received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	100	17	214
RASs associated with pUL97 only	3 2.6%	1 0.4%	0 0%
RASs associated with pUL27 only	0 0%	0 0%	1 0.3%
RASs associated with pUL97 and pUL27	0 0%	0 0%	0 0%

15. Secondary Outcome

Title	Number of Participants Who Had Post-baseline Resistance to Maribavir
Description	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.
Time Frame	After first dose of study drug up to Week 20

Outcome Measure Data

Analysis Population Description

The combination of maribavir resistance set (MRS) and non-MRS set (MRS+non-MRS) included all participants in modified randomized set who had been randomized in the study and who had taken any dose of study-assigned treatment with evaluable CMV genotypic data at baseline with or without pre-existing known maribavir RASs in pUL97 and/or pUL27.

Arm/Group Title	Investigator-assigned Anti-CMV Treatment (IAT)	Maribavir Rescue Arm	Maribavir 400 mg
Arm/Group Description	Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Participants with clear evidence of virologic failure (not just intolerance) after a minimum of 3 weeks of therapy with IAT entered maribavir rescue arm and received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	100	17	214
RASs associated with pUL97 only	0 0%	4 1.7%	45 12.8%
RASs associated with pUL27 only	0 0%	0 0%	0 0%
RASs associated with pUL97 and pUL27	0 0%	0 0%	0 0%

16. Secondary Outcome

Title	Number of Participants With All-cause Mortality by the End of the Study
Description	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.
Time Frame	From enrollment up to end of study (approximately 44 months)

Outcome Measure Data

Analysis Population Description

The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Arm/Group Title	Investigator-assigned Anti-CMV Treatment (IAT)	Maribavir 400 mg
Arm/Group Description	Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	117	235
Count of Participants [Participants]	13 11.1%	27 11.5%

17. Secondary Outcome

Title	Time to All Cause Mortality
Description	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.
Time Frame	From enrollment to last serious adverse event (SAE) follow-up (approximately Week 28)

Outcome Measure Data

Analysis Population Description

The randomized set consisted of all participants who had signed informed consent and had begun some study procedures and were randomized to the study.

Arm/Group Title	Investigator-assigned Anti-CMV Treatment (IAT)	Maribavir 400 mg
Arm/Group Description	Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	117	235
Median (Full Range) [days]	73.0	55.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Investigator-assigned Anti-CMV Treatment (IAT), Maribavir 400 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.647
	Comments
	Method	Log Rank
	Comments	Two-sided p-value comparing treatment groups was calculated from the log rank test by Kaplan-Meier Method.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; 0.549 to 2.357
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stratified Cox regression model was used as transplant type and baseline plasma CMV DNA level as stratification factors.

18. Secondary Outcome

Title	Percentage of Participants Who Achieved Confirmed Clearance of Plasma CMV DNA (CMV Viremia Clearance) at End of Week 8 After Starting Maribavir Rescue Treatment
Description	Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration <LLOQ that is, <137 IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive postbaseline samples, separated by at least 5 days, regardless of whether the rescue treatment was discontinued before the end of the stipulated 8 weeks of therapy. Percentage of participants who achieved confirmed CMV viremia clearance at end of Week 8 after starting maribavir rescue treatment were reported.
Time Frame	From start of maribavir rescue treatment through 8 weeks

Outcome Measure Data

Analysis Population Description

The rescue set consisted of all participants who entered the rescue arm and received any dose of maribavir as rescue therapy. As planned, this OM was assessed only in maribavir rescue arm.

Arm/Group Title	Maribavir Rescue Arm
Arm/Group Description	Participants with clear evidence of virologic failure (not just intolerance) after a minimum of 3 weeks of therapy with IAT entered maribavir rescue arm and received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	22
Number (95% Confidence Interval) [percentage of participants]	50.0 42.7%

19. Secondary Outcome

Title	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
Description	Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration <LLOQ that is, <137 IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive postbaseline samples, separated by at least 5 days. CMV infection symptom control was defined as resolution or improvement of tissue invasive CMV disease or CMV syndrome for participants symptomatic at baseline, or maintaining no symptoms of tissue invasive CMV disease or CMV syndrome for participants asymptomatic at baseline. 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 were reported.
Time Frame	Up to Week 16

Outcome Measure Data

Analysis Population Description

The rescue set consisted of all participants who entered the rescue arm and received any dose of maribavir as rescue therapy. As planned, this OM was assessed only in maribavir rescue arm.

Arm/Group Title	Maribavir Rescue Arm
Arm/Group Description	Participants with clear evidence of virologic failure (not just intolerance) after a minimum of 3 weeks of therapy with IAT entered maribavir rescue arm and received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	22
Number (95% Confidence Interval) [percentage of participants]	27.3 23.3%

20. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs During the On-treatment Observation Period
Description	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.
Time Frame	Baseline up to 7 days or 21 days (if cidofovir used) after the last dose of study treatment (up to Week 8)

Outcome Measure Data

Analysis Population Description

The safety set consisted of all participants who had taken any dose of study treatment.

