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

• ClinicalTrials.gov Identifier: NCT02931539
• Recruitment Status: Completed
• First Posted: October 13, 2016
• Results First Posted: September 23, 2021
• Last Update Posted: November 3, 2021
• Sponsor: Shire
• Information provided by (Responsible Party): Takeda ( Shire )

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 (Clinical Trial)
• 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: December 22, 2016
• Actual Primary Completion Date: August 17, 2020
• Actual Study Completion Date: August 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 Name: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ 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 ]
    AUC0-tau of maribavir for adolescent participants was planned to be reported.
22. Maximum Plasma Concentration (Cmax) of Maribavir for Adolescent Participants [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. The participant must be able to provide written, personally signed, and dated informed consent to participate in the study before completing any study-related procedures. As applicable, a parent/both parents or legally authorized representative (LAR) must provide signature of informed consent and there must be documentation of assent by the participant before completing any study-related procedures.
2. The participant must be a recipient of hematopoietic stem cell or solid organ transplant.
3. The participant must have a documented CMV infection in whole blood or plasma, with a screening value of greater than or equal to (>=) 2730 international units per milliliter (IU/mL) in whole blood or >= 910 IU/mL in plasma in 2 consecutive assessments, separated by at least 1 day, as determined by local or central specialty laboratory quantitative polymerase chain reaction (qPCR) or comparable quantitative CMV DNA results. Both samples should be taken within 14 days prior to randomization with second sample obtained within 5 days prior to randomization. The same laboratory and same sample type (whole blood or plasma) must be used for these assessments.

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

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

5. The Investigator must be willing to treat the participant with at least one of the available anti-CMV drugs (ganciclovir, valganciclovir, foscarnet, or cidofovir). Note: Combination therapy with foscarnet and cidofovir is not permitted in the investigator-assigned anti-CMV treatment (IAT) arm due to the potential for serious nephrotoxicity.
6. The participant must be >= 12 years of age at the time of consent.
7. The participant must weigh >= 35 kilogram (kg).

8. The participant must have all of the following results as part of screening laboratory assessments (results from either the central laboratory or a local laboratory can be used for qualification):

   1. Absolute neutrophil count (ANC) >= 1000/ millimeter cube (mm^3) (1.0 x 10^9/liter [L])
   2. Platelet count >= 25,000/mm^3 [25 x 10^9/L],
   3. Hemoglobin >= 8 grams per deciliter (g/dL).
   4. Estimated glomerular filtration rate (eGFR) > 30 (milliliters per minute (mL/min) /1.73 square meter (m^2) as assessed by Modification of Diet in Renal Disease (MDRD) formula for participants >= 18 years of age or Schwartz formula for participants less than (<) 18 years of age.
9. The participant must have a negative serum beta-human chorionic gonadotropin (beta-HCG) pregnancy test at screening, if a female of child bearing potential. Additional urine pregnancy tests may be done per institutional requirements. Sexually active females of child bearing potential must agree to comply with any applicable contraceptive requirements of the protocol. If male, must agree to use an acceptable method of birth control, as defined in the protocol, during the study treatment administration period and for 90 days afterward if treated with maribavir, ganciclovir, valganciclovir, or cidofovir and for 180 days afterward if treated with foscarnet.
10. The participant must be able to swallow tablets, or receive tablets crushed and/or dispensed in water via nasogastric or orogastric tube.
11. The participant must be willing and have an understanding and ability to fully comply with study procedures and restrictions defined in the protocol.
12. The participant must be willing to provide necessary samples (example [e.g,] biopsy) for the diagnosis of tissue invasive CMV disease at baseline as determined by the Investigator.
13. The participant must have a life expectancy of >= 8 weeks.

Exclusion Criteria:

