A Study of Maribavir in Japanese People With Cytomegalovirus (CMV) Infection

Study Overview
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Brief Summary
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The main aim of the study is to check if treatment with maribavir can protect Japanese people against Cytomegalovirus (CMV) infection, and to check side effect from the study treatment and how much maribavir participants can take without getting side effects from it. Japanese recipients of a hematopoietic stem cell transplant (HSCT) or solid organ transplant (SOT) will take Maribavir tablets two times a day for 8 weeks in this study. During the study, participants will visit their study clinic 18 times as a maximum.

Official Title
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A Phase 3, Open-Label, Single-Arm Study to Assess the Efficacy, Safety, and Pharmacokinetics of Maribavir for the Treatment of Cytomegalovirus (CMV) Infection in Japanese Recipients of a Hematopoietic Stem Cell Transplant (HSCT) or Solid Organ Transplant (SOT)

Conditions
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Cytomegalovirus (CMV)

Intervention / Treatment
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* Drug: Maribavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Be Japanese with Japanese nationality, >=16 years of age at the time of consent. Be a recipient of HSCT or SOT that is functioning at the time of Screening. Have a documented CMV infection with a screening value of >455 IU/mL in plasma in 2 consecutive assessments, separated by at least 1 day, as determined by a central specialty laboratory qPCR or comparable quantitative CMV DNA results. Both samples should be taken within 14 days prior to first dose of study treatment with the second sample obtained within 5 days prior to first dose of study treatment at Visit 2/Day 0. Have the current CMV infection after HSCT or SOT, either primary or reactivation, which, in the investigator's opinion, requires treatment and have any of the following. Asymptomatic participants: The subjects do not have CMV tissue-invasive disease or CMV syndrome (SOT subjects only) at Baseline, as determined by the investigator according to the criteria specified by Ljungman et al., 2017. Refractory or resistant participants: The participant must have a current CMV infection that is refractory to the most recently administered of the anti-CMV treatment agent(s). Refractory is defined as documented failure to achieve >1 log10 (common logarithm to base 10) decrease in CMV DNA level in plasma after a 14 day or longer treatment period with IV ganciclovir/oral valganciclovir, or IV foscarnet. 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): Absolute neutrophil count >=1,000/mm^3 (1.0 × 10^9/L) Platelet count >=25,000/mm^3 (25 × 10^9/L) Hemoglobin >=8 g/dL Estimated creatinine clearance >=30 mL/minute (estimated glomerular filtration rate by Modification of Diet in Renal Disease) Be able to swallow tablets. Have life expectancy of >=8 weeks. Weigh >=40 kg. Exclusion Criteria Have central nervous system (CNS) CMV tissue-invasive disease or CMV retinitis as assessed by the investigator at the time of Screening and prior to administration at Visit 2/Day 0. Be receiving valganciclovir, ganciclovir, foscarnet, or letermovir when study treatment is initiated, or anticipated to require 1 of these agents during the 8-week treatment period. NOTE: Participants receiving letermovir must discontinue 3 days prior to first dose of study treatment. Ganciclovir, valganciclovir, and foscarnet must be discontinued prior to the first dose of study treatment. Have known hypersensitivity to the active substance or to an excipient of the study treatments. Have severe vomiting, diarrhea, or other severe GI 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 Baseline. Pregnant or nursing female. Have received any investigational agent (including CMV-specific T-cells) with known anti-CMV activity within 30 days before initiation of the study treatment at any time. Have previously received maribavir. 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* ULN at Screening (except for documented Gilbert's syndrome), as analyzed by local or central laboratory. Have known (previously documented) positive results for 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 or SOT was performed), as determined by the investigator, are not to be enrolled. Be undergoing treatment for acute or chronic hepatitis C.