Arm/Group Title	Investigator-assigned Anti-CMV Treatment (IAT)	Maribavir Rescue Arm	Maribavir 400 mg
Arm/Group Description	Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion Participants received 1 or 2 of the 4 anti-CMV agents from the following: ganciclovir, valganciclovir, foscarnet, or cidofovir based on the investigator's discretion for the 8 week treatment period.	Participants with clear evidence of virologic failure (not just intolerance) after a minimum of 3 weeks of therapy with IAT entered maribavir rescue arm and received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	116	22	234
TEAEs	106 90.6%	22 9.4%	228 64.8%
Serious TEAEs	43 36.8%	11 4.7%	90 25.6%

21. Secondary Outcome

Title	Predose Concentration (Cmin) of Maribavir
Description	Cmin of maribavir was reported.
Time Frame	Predose at Week 1, 4 and 8

Outcome Measure Data

Analysis Population Description

The pharmacokinetic set consisted of all participants who had taken any dose of study treatment and who had plasma samples drawn and tested for maribavir concentrations. Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure and "number analyzed" were participants who were evaluable for the outcome measure at given time points.

Arm/Group Title	Maribavir 400 mg	Maribavir Rescue Arm
Arm/Group Description	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.	Participants with clear evidence of virologic failure (not just intolerance) after a minimum of 3 weeks of therapy with IAT entered maribavir rescue arm and received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	208	20
Cmin at Week 1	8.77 (7.88)	8.57 (6.28)
Cmin at Week 4	7.59 (7.05)	5.75 (3.99)
Cmin at Week 8	7.19 (6.41)	5.65 (4.47)

22. Secondary Outcome

Title	Area Under the Concentration Time Curve Over the 12-hour Dosing Interval at Steady State (AUC0-tau) of Marivabir for Adolescent Participants
Description	AUC0-tau of maribavir for adolescent participants was planned to be reported.
Time Frame	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

Outcome Measure Data

Analysis Population Description

The pharmacokinetic set consisted of all participants who had taken any dose of study treatment and who had plasma samples drawn and tested for maribavir concentrations. This OM was planned to be analyzed only in adolescent participants. Data was not collected and analyzed as adolescent participants were not enrolled in this study. Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure.

Arm/Group Title	Maribavir 400 mg	Maribavir Rescue Arm
Arm/Group Description	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.	Participants with clear evidence of virologic failure (not just intolerance) after a minimum of 3 weeks of therapy with IAT entered maribavir rescue arm and received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	0	0

23. Secondary Outcome

Title	Maximum Plasma Concentration (Cmax) of Maribavir for Adolescent Participants
Description	Cmax of maribavir for adolescent participants was planned to be reported.
Time Frame	Week 1: Pre-morning dose and 1, 2, 3, 4, 6, 8 and 12 hours post morning dose

Outcome Measure Data

Analysis Population Description

The pharmacokinetic set consisted of all participants who had taken any dose of study treatment and who had plasma samples drawn and tested for maribavir concentrations. This OM was planned to be analyzed only in adolescent participants. Data was not collected and analyzed as adolescent participants were not enrolled in this study. Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure.

Arm/Group Title	Maribavir 400 mg	Maribavir Rescue Arm
Arm/Group Description	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.	Participants with clear evidence of virologic failure (not just intolerance) after a minimum of 3 weeks of therapy with IAT entered maribavir rescue arm and received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	0	0

24. Secondary Outcome

Title	Time When Maximum Concentration is Observed (Tmax) of Maribavir for Adolescent Participants
Description	Tmax of maribavir for adolescent participants was planned to be reported.
Time Frame	Week 1: Pre-morning dose and 1, 2, 3, 4, 6, 8 and 12 hours post morning dose

Outcome Measure Data

Analysis Population Description

The pharmacokinetic set consisted of all participants who had taken any dose of study treatment and who had plasma samples drawn and tested for maribavir concentrations. This OM was planned to be analyzed only in adolescent participants. Data was not collected and analyzed as adolescent participants were not enrolled in this study. Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure.

Arm/Group Title	Maribavir 400 mg	Maribavir Rescue Arm
Arm/Group Description	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.	Participants with clear evidence of virologic failure (not just intolerance) after a minimum of 3 weeks of therapy with IAT entered maribavir rescue arm and received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	0	0

25. Secondary Outcome

Title	Apparent Oral Clearance (CL/F) of Maribavir for Adolescent Participants
Description	Apparent oral clearance (CL/F) of maribavir for adolescent participants was planned to be reported.
Time Frame	Week 1: Pre-morning dose and 1, 2, 3, 4, 6, 8 and 12 hours post morning dose

Outcome Measure Data

Analysis Population Description

The pharmacokinetic set consisted of all participants who had taken any dose of study treatment and who had plasma samples drawn and tested for maribavir concentrations. This OM was planned to be analyzed only in adolescent participants. Data was not collected and analyzed as adolescent participants were not enrolled in this study. Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure.

