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The main aim of this study is to learn how safe maribavir is in Chinese adults who have undergone hematopoietic stem cell or organ transplantation and have a cytomegalovirus (CMV) infection and how well they tolerate treatment with maribavir. Other aims are to see how effective maribavir is in treating CMV infection and getting rid of the symptoms, the recurrence rate of CMV infection after treatment with maribavir and if the treatment is required again. Researchers will also check for changes (mutations) occurring in the virus which may cause treatment with maribavir to no longer work well or to not work at all (resistance to maribavir).
The participants will be treated with maribavir for 8 weeks.
During the study, participants will visit their study clinic 18 times.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Maribavir | Experimental | Participants will receive maribavir 400 milligrams (mg), tablets, orally twice a day (BID) for up to 8 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Maribavir | Drug | Maribavir tablets |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAE), and Adverse Events of Special interest (AESIs) | 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 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. AESIs is defined as any adverse event of special interest. | From first dose of study drug up to Week 20 |
| Number of Participants With Clinically Significant Changes in Vital Signs | Vital signs will include temperature, arterial blood pressure (systolic and diastolic) and pulse. Any change in vital signs assessments which will be deemed clinically significant by the investigator will be reported. | From first dose of study drug up to Week 20 |
| Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters | Clinical laboratory parameters will include chemistry, hematology, and urinalysis. Any clinical laboratory abnormalities which will be deemed clinically significant by the investigator will be recorded. | From first dose of study drug up to Week 20 |
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 12-lead ECG will be evaluated. Any ECG assessments which will be deemed clinically significant by the investigator will be reported. | From first dose of study drug up to Week 20 |
| Number of Participants Who will Discontinue From the Study Drug and Study |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Confirmed Clearance of Plasma CMV Deoxyribose Nucleic Acid (DNA) (CMV Viremia Clearance) at Week 8 | Confirmed CMV viremia clearance is defined as plasma CMV DNA concentration below the lower limit of quantification (\ |
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Inclusion Criteria
The participant or the participant's legally acceptable representative is willing and able to understand and fully comply with study procedures and requirements, in the opinion of the investigator.
The participant/participant's legally representative has provided informed consent (that is, in writing, documented via a signed and dated informed consent form [ICF]) and any required privacy authorization prior to the initiation of any study procedures.
The participant is aged 18 years or older (ie, greater than or equal to [>=] 18 years) at the time of signing the ICF.
The participant must be of Chinese descent, defined as born in China and having Chinese parents and Chinese maternal and paternal grandparents.
The participant must be a recipient of hematopoietic stem cell or solid organ transplant.
The participant must have a documented CMV infection in whole blood or plasma, with a screening value of >=1,365 International unit per milliliter IU/mL in whole blood or >=455 IU/mL in plasma in 2 consecutive assessments, separated by at least 1 day, as determined by local laboratory quantitative polymerase chain reaction (qPCR) or comparable quantitative CMV DNA results. Both samples should be taken within 14 days prior to receiving the investigational product with second sample obtained within 5 days prior to receiving the investigational product. The same laboratory and same sample type (whole blood or plasma) must be used for these assessments.
The participant must have a current CMV infection that is refractory to the most recently administered of the 4 anti-CMV treatment agent(s) eg, intravenous (IV) ganciclovir/oral valganciclovir, IV foscarnet, or IV cidofovir. 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 the above 4 agents.
Participants who have documentation of 1 or more CMV genetic mutations associated with resistance to ganciclovir/valganciclovir, cidofovir, or foscarnet must also meet the definition of refractory CMV infection.
Have all the following results as part of screening laboratory assessments:
The participant must have life expectancy of at least 8 weeks.
The participant has a body weight of at least 35 kilogram (kg).
The female participant either be of nonchildbearing potential, or if of childbearing potential then have a negative serum human chorionic gonadotropin (hCG) or beta-hCG (β-hCG) pregnancy test at screening. Males, or nonpregnant, nonlactating female participants who are sexually active must agree to comply with the applicable contraceptive requirements of this protocol during the investigational product administration period and for 90 days after the last dose of investigational product.
The participant must be able to swallow tablets, or receive tablets crushed and/or dispersed in water via a nasogastric or orogastric tube.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Takeda Contact | Contact | +1-877-825-3327 | medinfoUS@takeda.com |
| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Anhui Provincial Hospital(The First Affiliated Hospital of USTC) | Recruiting | Hefei | Anhui | 230001 | China |
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| Label | URL |
|---|---|
| Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed. | View source |
| Click here to ask Takeda's chatbot for comprehensive and easy-to-understand information about clinical trials - even across products and indications - in your local language. | View source |
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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.
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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.
