Cytomegalovirus (CMV)
Conditions
Brief summary
The main aim of the study is to check if maribavir can treat Japanese people with 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.
Interventions
DRUGMaribavir
Maribavir tablets
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Be Japanese with Japanese nationality, \>=16 years of age at the time of consent. 2. Be a recipient of HSCT or SOT that is functioning at the time of Screening. 3. 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. 4. 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. 1. 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. 2. 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. 5. 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 \>=1,000/mm\^3 (1.0 × 10\^9/L) 2. Platelet count \>=25,000/mm\^3 (25 × 10\^9/L) 3. Hemoglobin \>=8 g/dL 4. Estimated creatinine clearance \>=30 mL/minute (estimated glomerular filtration rate by Modification of Diet in Renal Disease) 6. Be able to swallow tablets. 7. Have life expectancy of \>=8 weeks. 8. Weigh \>=40 kg.
Exclusion criteria
1. 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. 2. 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. 3. Have known hypersensitivity to the active substance or to an excipient of the study treatments. 4. 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. 5. Require mechanical ventilation or vasopressors for hemodynamic support at the time of Baseline. 6. Pregnant or nursing female. 7. 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. 8. Have previously received maribavir. 9. 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. 10. 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. 11. 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. 12. Be undergoing treatment for acute or chronic hepatitis C.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With TEAEs of New Onset of Acute or Chronic Graft-versus-host Disease (GVHD), Graft Rejection, or Graft Loss | From first dose of study drug up to Week 20 | New onset of acute or chronic GVHD assessed as TEAEs, and graft rejection, or graft loss assessed were reported. |
| Percentage of Participants Who Achieved Confirmed Clearance of Plasma CMV Deoxyribose Nucleic Acid (DNA) at Week 8 | At Week 8 | The confirmed viremia clearance was defined as a plasma CMV DNA concentration below the lower limit of quantification (LLOQ) (that is \[i.e.\], less than \[\<\] 34.5 international units per milliliter \[IU/mL\]) when assessed by the COBAS® 8800/COBAS® CMV Test, in two consecutive post-baseline samples, separated by at least 5 days. To be considered a responder for the primary endpoint, the participant must have received exclusively study-assigned treatment (regardless of whether study-assigned treatment was completed). |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | From first dose of study drug up to Week 20 | A TEAEs was defined as any event emerging or manifesting at or after the initiation of treatment with an investigational product or medicinal product or any existing event that worsened in either intensity or frequency following exposure to the investigational product or medicinal product. An SAE was any untoward medical occurrence or effect that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability / incapacity, was a congenital anomaly / birth defect or was medically important due to other reasons than the above mentioned criteria. |
| Number of Participants With TEAEs Leading to Treatment Discontinuation With Maribavir | From first dose of study drug up to Week 20 | The number of participants with TEAEs leading to maribavir study treatment discontinuation (including treatment interruption or withdrawal) were reported. |
| Number of Participants With Clinically Meaningful Changes in Vital Signs | From first dose of study drug up to Week 20 | Vital sign assessments included blood pressure, pulse, respiratory rate and body temperature. Any clinically meaningful change in vital signs which were deemed clinically significant by the investigator were reported. |
| Number of Participants With Clinically Meaningful Abnormalities in Physical Examination Findings | From first dose of study drug up to Week 20 | Physical examination included assessments of the head, eyes, ears, nose, throat, neck, lymph nodes, and the cardiovascular, dermatological, musculoskeletal, respiratory, gastrointestinal, genitourinary, and neurological systems. Any clinically meaningful change in physical examination which were deemed clinically significant by the investigator were reported. |
| Number of Participants With Clinically Meaningful Abnormalities in Clinical Laboratory Parameters | From first dose of study drug up to Week 20 | Clinical laboratory parameters included evaluations of hematology, chemistry, urinalysis. Any clinically meaningful change in clinical laboratory parameters which were deemed clinically significant by the investigator were reported. |
| Number of Participants With Clinically Meaningful Changes in Electrocardiograms (ECGs) | From first dose of study drug up to Week 20 | 12-lead ECG were evaluated. Any change in ECG assessments which are deemed clinically meaningful by the investigator were reported. |