Arm/Group Title	Maribavir 400 mg	Maribavir Rescue Arm
Arm/Group Description	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.	Participants with clear evidence of virologic failure (not just intolerance) after a minimum of 3 weeks of therapy with IAT entered maribavir rescue arm and received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	0	0

26. Secondary Outcome

Title	Apparent Volume of Distribution (Vz/F) of Maribavir for Adolescent Participants
Description	Apparent volume of distribution (Vz/F) of maribavir for adolescent participants was planned to be reported.
Time Frame	Week 1: Pre-morning dose and 1, 2, 3, 4, 6, 8 and 12 hours post morning dose

Outcome Measure Data

Analysis Population Description

The pharmacokinetic set consisted of all participants who had taken any dose of study treatment and who had plasma samples drawn and tested for maribavir concentrations. This OM was planned to be analyzed only in adolescent participants. Data was not collected and analyzed as adolescent participants were not enrolled in this study. Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure.

Arm/Group Title	Maribavir 400 mg	Maribavir Rescue Arm
Arm/Group Description	Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.	Participants with clear evidence of virologic failure (not just intolerance) after a minimum of 3 weeks of therapy with IAT entered maribavir rescue arm and received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
Measure Participants	0	0

Adverse Events

Time Frame	Baseline up to end of study (approximately 44 months)
Arm/Group Title	IAT: Ganciclovir/ Valganciclovir		IAT: Foscarnet		IAT: Cidofovir		IAT: Foscarnet + Ganciclovir/ Valganciclovir		Maribavir 400 mg		Maribavir Rescue Arm
Arm/Group Description	Participants received ganciclovir intravenously or valganciclovir orally based on the the investigator's discretion for the 8 week treatment period.		Participants received foscarnet intravenously based on investigator's discretion for the 8 week treatment period.		Participants received cidofovir intravenously based on the investigator's discretion for the 8 week treatment period.		Participants received foscarnet intravenously in combination with ganciclovir intravenously or valganciclovir orally based on investigator's discretion for the 8 week treatment period.		Participants received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.		Participants with clear evidence of virologic failure (not just intolerance) after a minimum of 3 weeks of therapy with IAT entered maribavir rescue arm and received maribavir 400 mg (2*200 mg tablets), orally, twice daily for the 8 week treatment period.
All Cause Mortality
	IAT: Ganciclovir/ Valganciclovir		IAT: Foscarnet		IAT: Cidofovir		IAT: Foscarnet + Ganciclovir/ Valganciclovir		Maribavir 400 mg		Maribavir Rescue Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/56 (10.7%)		7/47 (14.9%)		0/6 (0%)		0/7 (0%)		27/234 (11.5%)		0/22 (0%)
Serious Adverse Events
	IAT: Ganciclovir/ Valganciclovir		IAT: Foscarnet		IAT: Cidofovir		IAT: Foscarnet + Ganciclovir/ Valganciclovir		Maribavir 400 mg		Maribavir Rescue Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/56 (58.9%)		26/47 (55.3%)		3/6 (50%)		1/7 (14.3%)		131/234 (56%)		14/22 (63.6%)
Blood and lymphatic system disorders
Anaemia	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	4/234 (1.7%)	4	2/22 (9.1%)	2
Febrile neutropenia	4/56 (7.1%)	4	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	3/234 (1.3%)	3	2/22 (9.1%)	2
Leukocytosis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Neutropenia	3/56 (5.4%)	3	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	1/22 (4.5%)	1
Pancytopenia	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Sickle cell anaemia with crisis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Thrombocytopenia	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
Thrombotic microangiopathy	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Febrile bone marrow aplasia	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Haemolytic anaemia	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Immune thrombocytopenia	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Cardiac disorders
Acute myocardial infarction	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Cardiac arrest	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Cardiac failure congestive	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	1/22 (4.5%)	1
Pericarditis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Tachycardia	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Atrial fibrillation	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Cardiac failure	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Myocardial infarction	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
Eye disorders
Glaucoma	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Iridocyclitis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	3/234 (1.3%)	5	0/22 (0%)	0
Colitis	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Diarrhoea	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	8/234 (3.4%)	8	0/22 (0%)	0
Gastrointestinal haemorrhage	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	3/234 (1.3%)	3	0/22 (0%)	0
