A Study of Maribavir Compared to Valganciclovir to Treat Cytomegalovirus Infections in People Who Have Received Stem Cell Transplants
Subjects are being invited to take part in a research study for an investigational drug called maribavir. They are being asked to participate because they had a hematopoetic stem cell transplant and were diagnosed with a cytomegalovirus (CMV) infection that has been treated for less than 72 hours with any anti-CMV medication. The word “investigational” means that a medicine is being tested and is not approved by a regulatory agency outside the use in clinical studies. In this study maribavir will be compared to valganciclovir, a drug that is commonly used to treat CMV infections. Cytomegalovirus (CMV) is a common virus, and the majority of people at some time in their life may become infected with CMV; they remain infected but do not know they have it because in healthy people it does not cause any symptoms or issues. Patients with weak defense system (a system that protects you from infections) such as patients after transplantation may be more at risk for being infected with the virus or of the virus becoming active (causing actual infection that may or may not have symptoms or could involve infection of certain body organs). When CMV infection becomes active, the virus can be found in the blood. Even with use of medicines to prevent CMV, a CMV infection can still occur or become active. The purpose of this study is to help answer the following question(s): • How does maribavir compare to valganciclovir for treatment of CMV infection? • How safe is maribavir? What unwanted effects on health might be related to the use of maribavir? • Can maribavir help subjects with CMV infection? Participants will be in the study approximately 22 weeks. Approximately 550 subjects, age 16 years or older participating at approximately 105 medical centers in about 28 countries are expected to take part in this study. As of December 2014 approximately 1,262 subjects have received maribavir in clinical studies.
Adult hematopoietic stem cell transplant recipients who have been diagnosed with a cytomegalovirus (CMV) Infection. For more information about the eligibility criteria for this trial, refer to the Health Professional version.
- 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
- 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,
- Haploidentical donor
- Unrelated donor with at least 1 mismatch at 1 of the following 4 HLA -gene loci: HLA-A, -B, -C and -DRB1,
- Use of umbilical cord blood as stem cell source,
- Use of ex vivo T-cell-depleted grafts,
- 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
- Absolute neutrophil count to >=1000 per cubic millimeter (/mm^3) [1.0*10^9/L].
- Platelet count >=25,000/mm^3 [25*10^9/L].
- Hemoglobin >=8 grams per deciliter (g/dL).
- 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.
- 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