1. Have a current CMV infection that is considered refractory or resistant due to inadequate adherence to prior anti-CMV treatment, to the best knowledge of the Investigator.
2. Require ganciclovir, valganciclovir, foscarnet, or cidofovir administration for conditions other than CMV when study treatment is initiated (example: herpes simplex virus (HSV) coinfection requiring use of any of these agents after the randomization) or would need a coadministration with maribavir for CMV infection. NOTE: A participant who is not continuing with the same anti-CMV drug(s) (ganciclovir, valganciclovir or foscarnet) for the study treatment (if randomized to the investigator assigned anti-CMV treatment arm), must discontinue their use before the first dose of study drug. If participant is currently being treated with cidofovir and is assigned another anti-CMV therapy by the investigator, the participant must discontinue its use at least 14 days prior to randomization at Visit 2/Day 0 and the first dose of study treatment.
3. Be receiving leflunomide, letermovir, or artesunate when study treatment is initiated. NOTE: Participants receiving leflunomide must discontinue the use at least 14 days prior to randomization at Visit 2/Day 0 and the first dose of study treatment. Participants receiving letermovir must discontinue use at least 3 days prior to the first dose of study treatment. Participants receiving artesunate must discontinue the use prior to the first dose of study treatment.
4. Have severe vomiting, diarrhea, or other severe gastrointestinal illness within 24 hours prior to the first dose of study treatment that would preclude administration of oral/enteral medication.
5. Have known hypersensitivity to the active substance or to an excipient for a study treatment.
6. Have tissue invasive CMV disease with central nervous system involvement including the retina (example, CMV retinitis).
7. Have serum aspartate aminotransferase (AST) > 5 times upper limit of normal (ULN) at screening, or serum alanine aminotransferase (ALT) > 5 times ULN at screening, or total bilirubin >= 3.0 x ULN at screening (except for documented Gilbert's syndrome), by local or central lab. Participants with biopsy confirmed CMV hepatitis will not be excluded from study participation despite AST or ALT > 5 times ULN at screening.
8. Have known positive results for human immunodeficiency virus (HIV). Participants must have a confirmed negative HIV test result within 3 months of study entry or, if unavailable, be tested by a local laboratory during the screening period.
9. Require mechanical ventilation or vasopressors for hemodynamic support at the time of enrollment.
10. Be female and pregnant or breast feeding.
11. Have previously received maribavir.
12. Have received any investigational agent with known anti-CMV activity within 30 days before initiation of study treatment or investigational CMV vaccine at any time.
13. Have received any unapproved agent or device within 30 days before initiation of study treatment.
14. Have active malignancy with the exception of nonmelanoma skin cancer. Participants who have had a hematopoietic stem cell transplant (HSCT) and who experience relapse or progression of the malignancy as per investigator's opinion are not to be enrolled.
15. Be undergoing treatment for acute or chronic hepatitis C.
16. Have any clinically significant medical or surgical condition that, in the investigator's opinion, could interfere with the interpretation of study results, contraindicate the administration of the assigned study treatment, or compromise the safety or well-being of the participant.