| Number of Participants With Events of Immunosuppressant Drug Level Increased in Blood | From first dose of study drug up to Week 8 | Immunosuppressant drug concentration testing was solely for participants who received immunosuppressive therapy with tacrolimus, cyclosporine, or everolimus. The number of participants with an increased level of at least one immunosuppressant drug was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Confirmed CMV Viremia Clearance | From first dose of study drug up to Week 20 | Time to first confirmed viremia clearance was defined as time from the start date of first dose of study treatment to the date of confirmed viremia clearance (event), or the date of last CMV DNA assessment on study before the initiation of alternative anti-CMV treatment (censored). The time to first confirmed CMV viremia clearance was calculated as date of first confirmed CMV viremia clearance - randomization date + 1). The date of first confirmed CMV viremia clearance was the date of first of two consecutive samples with plasma CMV DNA \<LLOQ that meet the criteria of confirmed CMV viremia clearance. |
| Percentage of Participants With Recurrence of Confirmed CMV Viremia During Follow-up Period in Participants With Confirmed Viremia Clearance at Week 8 Who Required Additional Anti-CMV Treatment | From Week 9 up to Week 20 | Recurrence of confirmed CMV viremia was defined as plasma CMV DNA concentration greater than or equal to (\>= 34.5 IU/mL) LLOQ when assessed by the COBAS® 8800/COBAS®CMV Test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. |
| Change From Baseline in Plasma CMV Viremia Load | Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 14, 16, 18 and 20 | The change from baseline in plasma CMV viral load, i.e., plasma CMV DNA concentration was assessed and reported. |
| Percentage of Participants With Recurrence of CMV Viremia During Study Treatment and in the Follow-Up Period After the Participants Are Discontinued From Study Treatment and While On/Off Study Assigned Treatment | Study treatment: Week 0 to Week 8; Follow-up Period:Week 9 to Week 20; At Any time during study:Week 0 to Week 20; While on study assigned treatment: Week 0 to EOT(Week 8 or earlier); While off study assigned treatment: EOT (Week 8 or earlier) to Week 20 | Recurrence of CMV viremia was defined as plasma CMV DNA concentration \>= lower limit of quantification (LLOQ, i.e. \>=34.5 IU/mL) when assessed by COBAS® 8800/COBAS® CMV Test in 2 consecutive plasma samples at least 5 days apart, after being unquantifiable (\<LLOQ, i.e. \<34.5 IU/mL) for at least 5 days in 2 consecutive samples during the first 8 weeks of the study. Study Treatment: The first stipulated 8 weeks treatment. Follow up period: period started after completion of stipulated 8 weeks treatment to Week 20. While on study assigned treatment: period over which participants received actual dosing regardless of stipulated 8 weeks completion (Week 8 or earlier). While off study assigned treatment: period after study treatment, regardless of stipulated 8 weeks completion (Week 8 or earlier up to Week 20). |
| Percentage of Participants With Any Mutations in the CMV Genes Conferring Resistance to Maribavir | From first dose of study drug up to Week 20 | Plasma samples were obtained and tested to identify mutations in the viral UL97 and UL54 genes confer resistance to maribavir. Percentage of participants with any mutations in the CMV genes conferring resistance to maribavir was reported. |
| Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance at Week 8 to be Less Than (<) 137 IU/mL | At Week 8 | The confirmed CMV viremia clearance at Week 8 was defined as plasma CMV DNA concentrations \<137 IU/mL, in 2 consecutive post-baseline samples separated by at least 5 days, regardless of whether study treatment was discontinued before the end of the stipulated 8 weeks of therapy. |
| Minimum Observed Plasma Concentration (Cmin) of Maribavir | At Weeks 1, 4, and 8: Pre-dose | Cmin (pre-dose) of maribavir was assessed. |
| Percentage of Participants Who Maintained CMV Viremia Clearance and CMV Infection Symptom Control at Week 8 Through Weeks 12, 16 and 20 | At Week 8 through Weeks 12, 16 and 20 | The confirmed viremia clearance was defined as a plasma CMV DNA concentration below the LLOQ (i.e., \<34.5 IU/mL) when assessed by the COBAS® 8800/COBAS® CMV Test, in two consecutive post-baseline samples, separated by at least 5 days. Percentage of participants who maintained combined CMV viremia clearance and CMV infection symptom control at Week 8 Through Weeks 12, 16 and 20 were reported. |
Countries
Japan
Participant flow
Recruitment details
The study was conducted at 23 sites in Japan from 18 January 2022 to 27 June 2023.
Pre-assignment details
Japanese participants with cytomegalovirus (CMV) infection were enrolled to receive maribavir treatment in this study.
Participants by arm
| Arm | Count |
|---|---|
| Maribavir Participants received maribavir 400 milligrams (mg), oral tablet, twice a day (BID) for up to 8 weeks. | 41 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Maribavir |
|---|---|
| Age, Continuous | 53.9 years STANDARD_DEVIATION 11.16 |
| Body Mass Index (BMI) | 21.26 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 3.538 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 164.46 centimetres (cm) STANDARD_DEVIATION 8.702 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 41 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Japan | 41 Participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 20 Participants |
| Weight | 57.47 kilograms (kg) STANDARD_DEVIATION 10.707 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 41 |
| other Total, other adverse events | 26 / 41 |
| serious Total, serious adverse events | 13 / 41 |
Outcome results
Primary
Number of Participants With Clinically Meaningful Abnormalities in Clinical Laboratory Parameters
Clinical laboratory parameters included evaluations of hematology, chemistry, urinalysis. Any clinically meaningful change in clinical laboratory parameters which were deemed clinically significant by the investigator were reported.