Haematochezia	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Nausea	1/56 (1.8%)	1	2/47 (4.3%)	2	0/6 (0%)	0	0/7 (0%)	0	3/234 (1.3%)	3	0/22 (0%)	0
Pancreatitis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	2	0/22 (0%)	0
Vomiting	0/56 (0%)	0	1/47 (2.1%)	1	1/6 (16.7%)	1	0/7 (0%)	0	2/234 (0.9%)	2	1/22 (4.5%)	1
Food poisoning	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Gastrointestinal angiodysplasia	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Ileal perforation	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
General disorders
Adverse drug reaction	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Asthenia	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Disease progression	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Drug interaction	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Fatigue	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
General physical health deterioration	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
Malaise	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	3/234 (1.3%)	3	0/22 (0%)	0
Multiple organ dysfunction syndrome	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	3/234 (1.3%)	3	0/22 (0%)	0
Pyrexia	1/56 (1.8%)	1	2/47 (4.3%)	2	0/6 (0%)	0	0/7 (0%)	0	6/234 (2.6%)	6	1/22 (4.5%)	1
Treatment failure	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Oedema peripheral	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Hepatobiliary disorders
Cholecystitis	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Drug-induced liver injury	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Hepatic failure	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Biliary colic	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Cholecystitis acute	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Immune system disorders
Acute graft versus host disease	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
Graft versus host disease in gastrointestinal tract	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	3/234 (1.3%)	5	1/22 (4.5%)	1
Graft versus host disease in liver	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Transplant rejection	2/56 (3.6%)	2	1/47 (2.1%)	1	0/6 (0%)	0	1/7 (14.3%)	1	2/234 (0.9%)	2	0/22 (0%)	0
Graft versus host disease	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Renal transplant failure	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Infections and infestations
Arthritis bacterial	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Aspergillus infection	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
BK virus infection	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Bacteraemia	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	3/234 (1.3%)	3	0/22 (0%)	0
Bacterial pyelonephritis	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Bronchopulmonary aspergillosis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Cytomegalovirus chorioretinitis	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	5/234 (2.1%)	5	0/22 (0%)	0
Cytomegalovirus colitis	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	1/22 (4.5%)	1
Cytomegalovirus infection	3/56 (5.4%)	3	0/47 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	9/234 (3.8%)	9	1/22 (4.5%)	1
Cytomegalovirus infection reactivation	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	7/234 (3%)	8	0/22 (0%)	0
Cytomegalovirus mucocutaneous ulcer	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Cytomegalovirus syndrome	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	3/234 (1.3%)	3	0/22 (0%)	0
Cytomegalovirus viraemia	3/56 (5.4%)	3	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	12/234 (5.1%)	13	1/22 (4.5%)	1
Device related infection	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Device related sepsis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Encephalitis cytomegalovirus	1/56 (1.8%)	1	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	5/234 (2.1%)	6	1/22 (4.5%)	1
Encephalitis viral	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Enterococcal bacteraemia	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Erysipelas	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Escherichia bacteraemia	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
Escherichia sepsis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
Gastroenteritis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Gastroenteritis rotavirus	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
H1N1 influenza	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Herpes simplex	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Herpes zoster	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	1/22 (4.5%)	1
Herpes zoster meningoencephalitis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Infection	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Influenza	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
Osteomyelitis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Periorbital cellulitis	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Pneumonia	1/56 (1.8%)	1	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	4/234 (1.7%)	4	0/22 (0%)	0
Pneumonia cryptococcal	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Pneumonia cytomegaloviral	2/56 (3.6%)	2	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