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294-0006

United States, Arizona

University of Arizona

Tucson, Arizona, United States, 85724

United States, California

City of Hope National Medical Center

Duarte, California, United States, 91010

University of Southern California

Los Angeles, California, United States, 90033

UCLA Medical Center

Los Angeles, California, United States, 90095

UC Davis Medical Center

Sacramento, California, United States, 95817

Stanford University

Stanford, California, United States, 94305

United States, Connecticut

Yale University School of Medicine

New Haven, Connecticut, United States, 06520

United States, Florida

AdventHealth

Orlando, Florida, United States, 32804

United States, Georgia

Emory University Hospital

Atlanta, Georgia, United States, 30322

United States, Illinois

Feinberg School of Medicine Northwestern University

Chicago, Illinois, United States, 60611

Loyola University Medical Center

Maywood, Illinois, United States, 60153

University of Chicago Medical Center

Maywood, Illinois, United States, 60153

United States, Kentucky

University of Kentucky

Lexington, Kentucky, United States, 40536

United States, Louisiana

Ochsner Clinic Foundation

New Orleans, Louisiana, United States, 70121

United States, Maryland

University of Maryland

Baltimore, Maryland, United States, 21201

Johns Hopkins Hospital

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Brigham and Womens Hospital

Boston, Massachusetts, United States, 02115

UMass Memorial Medical Center

Worcester, Massachusetts, United States, 01655

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

Henry Ford Health System

Detroit, Michigan, United States, 48202

William Beaumont Hospital

Royal Oak, Michigan, United States, 48073

United States, Minnesota

University of Minnesota

Minneapolis, Minnesota, United States, 55454

Mayo Clinic - PPDS

Rochester, Minnesota, United States, 59905

United States, Nebraska

University of Nebraska Medical Center

Omaha, Nebraska, United States, 68198-5400

United States, New Jersey

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

United States, New York

Columbia University Medical Center

New York, New York, United States, 10032

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

New York Presbyterian Hospital - Weill-Cornell

New York, New York, United States, 10065

SUNY Upstate Medical Center

Syracuse, New York, United States, 13210

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710-4000

United States, Ohio

The Christ Hospital

Cincinnati, Ohio, United States, 45220

University of Cincinnati

Cincinnati, Ohio, United States, 45220

Cincinnati Children's Hospital Medical Center - PIN

Cincinnati, Ohio, United States, 45229-3039

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States, 44106

Nationwide Children's Hospital

Columbus, Ohio, United States, 43205

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States, 15213

United States, South Carolina

Medical University of South Carolina - PPDS

Charleston, South Carolina, United States, 29425

United States, Tennessee

St Jude Children's Research Hospital

Memphis, Tennessee, United States, 38105

United States, Texas

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390

Baylor All Saints Medical Center

Fort Worth, Texas, United States, 76104

Baylor College of Medicine

Houston, Texas, United States, 77030-2348

MD Anderson Cancer Center

Houston, Texas, United States, 77030

United States, Utah

University of Utah Health Sciences Center - PPDS

Salt Lake City, Utah, United States, 84132

United States, Washington

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States, 98109

Australia, New South Wales

Westmead Hospital

Westmead, New South Wales, Australia, 2145

Australia, Victoria

Monash Health, Monash Medical Centre

Clayton, Victoria, Australia, 3168

The Alfred Hospital

Melbourne, Victoria, Australia, 3004

Royal Melbourne Hospital

Parkville, Victoria, Australia, 3050

Australia, Washington

Sir Charles Gairdner Hospital

Nedlands, Washington, Australia, 6009

Australia

Princess Alexandra Hospital

Brisbane, Australia, 4102

Austria

Tiroler Landeskrankenanstalten GmbH

Innsbruck, Austria, 6020

Allgemeines Krankenhaus der Stadt Wien

Wien, Austria, 1090

Belgium

UZ Antwerpen

Edegem, Antwerpen, Belgium, 2650

Institut Jules Bordet

Bruxelles, Brussels, Belgium, 1000

UZ Gent

Gent, Oost-Vlaanderen, Belgium, 9000

UZ Leuven

Leuven, Vlaams Brabant, Belgium, 3000

AZ Sint-Jan AV

Brugge, West-Vlaanderen, Belgium, 8000

ZNA Stuivenberg

Antwerpen, Belgium, 2060

UZ Brussel

Brussels, Belgium, 1090

Hôpital Erasme

Bruxelles, Belgium, 1070

Canada, Alberta

University of Alberta

Edmonton, Alberta, Canada, T6G 2G3

Canada, Ontario

Hamilton Health Sciences Corporation

Hamilton, Ontario, Canada, L8N 3Z5

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada, L8N 4A6

Princess Margaret Hospital

Toronto, Ontario, Canada, M5G 2M9

University Health Network

Toronto, Ontario, Canada, M5G 2N2

Canada, Quebec

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, Canada, H3T 1C5

McGill University Health Center

Montreal, Quebec, Canada, H4A 3J1

Croatia

University Hospital Center Zagreb

Zagreb, Croatia, 10000

Denmark

Copenhagen University Hospital

København Ø, Capital, Denmark, 2100

France

CHRU Brest - Hospital Cavale Blanche

Brest, Finistère, France, 29609

Hôpital de Rangueil

Toulouse, Haute-Garonne, France, 31059

Hopital Foch

Suresnes, Hauts-de-Seine, France, 92150

CHRU Rennes

Rennes, Ille-et-Vilaine, France, 35033

CHRU Bretonneau

Tours, Indre-et-Loire, France, 37044

CHRU Nantes

Nantes, Loire-Atlantique, France, 44093

Hôpital de La Croix Rousse

Lyon, Rhône, France, 69004

Centre Hospitalier Lyon Sud

Pierre-bénite, Rhône, France, 69495

Hopital Henri Mondor

Créteil, Val-de-Marne, France, 94010

Hôpital Paul Brousse

Villejuif, Val-de-Marne, France, 94800

CHU Amiens Hôpital Sud

AMIENS Cedex 1, France, 80054

CHU Amiens Hôpital Sud

Amiens, France, 80054

Hopital Gabriel Montpied

Clermont-Ferrand, France, 63003

CHU de GRENOBLE

Grenoble, France, 38043

CHRU Lille

Lille Cedex, France, 59037

CHU Dupuytren

Limoges Cedex, France, 87042

Groupement Hospitalier Edouard Herriot

Lyon, France, 69437

Groupe Hospitalier Necker Enfants Malades

Paris, France, 75015

Hôpital Saint Louis

Paris, France, 75475

Hôpital Saint Antoine

Paris, France, 75571

CHRU de Poitiers La Miletrie

Poitiers, France, 86000

Institut de Cancerologie de la Loire

Saint-Priest en Jarez, France, 42271

Hôpital Civil

STRASBOURG Cedex, France, 67091

Hopital de Hautepierre

Strasbourg, France, 67091

Germany

University Clinic Heidelberg - PPDS

Heidelberg, Baden-Württemberg, Germany, 69120

Universitätsklinikum Erlangen

Erlangen, Bayern, Germany, 91054

Universitätsklinikum Essen

Essen, Nordrhein-Westfalen, Germany, 45122

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, Rheinland-Pfalz, Germany, 55101