Time frame: From first dose of study drug up to Week 20
Population: Safety set included of all participants who had taken at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maribavir | Number of Participants With Clinically Meaningful Abnormalities in Clinical Laboratory Parameters | 0 Participants |
Primary
Number of Participants With Clinically Meaningful Abnormalities in Physical Examination Findings
Physical examination included assessments of the head, eyes, ears, nose, throat, neck, lymph nodes, and the cardiovascular, dermatological, musculoskeletal, respiratory, gastrointestinal, genitourinary, and neurological systems. Any clinically meaningful change in physical examination which were deemed clinically significant by the investigator were reported.
Time frame: From first dose of study drug up to Week 20
Population: Safety set included of all participants who had taken at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maribavir | Number of Participants With Clinically Meaningful Abnormalities in Physical Examination Findings | 0 Participants |
Primary
Number of Participants With Clinically Meaningful Changes in Electrocardiograms (ECGs)
12-lead ECG were evaluated. Any change in ECG assessments which are deemed clinically meaningful by the investigator were reported.
Time frame: From first dose of study drug up to Week 20
Population: Safety set included of all participants who had taken at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maribavir | Number of Participants With Clinically Meaningful Changes in Electrocardiograms (ECGs) | 0 Participants |
Primary
Number of Participants With Clinically Meaningful Changes in Vital Signs
Vital sign assessments included blood pressure, pulse, respiratory rate and body temperature. Any clinically meaningful change in vital signs which were deemed clinically significant by the investigator were reported.
Time frame: From first dose of study drug up to Week 20
Population: Safety set included of all participants who had taken at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maribavir | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 Participants |
Primary
Number of Participants With Events of Immunosuppressant Drug Level Increased in Blood
Immunosuppressant drug concentration testing was solely for participants who received immunosuppressive therapy with tacrolimus, cyclosporine, or everolimus. The number of participants with an increased level of at least one immunosuppressant drug was reported.
Time frame: From first dose of study drug up to Week 8
Population: Safety set included of all participants who had taken at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maribavir | Number of Participants With Events of Immunosuppressant Drug Level Increased in Blood | 1 Participants |
Primary
Number of Participants With TEAEs Leading to Treatment Discontinuation With Maribavir
The number of participants with TEAEs leading to maribavir study treatment discontinuation (including treatment interruption or withdrawal) were reported.
Time frame: From first dose of study drug up to Week 20
Population: Safety set included of all participants who had taken at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maribavir | Number of Participants With TEAEs Leading to Treatment Discontinuation With Maribavir | 9 Participants |
Primary
Number of Participants With TEAEs of New Onset of Acute or Chronic Graft-versus-host Disease (GVHD), Graft Rejection, or Graft Loss
New onset of acute or chronic GVHD assessed as TEAEs, and graft rejection, or graft loss assessed were reported.
Time frame: From first dose of study drug up to Week 20
Population: Safety set included of all participants who had taken at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Maribavir | Number of Participants With TEAEs of New Onset of Acute or Chronic Graft-versus-host Disease (GVHD), Graft Rejection, or Graft Loss | TEAEs of Acute or Chronic GVHD | 2 Participants |
| Maribavir | Number of Participants With TEAEs of New Onset of Acute or Chronic Graft-versus-host Disease (GVHD), Graft Rejection, or Graft Loss | TEAEs of Graft Rejection, or Graft Loss | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
A TEAEs was defined as any event emerging or manifesting at or after the initiation of treatment with an investigational product or medicinal product or any existing event that worsened in either intensity or frequency following exposure to the investigational product or medicinal product. An SAE was any untoward medical occurrence or effect that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability / incapacity, was a congenital anomaly / birth defect or was medically important due to other reasons than the above mentioned criteria.
Time frame: From first dose of study drug up to Week 20
Population: Safety set included of all participants who had taken at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Maribavir | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 39 Participants |
| Maribavir | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 13 Participants |
Primary
Percentage of Participants Who Achieved Confirmed Clearance of Plasma CMV Deoxyribose Nucleic Acid (DNA) at Week 8
The confirmed viremia clearance was defined as a plasma CMV DNA concentration below the lower limit of quantification (LLOQ) (that is \[i.e.\], less than \[\<\] 34.5 international units per milliliter \[IU/mL\]) when assessed by the COBAS® 8800/COBAS® CMV Test, in two consecutive post-baseline samples, separated by at least 5 days. To be considered a responder for the primary endpoint, the participant must have received exclusively study-assigned treatment (regardless of whether study-assigned treatment was completed).