Pneumonia haemophilus	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Pseudomonal sepsis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Pulmonary tuberculosis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Respiratory syncytial virus infection	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Respiratory tract infection	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	2	1/22 (4.5%)	1
Septic shock	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
Sinusitis	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Staphylococcal bacteraemia	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
Streptococcal bacteraemia	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Varicella zoster virus infection	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
Viral upper respiratory tract infection	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Adenovirus infection	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Atypical pneumonia	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Bacterial infection	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Campylobacter gastroenteritis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
Cellulitis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Cerebral toxoplasmosis	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Clostridium colitis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Clostridium difficile colitis	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Coronavirus infection	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Cytomegalovirus enterocolitis	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Cytomegalovirus gastroenteritis	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
Cytomegalovirus gastrointestinal infection	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Febrile infection	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Fungal skin infection	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Neutropenic sepsis	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Pneumocystis jirovecii pneumonia	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	3/234 (1.3%)	3	0/22 (0%)	0
Pneumonia fungal	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Pneumonia respiratory syncytial viral	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Respiratory tract infection viral	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Salmonellosis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Sepsis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Septic arthritis staphylococcal	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Sinusitis fungal	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Staphylococcal osteomyelitis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Stenotrophomonas infection	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Tuberculosis	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Upper respiratory tract infection	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Urinary tract infection	1/56 (1.8%)	1	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Urosepsis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Vascular device infection	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	1/22 (4.5%)	1
Pyelonephritis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	1/22 (4.5%)	2
Injury, poisoning and procedural complications
Incorrect dose administered	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Procedural pneumothorax	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Spinal fracture	0/56 (0%)	0	1/47 (2.1%)	1	1/6 (16.7%)	1	0/7 (0%)	0	0/234 (0%)	0	1/22 (4.5%)	2
Transplant dysfunction	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Skin laceration	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Transplant failure	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Wound dehiscence	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Investigations
General physical condition abnormal	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	1/22 (4.5%)	1
Haemoglobin decreased	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Hepatic enzyme increased	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Immunosuppressant drug level increased	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Viral load increased	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	1/22 (4.5%)	1
Weight decreased	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	3	0/22 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
Failure to thrive	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
Hypokalaemia	0/56 (0%)	0	1/47 (2.1%)	1	1/6 (16.7%)	1	0/7 (0%)	0	0/234 (0%)	0	1/22 (4.5%)	1
Hyponatraemia	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
Acidosis hyperchloraemic	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Diabetes mellitus inadequate control	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Hypernatraemia	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Arthritis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Intervertebral disc compression	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Rhabdomyolysis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia recurrent	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Acute myeloid leukaemia recurrent	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Leukaemia recurrent	1/56 (1.8%)	1	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
