A Study of Maribavir Compared to Valganciclovir to Treat Cytomegalovirus Infections in People Who Have Received Stem Cell Transplants
Condition: Cytomegalovirus (CMV)
MeSH terms: Cytomegalovirus Infections
Intervention: Maribavir; Valganciclovir; Placebo
Intervention description: Participants will receive 400 mg of maribavir BID orally.; Participants will receive valganciclovir tablets orally.; Participants will receive placebo tablets matched to either maribavir or valganciclovir.
Intervention MeSH terms: Valganciclovir; Maribavir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 553.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No

Summary:

      This study is about treatment options for cytomegalovirus infections in people who have
      received stem cell transplants. The main aim of the study is to check if the cytomegalovirus
      infection can no longer be detected after treatment with marivabir or valganciclovir.

      Participants will take 2 tablets of marivabir or valganciclovir and 2 tablets of placebo
      twice a day for 8 weeks. A placebo will look like marivabir or valganciclovir but will not
      have any medicine in it.

      After treatment, each participant will be followed up for up to 12 weeks.

      Participants will visit their study clinic up to 18 times during the study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Be able to provide written, personally signed, and dated informed consent to
             participate in the study before completing any study-related procedures. As
             applicable, a parent/both parents or legally authorized representative (LAR) must
             provide signature of informed consent and there must be documentation of assent by the
             participants before completing any study-related procedures. During the COVID-19
             public health emergency, informed consent from a potential or current trial
             participant may, if permitted by local laws and regulations, be obtained via
             electronic informed consent (eIC) capabilities or an electronic face-to-face consent
             interview when these individuals are unable to travel to the site (FDA COVID-19
             Guidance, 27 January 2021, Q11).

          -  Be greater than or equal to (>=) 16 years of age at the time of consent.

          -  Be a recipient of hematopoietic stem cell transplant.

          -  Have a documented asymptomatic CMV infection, with a screening value of CMV DNA >=1365
             International Units per millilitre (IU/mL) to less than or equal to (<=) 273000 IU/mL
             in whole blood or >=455 IU/mL to <=91000 IU/mL in plasma in 2 consecutive assessments,
             separated by at least 1 day, as determined by local or central specialty laboratory
             quantitative polymerase chain reaction (qPCR) or comparable quantitative CMV DNA
             results. Both samples should be taken within 14 days prior to randomization with
             second sample obtained within 5 days prior to randomization. Same laboratory and same
             sample type (whole blood or plasma) should be used for these assessments. Asymptomatic
             CMV infection is defined as an infection that does not present with tissue invasive
             CMV disease, as assessed by the investigator. Participants with CMV DNA less than (<)
             910 and >=455 IU/mL in plasma or <2730 and >=1365 IU/mL in whole blood will also need
             to meet at least 1 of the following criteria for high-risk CMV infection to be
             eligible:

               1. Human leukocyte antigen (HLA)-related (sibling) donor with at least 1 mismatch at
                  1 of the following 3 HLA-gene loci: HLA-A, -B or -DR,

               2. Haploidentical donor

               3. Unrelated donor with at least 1 mismatch at 1 of the following 4 HLA -gene loci:
                  HLA-A, -B, -C and -DRB1,

               4. Use of umbilical cord blood as stem cell source,

               5. Use of ex vivo T-cell-depleted grafts,

               6. Grade 2 or greater graft-versus-host-disease (GVHD), requiring the use of
                  systemic corticosteroids (defined as the use of >=1 milligram per kilogram per
                  day (mg/kg/day) of prednisone or equivalent dose of another corticosteroid).

          -  Have the current CMV infection as the first episode of CMV viremia after HSCT, either
             primary or reactivation, which in the investigator's opinion requires treatment.

          -  Per investigator's judgment, be eligible for treatment with valganciclovir.

