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
Condition: Cytomegalovirus (CMV)
MeSH terms: Cytomegalovirus Infections
Intervention: Maribavir; Ganciclovir; Valganciclovir; Foscarnet; Cidofovir
Intervention description: Maribavir 400 milligrams (mg) (2x200 mg tablets) will be administered twice daily for 8 weeks.; Ganciclovir as per the investigator's prescribed dosing regimen will be administered for 8 weeks.; Valganciclovir as per the investigator's prescribed dosing regimen will be administered for 8 weeks.; Foscarnet as per the investigator's prescribed dosing regimen will be administered for 8 weeks.; Cidofovir as per the investigator's prescribed dosing regimen will be administered for 8 weeks.
Intervention MeSH terms: Valganciclovir; Ganciclovir; Ganciclovir triphosphate; Cidofovir; Foscarnet; Maribavir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 352.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

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.
    

Eligibility 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.