Renal cell carcinoma	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Diffuse large B-cell lymphoma recurrent	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Post transplant lymphoproliferative disorder	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Nervous system disorders
Paraesthesia	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Guillain-Barre syndrome	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Ischaemic stroke	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Syncope	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	3/234 (1.3%)	3	0/22 (0%)	0
Epilepsy	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	1/22 (4.5%)	1
Transient ischaemic attack	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	1/22 (4.5%)	1
Product Issues
Device breakage	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Psychiatric disorders
Mental status changes	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	3/234 (1.3%)	3	0/22 (0%)	0
Substance-induced psychotic disorder	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Depression	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	1/22 (4.5%)	1
Renal and urinary disorders
Acute kidney injury	0/56 (0%)	0	6/47 (12.8%)	6	0/6 (0%)	0	0/7 (0%)	0	13/234 (5.6%)	14	2/22 (9.1%)	2
Haematuria	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Nephrolithiasis	1/56 (1.8%)	1	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Renal impairment	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Nephrotic syndrome	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Renal artery stenosis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Urinary retention	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Vesicoureteric reflux	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	1/22 (4.5%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/56 (0%)	0	2/47 (4.3%)	2	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Acute respiratory failure	2/56 (3.6%)	2	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Dyspnoea	2/56 (3.6%)	2	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	3/234 (1.3%)	3	1/22 (4.5%)	1
Hypoxia	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
Pleural effusion	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	2	0/22 (0%)	0
Pneumomediastinum	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Pneumothorax	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
Pulmonary embolism	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Pulmonary mass	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Respiratory distress	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Respiratory failure	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	4/234 (1.7%)	4	0/22 (0%)	0
Pneumonia aspiration	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Pulmonary oedema	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Cough	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	1/22 (4.5%)	1
Skin and subcutaneous tissue disorders
Diabetic foot	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Vascular disorders
Deep vein thrombosis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	3/234 (1.3%)	3	1/22 (4.5%)	1
Hypertension	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Orthostatic hypotension	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Hypotension	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Venous thrombosis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Other (Not Including Serious) Adverse Events
	IAT: Ganciclovir/ Valganciclovir		IAT: Foscarnet		IAT: Cidofovir		IAT: Foscarnet + Ganciclovir/ Valganciclovir		Maribavir 400 mg		Maribavir Rescue Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/56 (96.4%)		43/47 (91.5%)		5/6 (83.3%)		7/7 (100%)		229/234 (97.9%)		22/22 (100%)
Blood and lymphatic system disorders
Anaemia	7/56 (12.5%)	8	10/47 (21.3%)	12	1/6 (16.7%)	2	1/7 (14.3%)	1	31/234 (13.2%)	36	3/22 (13.6%)	3
Leukopenia	7/56 (12.5%)	8	2/47 (4.3%)	2	0/6 (0%)	0	1/7 (14.3%)	1	12/234 (5.1%)	15	4/22 (18.2%)	4
Neutropenia	19/56 (33.9%)	41	8/47 (17%)	17	0/6 (0%)	0	1/7 (14.3%)	2	38/234 (16.2%)	92	7/22 (31.8%)	13
Thrombocytopenia	7/56 (12.5%)	8	2/47 (4.3%)	2	0/6 (0%)	0	0/7 (0%)	0	18/234 (7.7%)	19	1/22 (4.5%)	1
Lymphadenopathy	0/56 (0%)	0	0/47 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Cardiac disorders
Atrial flutter	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/234 (0%)	0	0/22 (0%)	0
Ear and labyrinth disorders
Ear congestion	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	2	0/234 (0%)	0	0/22 (0%)	0
Endocrine disorders
Adrenal insufficiency	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	1/234 (0.4%)	1	0/22 (0%)	0
Thyroiditis	0/56 (0%)	0	0/47 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Eye disorders
Cataract	2/56 (3.6%)	2	0/47 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	2/234 (0.9%)	2	0/22 (0%)	0
Chorioretinopathy	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/234 (0%)	0	0/22 (0%)	0
Dry eye	1/56 (1.8%)	1	1/47 (2.1%)	1	0/6 (0%)	0	1/7 (14.3%)	1	7/234 (3%)	8	0/22 (0%)	0