          -  Have all of the following results as part of screening laboratory assessments (results
             from either the central laboratory or a local laboratory can be used for
             qualification):

               1. Absolute neutrophil count to >=1000 per cubic millimeter (/mm^3) [1.0*10^9/L].

               2. Platelet count >=25,000/mm^3 [25*10^9/L].

               3. Hemoglobin >=8 grams per deciliter (g/dL).

               4. Estimated creatinine clearance >=30 milliliters per minute (mL/min).

          -  Have a negative serum beta human chorionic gonadotropin (beta-HCG) pregnancy test at
             screening, if a female of child bearing potential. Urine pregnancy tests may be done
             per institutional requirements; however they are not sufficient for eligibility
             determination. Sexually active females of child bearing potential must agree to comply
             with any applicable contraceptive requirements of the protocol. If male, must agree to
             use an acceptable method of birth control, as defined in the protocol, during the
             study treatment administration period and for 90 days afterward the last dose of study
             treatment.

          -  Be able to swallow tablets.

          -  Have life expectancy of >=8 weeks.

          -  Weigh >=40 kilograms (kg).

          -  Be willing and have an understanding and ability to fully comply with study procedures
             and restrictions defined in the protocol.

        Exclusion Criteria:

          -  Have CMV tissue invasive disease as assessed by the investigator at the time of
             screening and randomization at Visit 2/Day 0.

          -  Have a CMV infection that is known to be genotypically resistant to ganciclovir,
             valganciclovir, foscarnet, or cidofovir based on documented evidence.

          -  Be presenting with recurrent CMV infection (defined as a new detection of CMV
             infection in a participants who had at least one previously documented episode of CMV
             infection post-transplant, and who has had at least 2 weeks of undetectable CMV DNA
             between the episodes during active surveillance, based on same local laboratory and
             same sample type). The Participants must also have been off any anti-CMV treatment
             between the current and prior infection. Otherwise, the current infection may be
             considered continuation of the prior infection.

          -  Require ganciclovir, valganciclovir, foscarnet, or cidofovir administration for
             conditions other than CMV when study treatment is initiated (example: herpes simplex
             virus [HSV] co-infection requiring use of any of these agents after the randomization)
             or would need a co-administration with maribavir for CMV infection.

          -  Be receiving leflunomide, letermovir, or artesunate when study treatment is initiated.

        Note: Participants who may be receiving leflunomide must discontinue the use at least 14
        days prior to randomization at Visit 2/Day 0 and the first dose of study treatment.
        Participants receiving letermovir must discontinue use 3 days prior to first dose of study
        treatment. Participants receiving artesunate must discontinue the use prior to the first
        dose of study treatment.

          -  Be on treatment with anti-CMV agents (ganciclovir, valganciclovir, foscarnet or
             letermovir) for the current CMV infection for longer than 72 hours.

          -  Have known hypersensitivity to the active substance or to an excipient of the study
             treatments.

          -  Have severe vomiting, diarrhea, or other severe gastrointestinal illness within 24
             hours prior to the first dose of study treatment that would preclude administration of
             oral medication.

          -  Require mechanical ventilation or vasopressors for hemodynamic support at the time of
             randomization.

          -  Be female and pregnant or nursing.

          -  Have previously completed, discontinued, or have been withdrawn from this study.

          -  Have received any investigational agent with known anti-CMV activity within 30 days
             before initiation of study treatment or CMV vaccine at any time.

          -  Have received any unapproved agent or device within 30 days before initiation of study
             treatment.

          -  Have any clinically significant medical or surgical condition that, in the
             investigator's opinion, could interfere with interpretation of study results,
             contraindicate the administration of the assigned study treatment, or compromise the
             safety or well-being of the participant.

          -  Have previously received maribavir.

          -  Have serum aspartate aminotransferase (AST) greater than (>) 5 times upper limit of
             normal (ULN) at screening, or serum alanine aminotransferase (ALT) >5 times ULN at
             screening, or total bilirubin >= 3.0*ULN at screening (except for documented Gilbert's
             syndrome), as analyzed by local or central laboratory.

          -  Have known (previously documented) positive results for human immunodeficiency virus
             (HIV). Participants must have a confirmed negative HIV test result within 3 months of
             study entry or, if unavailable, be tested by a local laboratory during the screening
             period.

          -  Have active malignancy with the exception of nonmelanoma skin cancer, as determined by
             the investigator. Participants who experience relapse or progression of their
             underlying malignancy (for which HSCT was performed), as determined by the
             investigator, are not to be enrolled.

          -  Be undergoing treatment for acute or chronic hepatitis C