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Maribavir<br>Maribavir 400 milligrams (mg), tablets, orally twice a day (BID) for up to 8 weeks. | Drug: Maribavir<br>* Maribavir tablets<br>* Other names: TAK-620;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Confirmed Cytomegalovirus (CMV) Viremia Clearance (Clearance of Plasma CMV DNA) | Confirmed CMV viremia clearance will be defined as plasma CMV DNA concentration below the lower limit of quantification (LLOQ) to be determined depending on the selected central specialty laboratory, in 2 consecutive postbaseline samples, separated by at least 5 days. | Up to Week 8 | 
| Number of Participants with Serious Adverse Events (SAE) | An SAE is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria. | Up to Week 20 | 
| Number of Participants with Treatment-Emergent Adverse Events (TEAEs) | TEAEs will be defined as those with a start date on or after the first dose of study treatment, or with a start date before the date of first dose of study treatment but increasing in severity after the first dose of study treatment. An adverse event is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product. It does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a pharmaceutical product (including an investigational product for a new indication in Japan), whether or not related to the pharmaceutical product. | Up to Week 20 | 
| Number of Participants with Adverse Events Leading to Interruption with Maribavir |  | Up to Week 20 | 
| Number of Participants with Adverse Events Leading to Permanent Treatment Discontinuation with Maribavir |  | Up to Week 20 | 
| Number of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs | Vital sign assessments will include blood pressure, pulse, respiratory rate and body temperature. Any change in vital signs which will be deemed clinically significant by the investigator will be recorded as TEAEs. | Up to Week 20 | 
| Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings Reported as TEAEs | Any change in physical examination findings by the investigator will be recorded as TEAEs. | Up to Week 20 | 
| Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters Reported as TEAEs | Clinical laboratory evaluations will include biochemistry, endocrinology, hematology and urinalysis. Any change in clinical laboratory abnormalities which will be deemed clinically significant by the investigator will be recorded as TEAEs. | Up to Week 20 | 
| Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as TEAEs | 12-lead ECG will be evaluated. Any change in ECG assessments which will be deemed clinically significant by the investigator will be reported as TEAEs. | Up to Week 20 | 
| Immunosuppressant Drug Concentration Levels in Blood | Immunosuppressant drug concentration levels solely for participants receiving immunosuppressive therapy at baseline, Day 4, Week 1, 8, and 9 will be accessed. | Baseline, Day 4, Week 1, 8 and 9 | 
| Number of Participants with TEAEs of New Onset of Acute or Chronic Graft-versus-host Disease (GVHD), Graft Rejection, or Graft Loss |  | Up to Week 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Maintained CMV Viremia Clearance and CMV Infection Symptom Control Achieved at the End of Study Week 8 Through Weeks 12, 16 and 20 | Confirmed CMV viremia clearance will be defined as plasma CMV DNA concentration below the lower limit of quantification (LLOQ) to be determined depending on the selected central specialty laboratory, in 2 consecutive postbaseline samples, separated by at least 5 days. | At Week 8 through Weeks 12, 16 and 20 | 
| Time to First Confirmed CMV Viremia Clearance | Confirmed CMV viremia clearance will be defined as plasma CMV DNA concentration below the lower limit of quantification (LLOQ) to be determined depending on the selected central specialty laboratory, in 2 consecutive postbaseline samples, separated by at least 5 days. | Up to Week 20 | 
| Percentage of Participants with Recurrence of Confirmed CMV Viremia during the 12-Week Follow-up Period in Participants with Confirmed CMV Viremia Clearance at Week 8 Requiring Additional Anti-CMV Treatment | Confirmed recurrence or the confirmed CMV viremia recurrence will be defined as plasma CMV DNA concentration >=LLOQ to be determined depending on the selected central specialty laboratory in 2 consecutive plasma samples at least 5 days apart, after attaining viremia clearance. | Up to Week 20 | 
| Change from Baseline in Plasma CMV Viremia Load |  | Baseline, Up to Week 20 | 
| Percentage of Participants with Recurrences of CMV Resistance Mutations after Maribavir Treatment |  | Up to Week 20 | 
| Number of Kinds for CMV Genes Mutation Conferring Resistance to Maribavir after Maribavir Treatment |  | Up to Week 20 | 
| Percentage of Participants who Achieved Confirmed Clearance at 137 IU/mL or Less of Plasma CMV DNA (CMV Viremia Clearance) |  | Up to Week 8 | 
| Maribavir Minimum Concentration (Cmin) |  | Week 1, 4, and 8 |