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| ID | Term |
|---|---|
| C400401 | maribavir |
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Participants discontinuing the study drug treatment and the study will be reported. |
| From first dose of study drug up to Week 20 |
| At Week 8 |
| Percentage of Participants With Achievement of CMV Viremia Clearance and CMV Infection Symptom Control at Weeks 8, 12, 16, and 20 | Confirmed CMV viremia clearance is defined as plasma CMV DNA concentration below the lower limit of quantification (\ | At Weeks 8, 12, 16 and 20 |
| Percentage of Participants With Achievement of CMV Viremia Clearance and CMV Infection Symptom Control at Week 8 (After Completion of 8 Weeks Therapy) | Confirmed CMV viremia clearance will be defined as plasma CMV DNA concentration \ | At Week 8 |
| Percentage of Participants With Achievement of CMV Viremia Clearance and CMV Infection Symptom Control After Completion of 8 weeks Therapy Followed by Maintenance of This Treatment Effect Through Weeks 12, 16 and 20 | Confirmed CMV viremia clearance will be defined as plasma CMV DNA concentration \ | At Weeks 12, 16 and 20 |
| Percentage of Participants With Recurrence of CMV Viremia During the First 8 Weeks and Through Week 12 to Week 20 | Recurrence of CMV viremia is defined as plasma CMV DNA concentrations greater than or equal to (>=) LLOQ, when assessed by central specialty laboratory, in 2 consecutive plasma samples separated by at least 5 days after achieving confirmed viremia clearance. | From first dose of study drug up to Week 8, and through Week 12 to Week 20 |
| Percentage of Participants With Recurrence of CMV Viremia During on Treatment and off Treatment | Recurrence of CMV viremia is defined as plasma CMV DNA concentrations >= LLOQ, when assessed by central specialty laboratory, in 2 consecutive plasma samples separated by at least 5 days after achieving confirmed viremia clearance. On treatment is the period over which participant received actual dosing (that can be before the stipulated 8 weeks of study-assigned treatment). Off treatment is the period after study treatment. | From first dose of study drug up to Week 8 (on treatment) and Week 20 (off treatment) |
| Percentage of Participants With Recurrence of CMV Viremia Requiring Alternative Treatment After Achieving CMV Viremia Clearance at Study Week 8 | Recurrence of CMV viremia is defined as plasma CMV DNA concentrations >=LLOQ, when assessed by central specialty laboratory, in 2 consecutive plasma samples separated by at least 5 days after achieving confirmed viremia clearance. | At Week 8 |
| Percentage of Participants With Mutations in the CMV Genes Conferring Resistance to Maribavir | Percentage of participants with mutations in the CMV genes conferring resistance to maribavir will be reported. | Up to Week 20 |
| Number of Participants With All-cause Mortality During the Study | All-cause mortality during the study will be reported. | Up to Week 20 |
| Maximum Observed Plasma Concentration (Cmax) at Steady State for Maribavir | Cmax at steady state for maribavir will be assessed. | Week 1, Day 7: Pre-dose, 0.5, 1.5, 3, 4, 6, 8, and 12 hours post-dose |
| Time to Reach Cmax (Tmax) at Steady State for Maribavir | Tmax at steady state of maribavir will be assessed. | Week 1, Day 7: Pre-dose, 0.5, 1.5, 3, 4, 6, 8 and 12 hours post-dose |
| Minimum Observed Plasma Concentration (Cmin) for Maribavir | Cmin of maribavir will be assessed. | Pre-dose and at Weeks 1, 4, and 8 |
| Area Under the Plasma Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration Area (AUC0-t) at Steady State for Maribavir | AUC0-t at steady state for maribavir will be assessed. | Week 1, Day 7: Pre-dose, 0.5, 1.5, 3, 4, 6, 8 and 12 hours post-dose |
| Area Under the Plasma Concentration-Time Curve Over 1 Dosing Interval of 12 Hours (AUC0-tau) at Steady State for Maribavir | AUC0-tau at steady state for maribavir will be assessed. | Week 1, Day 7: Pre-dose, 0.5, 1.5, 3, 4, 6, 8 and 12 hours post-dose |
| Half -life (t1/2) at Steady State for Maribavir | t1/2 at steady state for maribavir will be assessed. | Week 1, Day 7: Pre-dose, 0.5, 1.5, 3, 4, 6, 8 and 12 hours post-dose |
| Terminal Elimination Rate Constant (Lambda z) at Steady State for Maribavir | Lambda z at steady state for maribavir will be assessed. | Week 1, Day 7: Pre-dose, 0.5, 1.5, 3, 4, 6, 8 and 12 hours post-dose |
| Apparent Volume of Distribution (Vz/F) at Steady State for Maribavir | Vz/F at steady state for maribavir will be assessed. | Week 1, Day 7: Pre-dose, 0.5, 1.5, 3, 4, 6, 8 and 12 hours post-dose |
| Apparent Oral Clearance (CL/F) at Steady State for Maribavir | CL/F at steady state for maribavir will be assessed. | Week 1, Day 7: Pre-dose, 0.5, 1.5, 3, 4, 6, 8 and 12 hours post-dose |
| Xinqiao Hospital Army Medical University | Recruiting | Chongqing | Chongqing Municipality | 400037 | China |
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| Guangzhou First People's Hospital | Recruiting | Guangzhou | Guangdong | 510180 | China |
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| Nanfang Hospital Southern Medical University | Recruiting | Guangzhou | Guangdong | 510515 | China |
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| Henan Cancer Hospital | Recruiting | Zhengzhou | Henan | 450004 | China |
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| Union Hospital Tongji Medical College Huazhong University of Science and Technology | Recruiting | Wuhan | Hubei | 430022 | China |
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| The First Affiliated Hospital of Soochow University | Recruiting | Suzhou | Jiangsu | 215006 | China |
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| Peking University People's Hospital | Recruiting | Beijing | North China | 100044 | China |
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| Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences | Recruiting | Tianjin | Tianjin Municipality | 300020 | China |
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| The First Affiliated Hospital, Zhejiang University School of Medicine | Recruiting | Hangzhou | Zhejiang | 310003 | China |
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| The First Affiliated Hospital, Zhejiang University School of Medicine | Recruiting | Hangzhou | Zhejiang | 310003 | China |
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| The Second Affiliated Hospital, Zhejiang University School of Medicine | Recruiting | Hangzhou | Zhejiang | 310052 | China |
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