Universitatsklinikum Leipzig

Leipzig, Sachsen, Germany, 04103

Universitätsklinikum Erlangen

Erlangen, Germany, 91054

University Clinic Heidelberg - PPDS

Heidelberg, Germany, 69120

LMU Klinikum der Universität München

München, Germany, 81377

Universitätsklinikum Tübingen

Tübingen, Germany, 72076

Italy

Ospedale San Raffaele S.r.l. - PPDS

Milano, Lombardia, Italy, 20132

Istituto Europeo Di Oncologia

Milano, Lombardia, Italy, 20141

Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi

Ancona, Marche, Italy, 60126

Azienda Ospedaliero Universitaria di Parma

Parma, Italy, 43126

Azienda Ospedaliero Universitaria Pisana

Pisa, Italy, 56216

Fondazione Policlinico Universitario A Gemelli

Roma, Italy, 00168

Azienda Sanitaria Universitaria Integrata di Udine

Udine, Italy, 12345

Singapore

Singapore General Hospital (SGH)

Singapore, Singapore, 169608

Spain

Hospital Universitario Germans Trias i Pujol

Badalona, Barcelona, Spain, 08916

Hospital Universitario de Cruces

Barakaldo, Spain, 48903

Fundacio Puigvert

Barcelona, Spain, 08025

Hospital Universitario Vall d'Hebrón - PPDS

Barcelona, Spain, 08035

Hospital de La Santa Creu i Sant Pau

Barcelona, Spain, 08041

Hospital Universitario de Bellvitge

L'Hospitalet de Llobregat, Spain, 08907

Hospital Universitario Puerta de Hierro - Majadahonda

Madrid, Spain, 28222

Complejo Asistencial Universitario de Salamanca - H. Clinico

Salamanca, Spain, 37007

Hospital Clinico Universitario de Valencia

Valencia, Spain, 46010

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, Spain, 46026

Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, Vaud (fr), Switzerland, 1011

United Kingdom

University Hospital Coventry

Coventry, Birmingham, United Kingdom, CV2 2DX

Birmingham Heartlands Hospital

West Midlands, Birmingham, United Kingdom, B9 5SS

Beatson West of Scotland Cancer Centre - PPDS

Glasgow, Glasgow City, United Kingdom, G12 0YN

Imperial College Healthcare NHS Trust

London, London, City Of, United Kingdom, W12 0HS

Wythenshawe Hospital - PPDS

Wythenshawe, Manchester, United Kingdom, M23 9LT

Sheffield Childrens Hospital

Sheffield, Yorkshire, United Kingdom, S10 2TH

Royal Liverpool and Broadgreen University Hospitals NHS Trust

Liverpool, United Kingdom, L7 8XP

Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital

London, United Kingdom, NW3 2QG

Royal Free Hospital

London, United Kingdom, NW3 2QG

Manchester Royal Infirmary - PPDS

Manchester, United Kingdom, M13 9WL

Churchill Hospital

Oxford, United Kingdom, OX3 7LJ

Sponsors and Collaborators

Shire

Investigators

• Study Director: Study Director; Shire

  Study Documents (Full-Text)

Documents provided by Takeda ( Shire ):

Study Protocol  [PDF] December 7, 2018

Statistical Analysis Plan  [PDF] September 28, 2020

More Information

Additional Information:

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Avery RK, Alain S, Alexander BD, Blumberg EA, Chemaly RF, Cordonnier C, Duarte RF, Florescu DF, Kamar N, Kumar D, Maertens J, Marty FM, Papanicolaou GA, Silveira FP, Witzke O, Wu J, Sundberg AK, Fournier M; SOLSTICE Trial Investigators. Maribavir for Refractory Cytomegalovirus Infections With or Without Resistance Post-Transplant: Results From a Phase 3 Randomized Clinical Trial. Clin Infect Dis. 2022 Sep 10;75(4):690-701. doi: 10.1093/cid/ciab988. Erratum In: Clin Infect Dis. 2023 Feb 8;76(3):560.

Del Pozo Martin Y. 47th Annual Meeting of the EBMT. Lancet Haematol. 2021 May;8(5):e317-e318. doi: 10.1016/S2352-3026(21)00104-6. Epub 2021 Mar 31. No abstract available.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT02931539
• Other Study ID Numbers: SHP620-303; 2015-004725-13 ( EudraCT Number )
• First Posted: October 13, 2016
• Results First Posted: September 23, 2021
• Last Update Posted: November 3, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• URL: https://vivli.org/ourmember/takeda/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Cytomegalovirus Infections; Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Valganciclovir; Ganciclovir; Ganciclovir triphosphate; Cidofovir; Foscarnet; Maribavir; Antiviral Agents; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Reverse Transcriptase Inhibitors