Pterygium	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/234 (0%)	0	0/22 (0%)	0
Vision blurred	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	3/7 (42.9%)	4	4/234 (1.7%)	4	0/22 (0%)	0
Periorbital oedema	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	2/7 (28.6%)	2	0/234 (0%)	0	0/22 (0%)	0
Gastrointestinal disorders
Abdominal pain	4/56 (7.1%)	4	1/47 (2.1%)	1	0/6 (0%)	0	2/7 (28.6%)	2	22/234 (9.4%)	26	1/22 (4.5%)	1
Abdominal pain upper	6/56 (10.7%)	8	1/47 (2.1%)	1	0/6 (0%)	0	1/7 (14.3%)	1	9/234 (3.8%)	9	1/22 (4.5%)	1
Constipation	7/56 (12.5%)	7	2/47 (4.3%)	3	0/6 (0%)	0	1/7 (14.3%)	2	14/234 (6%)	14	3/22 (13.6%)	4
Diarrhoea	16/56 (28.6%)	18	10/47 (21.3%)	15	1/6 (16.7%)	2	1/7 (14.3%)	4	67/234 (28.6%)	92	10/22 (45.5%)	13
Nausea	12/56 (21.4%)	17	16/47 (34%)	19	2/6 (33.3%)	2	2/7 (28.6%)	4	67/234 (28.6%)	88	5/22 (22.7%)	6
Vomiting	13/56 (23.2%)	16	9/47 (19.1%)	10	1/6 (16.7%)	1	2/7 (28.6%)	2	46/234 (19.7%)	69	2/22 (9.1%)	3
Abdominal pain lower	0/56 (0%)	0	2/47 (4.3%)	2	0/6 (0%)	0	1/7 (14.3%)	1	1/234 (0.4%)	1	0/22 (0%)	0
Dry mouth	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	1/7 (14.3%)	1	10/234 (4.3%)	11	0/22 (0%)	0
Odynophagia	0/56 (0%)	0	0/47 (0%)	0	1/6 (16.7%)	1	1/7 (14.3%)	1	1/234 (0.4%)	1	0/22 (0%)	0
Abdominal distension	1/56 (1.8%)	1	1/47 (2.1%)	2	0/6 (0%)	0	1/7 (14.3%)	1	7/234 (3%)	9	0/22 (0%)	0
Appendix disorder	0/56 (0%)	0	0/47 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
General disorders
Fatigue	10/56 (17.9%)	10	5/47 (10.6%)	5	0/6 (0%)	0	1/7 (14.3%)	1	36/234 (15.4%)	38	3/22 (13.6%)	3
Oedema peripheral	5/56 (8.9%)	7	7/47 (14.9%)	10	0/6 (0%)	0	2/7 (28.6%)	2	26/234 (11.1%)	27	3/22 (13.6%)	3
Pyrexia	12/56 (21.4%)	15	10/47 (21.3%)	11	2/6 (33.3%)	2	0/7 (0%)	0	32/234 (13.7%)	48	5/22 (22.7%)	6
Chills	1/56 (1.8%)	1	1/47 (2.1%)	1	1/6 (16.7%)	1	0/7 (0%)	0	2/234 (0.9%)	2	1/22 (4.5%)	1
Gait disturbance	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/234 (0%)	0	0/22 (0%)	0
Temperature intolerance	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/234 (0%)	0	0/22 (0%)	0
Asthenia	3/56 (5.4%)	3	3/47 (6.4%)	3	0/6 (0%)	0	0/7 (0%)	0	17/234 (7.3%)	20	0/22 (0%)	0
Device related thrombosis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/234 (0%)	0	0/22 (0%)	0
Hepatobiliary disorders
Cholelithiasis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/234 (0%)	0	0/22 (0%)	0
Cholestasis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/234 (0%)	0	0/22 (0%)	0
Immune system disorders
Graft versus host disease	1/56 (1.8%)	3	3/47 (6.4%)	3	0/6 (0%)	0	0/7 (0%)	0	2/234 (0.9%)	2	0/22 (0%)	0
Graft versus host disease in gastrointestinal tract	3/56 (5.4%)	3	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	6/234 (2.6%)	6	0/22 (0%)	0
Transplant rejection	0/56 (0%)	0	3/47 (6.4%)	3	0/6 (0%)	0	0/7 (0%)	0	8/234 (3.4%)	9	0/22 (0%)	0
Infections and infestations
Cytomegalovirus viraemia	5/56 (8.9%)	5	3/47 (6.4%)	3	0/6 (0%)	0	2/7 (28.6%)	2	32/234 (13.7%)	33	0/22 (0%)	0
BK virus infection	1/56 (1.8%)	1	2/47 (4.3%)	2	0/6 (0%)	0	1/7 (14.3%)	1	7/234 (3%)	8	0/22 (0%)	0
Conjunctivitis	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	2/234 (0.9%)	2	0/22 (0%)	0
Cytomegalovirus infection reactivation	4/56 (7.1%)	5	2/47 (4.3%)	2	0/6 (0%)	0	0/7 (0%)	0	25/234 (10.7%)	30	0/22 (0%)	0
Influenza	1/56 (1.8%)	1	0/47 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	1/234 (0.4%)	1	1/22 (4.5%)	1
Upper respiratory tract infection	4/56 (7.1%)	4	1/47 (2.1%)	1	0/6 (0%)	0	1/7 (14.3%)	1	13/234 (5.6%)	16	0/22 (0%)	0
Urinary tract infection	4/56 (7.1%)	4	4/47 (8.5%)	4	0/6 (0%)	0	0/7 (0%)	0	12/234 (5.1%)	13	0/22 (0%)	0
Cytomegalovirus infection	3/56 (5.4%)	3	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	13/234 (5.6%)	15	0/22 (0%)	0
Nasopharyngitis	2/56 (3.6%)	2	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	12/234 (5.1%)	16	0/22 (0%)	0
Oral candidiasis	3/56 (5.4%)	3	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	7/234 (3%)	8	1/22 (4.5%)	1
Oral herpes	0/56 (0%)	0	0/47 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	9/234 (3.8%)	10	0/22 (0%)	0
Pneumonia	0/56 (0%)	0	2/47 (4.3%)	2	0/6 (0%)	0	0/7 (0%)	0	12/234 (5.1%)	12	0/22 (0%)	0
Systemic bacterial infection	0/56 (0%)	0	0/47 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Varicella zoster virus infection	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	2/234 (0.9%)	6	0/22 (0%)	0
Rhinovirus infection	2/56 (3.6%)	2	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	7/234 (3%)	9	3/22 (13.6%)	3
Injury, poisoning and procedural complications
Fall	3/56 (5.4%)	4	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	9/234 (3.8%)	9	0/22 (0%)	0
Investigations
Blood creatinine increased	4/56 (7.1%)	4	4/47 (8.5%)	5	0/6 (0%)	0	1/7 (14.3%)	1	18/234 (7.7%)	19	1/22 (4.5%)	1
Immunosuppressant drug level increased	2/56 (3.6%)	2	0/47 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	21/234 (9%)	23	0/22 (0%)	0
Blood calcium decreased	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/234 (0%)	0	0/22 (0%)	0
Blood magnesium decreased	0/56 (0%)	0	1/47 (2.1%)	1	1/6 (16.7%)	1	0/7 (0%)	0	1/234 (0.4%)	1	1/22 (4.5%)	1
Blood phosphorus decreased	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	1/7 (14.3%)	1	0/234 (0%)	0	0/22 (0%)	0
Clostridium test positive	0/56 (0%)	0	1/47 (2.1%)	1	1/6 (16.7%)	1	0/7 (0%)	0	0/234 (0%)	0	1/22 (4.5%)	1
