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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Maribavir tablets
Anhui Provincial Hospital(The First Affiliated Hospital of USTC)
Hefei, Anhui, China
RECRUITINGXinqiao Hospital Army Medical University
Chongqing, Chongqing Municipality, China
RECRUITINGGuangzhou First People's Hospital
Guangzhou, Guangdong, China
RECRUITINGNanfang Hospital Southern Medical University
Guangzhou, Guangdong, China
RECRUITINGHenan Cancer Hospital
Zhengzhou, Henan, China
RECRUITINGUnion Hospital Tongji Medical College Huazhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGThe First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China
RECRUITINGPeking University People's Hospital
Beijing, North China, China
RECRUITINGInstitute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
Tianjin, Tianjin Municipality, China
RECRUITINGThe First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
RECRUITING...and 2 more locations
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From first dose of study drug up to Week 20
Number of Participants Who will Discontinue From the Study Drug and Study
Participants discontinuing the study drug treatment and the study will be reported.
Time frame: From first dose of study drug up to Week 20
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 (\<LLOQ), when assessed by CMV Test (Roche COBAS CMV 6800/8800) at a central specialty laboratory, in 2 consecutive postbaseline samples, separated by at least 5 days, regardless of whether either study-assigned treatment was discontinued before the end of the stipulated 8 weeks of therapy.
Time frame: 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 (\<LLOQ), when assessed by CMV Test (Roche COBAS CMV 6800/8800) at a central specialty laboratory, in 2 consecutive postbaseline samples, separated by at least 5 days, regardless of whether either study-assigned treatment was discontinued before the end of the stipulated 8 weeks of therapy. Symptom control is defined as resolution or improvement of tissue invasive CMV disease or CMV syndrome for participants symptomatic at baseline or no new symptoms of tissue invasive CMV disease or CMV syndrome for participants asymptomatic at baseline. This outcome measure will be assessed regardless of whether participants complete the stipulated 8 weeks of study-assigned treatment.
Time frame: 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 \<LLOQ, when assessed by CMV Test (Roche COBAS CMV 6800/8800) at a central specialty laboratory, in 2 consecutive postbaseline samples, separated by at least 5 days (after completion of 8 weeks therapy). Symptom control is defined as resolution or improvement of tissue invasive CMV disease or CMV syndrome for participants symptomatic at baseline or no new symptoms of tissue invasive CMV disease or CMV syndrome for participants asymptomatic at baseline.
Time frame: 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
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Confirmed CMV viremia clearance will be defined as plasma CMV DNA concentration \<LLOQ, when assessed by CMV Test (Roche COBAS CMV 6800/8800) at a central specialty laboratory, in 2 consecutive postbaseline samples, separated by at least 5 days (after completion of 8 weeks therapy). Symptom control is defined as resolution or improvement of tissue invasive CMV disease or CMV syndrome for participants symptomatic at baseline or no new symptoms of tissue invasive CMV disease or CMV syndrome for participants asymptomatic at baseline. The maintenance of treatment effect will be based on the achievement of CMV viremia clearance and symptom control at Week 8 after completion of 8 weeks therapy, followed by maintenance of this treatment effect through Weeks 12, 16 and 20.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to Week 20
Number of Participants With All-cause Mortality During the Study
All-cause mortality during the study will be reported.
Time frame: Up to Week 20
Maximum Observed Plasma Concentration (Cmax) at Steady State for Maribavir
Cmax at steady state for maribavir will be assessed.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Week 1, Day 7: Pre-dose, 0.5, 1.5, 3, 4, 6, 8 and 12 hours post-dose