Liver function test increased	1/56 (1.8%)	1	0/47 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	1/234 (0.4%)	1	1/22 (4.5%)	1
Platelet count decreased	4/56 (7.1%)	5	1/47 (2.1%)	4	0/6 (0%)	0	0/7 (0%)	0	5/234 (2.1%)	6	1/22 (4.5%)	1
White blood cell count decreased	2/56 (3.6%)	2	0/47 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	2/234 (0.9%)	2	2/22 (9.1%)	2
Alanine aminotransferase increased	3/56 (5.4%)	3	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	7/234 (3%)	7	0/22 (0%)	0
Aspartate aminotransferase increased	3/56 (5.4%)	3	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	4/234 (1.7%)	4	0/22 (0%)	0
Blood urea increased	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	1/7 (14.3%)	1	4/234 (1.7%)	4	0/22 (0%)	0
Transaminases increased	2/56 (3.6%)	2	3/47 (6.4%)	3	0/6 (0%)	0	0/7 (0%)	0	5/234 (2.1%)	5	1/22 (4.5%)	1
Weight decreased	2/56 (3.6%)	2	1/47 (2.1%)	1	1/6 (16.7%)	1	0/7 (0%)	0	8/234 (3.4%)	12	0/22 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	7/56 (12.5%)	7	4/47 (8.5%)	4	1/6 (16.7%)	1	1/7 (14.3%)	1	23/234 (9.8%)	25	3/22 (13.6%)	3
Hypokalaemia	3/56 (5.4%)	4	8/47 (17%)	12	0/6 (0%)	0	1/7 (14.3%)	1	13/234 (5.6%)	16	2/22 (9.1%)	2
Hypomagnesaemia	5/56 (8.9%)	7	9/47 (19.1%)	10	1/6 (16.7%)	1	0/7 (0%)	0	14/234 (6%)	17	4/22 (18.2%)	4
Hypocalcaemia	2/56 (3.6%)	2	5/47 (10.6%)	5	0/6 (0%)	0	0/7 (0%)	0	0/234 (0%)	0	2/22 (9.1%)	2
Hypophosphataemia	3/56 (5.4%)	3	6/47 (12.8%)	10	0/6 (0%)	0	0/7 (0%)	0	4/234 (1.7%)	4	2/22 (9.1%)	2
Fluid overload	1/56 (1.8%)	1	1/47 (2.1%)	1	0/6 (0%)	0	1/7 (14.3%)	1	4/234 (1.7%)	4	0/22 (0%)	0
Hyperglycaemia	1/56 (1.8%)	1	1/47 (2.1%)	1	0/6 (0%)	0	1/7 (14.3%)	1	7/234 (3%)	7	0/22 (0%)	0
Hyperkalaemia	3/56 (5.4%)	3	2/47 (4.3%)	3	0/6 (0%)	0	0/7 (0%)	0	10/234 (4.3%)	11	1/22 (4.5%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	3/56 (5.4%)	3	3/47 (6.4%)	3	0/6 (0%)	0	0/7 (0%)	0	16/234 (6.8%)	17	0/22 (0%)	0
Pain in extremity	6/56 (10.7%)	6	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	8/234 (3.4%)	8	0/22 (0%)	0
Muscle spasms	1/56 (1.8%)	1	3/47 (6.4%)	3	0/6 (0%)	0	1/7 (14.3%)	1	7/234 (3%)	7	0/22 (0%)	0
Myalgia	1/56 (1.8%)	1	2/47 (4.3%)	2	0/6 (0%)	0	1/7 (14.3%)	1	3/234 (1.3%)	3	0/22 (0%)	0
Back pain	2/56 (3.6%)	2	2/47 (4.3%)	2	0/6 (0%)	0	0/7 (0%)	0	17/234 (7.3%)	22	1/22 (4.5%)	1
Osteopenia	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/234 (0%)	0	0/22 (0%)	0
Nervous system disorders
Dizziness	7/56 (12.5%)	7	2/47 (4.3%)	2	1/6 (16.7%)	1	2/7 (28.6%)	3	20/234 (8.5%)	23	1/22 (4.5%)	1
Dysgeusia	4/56 (7.1%)	4	0/47 (0%)	0	1/6 (16.7%)	1	1/7 (14.3%)	1	88/234 (37.6%)	95	1/22 (4.5%)	1
Headache	9/56 (16.1%)	11	9/47 (19.1%)	10	0/6 (0%)	0	3/7 (42.9%)	3	30/234 (12.8%)	34	2/22 (9.1%)	3
Taste disorder	0/56 (0%)	0	1/47 (2.1%)	1	0/6 (0%)	0	0/7 (0%)	0	21/234 (9%)	21	0/22 (0%)	0
Aura	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/234 (0%)	0	0/22 (0%)	0
Paraesthesia	1/56 (1.8%)	1	5/47 (10.6%)	6	0/6 (0%)	0	1/7 (14.3%)	1	6/234 (2.6%)	6	1/22 (4.5%)	1
Peroneal nerve palsy	0/56 (0%)	0	0/47 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/234 (0%)	0	1/22 (4.5%)	1
Peripheral sensory neuropathy	0/56 (0%)	0	0/47 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	2/234 (0.9%)	2	0/22 (0%)	0
Tremor	4/56 (7.1%)	4	1/47 (2.1%)	1	0/6 (0%)	0	1/7 (14.3%)	1	7/234 (3%)	7	1/22 (4.5%)	1
Psychiatric disorders
Anxiety	2/56 (3.6%)	2	1/47 (2.1%)	1	0/6 (0%)	0	1/7 (14.3%)	1	7/234 (3%)	7	1/22 (4.5%)	1
Insomnia	2/56 (3.6%)	2	3/47 (6.4%)	3	0/6 (0%)	0	0/7 (0%)	0	4/234 (1.7%)	4	1/22 (4.5%)	1
Renal and urinary disorders
Acute kidney injury	3/56 (5.4%)	3	7/47 (14.9%)	9	0/6 (0%)	0	0/7 (0%)	0	26/234 (11.1%)	33	1/22 (4.5%)	1
Dysuria	2/56 (3.6%)	2	4/47 (8.5%)	4	0/6 (0%)	0	0/7 (0%)	0	6/234 (2.6%)	7	1/22 (4.5%)	1
Micturition urgency	0/56 (0%)	0	3/47 (6.4%)	3	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	2	0/22 (0%)	0
Pollakiuria	1/56 (1.8%)	1	0/47 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	2	3/234 (1.3%)	4	0/22 (0%)	0
Proteinuria	0/56 (0%)	0	1/47 (2.1%)	1	1/6 (16.7%)	1	0/7 (0%)	0	2/234 (0.9%)	2	2/22 (9.1%)	2
Renal failure	1/56 (1.8%)	1	1/47 (2.1%)	1	1/6 (16.7%)	1	2/7 (28.6%)	2	3/234 (1.3%)	3	2/22 (9.1%)	2
Renal impairment	0/56 (0%)	0	3/47 (6.4%)	4	0/6 (0%)	0	0/7 (0%)	0	1/234 (0.4%)	1	0/22 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	7/56 (12.5%)	7	4/47 (8.5%)	4	1/6 (16.7%)	1	1/7 (14.3%)	1	22/234 (9.4%)	28	5/22 (22.7%)	5
Dyspnoea	4/56 (7.1%)	5	4/47 (8.5%)	4	0/6 (0%)	0	0/7 (0%)	0	23/234 (9.8%)	24	0/22 (0%)	0
Epistaxis	5/56 (8.9%)	5	3/47 (6.4%)	3	0/6 (0%)	0	0/7 (0%)	0	4/234 (1.7%)	6	1/22 (4.5%)	1
Nasal congestion	2/56 (3.6%)	2	1/47 (2.1%)	1	0/6 (0%)	0	1/7 (14.3%)	1	7/234 (3%)	8	0/22 (0%)	0
Tonsillar hypertrophy	0/56 (0%)	0	0/47 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Skin and subcutaneous tissue disorders
Nail disorder	0/56 (0%)	0	0/47 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/234 (0%)	0	0/22 (0%)	0
Rash erythematous	1/56 (1.8%)	1	0/47 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	3/234 (1.3%)	4	1/22 (4.5%)	1
Vascular disorders
Hypertension	2/56 (3.6%)	2	6/47 (12.8%)	7	0/6 (0%)	0	1/7 (14.3%)	1	15/234 (6.4%)	15	1/22 (4.5%)	2
Hypotension	4/56 (7.1%)	4	2/47 (4.3%)	2	1/6 (16.7%)	1	0/7 (0%)	0	11/234 (4.7%)	13	1/22 (4.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.