Time frame: At Week 8
Population: FAS included of all participants who had taken at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maribavir | Percentage of Participants Who Achieved Confirmed Clearance of Plasma CMV Deoxyribose Nucleic Acid (DNA) at Week 8 | 68.3 percentage of participants |
Secondary
Change From Baseline in Plasma CMV Viremia Load
The change from baseline in plasma CMV viral load, i.e., plasma CMV DNA concentration was assessed and reported.
Time frame: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 14, 16, 18 and 20
Population: FAS included of all participants who had taken at least 1 dose of study treatment. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable for the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maribavir | Change From Baseline in Plasma CMV Viremia Load | Change at Week 20 | -1.9734 IU/mL | Standard Deviation 0.91902 |
| Maribavir | Change From Baseline in Plasma CMV Viremia Load | Change at Week 1 | -0.7821 IU/mL | Standard Deviation 0.6235 |
| Maribavir | Change From Baseline in Plasma CMV Viremia Load | Change at Week 2 | -1.4813 IU/mL | Standard Deviation 0.7154 |
| Maribavir | Change From Baseline in Plasma CMV Viremia Load | Change at Week 3 | -1.7935 IU/mL | Standard Deviation 0.86625 |
| Maribavir | Change From Baseline in Plasma CMV Viremia Load | Change at Week 4 | -1.9555 IU/mL | Standard Deviation 0.90538 |
| Maribavir | Change From Baseline in Plasma CMV Viremia Load | Change at Week 5 | -2.0383 IU/mL | Standard Deviation 0.97092 |
| Maribavir | Change From Baseline in Plasma CMV Viremia Load | Change at Week 6 | -1.9922 IU/mL | Standard Deviation 1.02593 |
| Maribavir | Change From Baseline in Plasma CMV Viremia Load | Change at Week 7 | -1.9718 IU/mL | Standard Deviation 1.10335 |
| Maribavir | Change From Baseline in Plasma CMV Viremia Load | Change at Week 8 | -1.7971 IU/mL | Standard Deviation 1.28349 |
| Maribavir | Change From Baseline in Plasma CMV Viremia Load | Change at Week 9 | -1.7771 IU/mL | Standard Deviation 0.92825 |
| Maribavir | Change From Baseline in Plasma CMV Viremia Load | Change at Week 10 | -1.6819 IU/mL | Standard Deviation 0.93517 |
| Maribavir | Change From Baseline in Plasma CMV Viremia Load | Change at Week 11 | -1.5275 IU/mL | Standard Deviation 0.9443 |
| Maribavir | Change From Baseline in Plasma CMV Viremia Load | Change at Week 12 | -1.5383 IU/mL | Standard Deviation 1.07532 |
| Maribavir | Change From Baseline in Plasma CMV Viremia Load | Change at Week 14 | -1.7712 IU/mL | Standard Deviation 1.08735 |
| Maribavir | Change From Baseline in Plasma CMV Viremia Load | Change at Week 16 | -1.7042 IU/mL | Standard Deviation 1.05775 |
| Maribavir | Change From Baseline in Plasma CMV Viremia Load | Change at Week 18 | -1.9569 IU/mL | Standard Deviation 0.83577 |
Secondary
Minimum Observed Plasma Concentration (Cmin) of Maribavir
Cmin (pre-dose) of maribavir was assessed.
Time frame: At Weeks 1, 4, and 8: Pre-dose
Population: Pharmacokinetic set included of all participants in the safety set who had plasma sample drawn and tested for maribavir concentrations. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable for the specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Maribavir | Minimum Observed Plasma Concentration (Cmin) of Maribavir | Week 1: Pre-dose | 10.08 micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 105.73 |
| Maribavir | Minimum Observed Plasma Concentration (Cmin) of Maribavir | Week 4: Pre-dose | 12.31 micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 108.05 |
| Maribavir | Minimum Observed Plasma Concentration (Cmin) of Maribavir | Week 8: Pre-dose | 12.37 micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 95.26 |
Secondary
Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance at Week 8 to be Less Than (<) 137 IU/mL
The confirmed CMV viremia clearance at Week 8 was defined as plasma CMV DNA concentrations \<137 IU/mL, in 2 consecutive post-baseline samples separated by at least 5 days, regardless of whether study treatment was discontinued before the end of the stipulated 8 weeks of therapy.
Time frame: At Week 8
Population: FAS included of all participants who had taken at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maribavir | Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance at Week 8 to be Less Than (<) 137 IU/mL | 73.2 percentage of participants |
Secondary
Percentage of Participants Who Maintained CMV Viremia Clearance and CMV Infection Symptom Control at Week 8 Through Weeks 12, 16 and 20
The confirmed viremia clearance was defined as a plasma CMV DNA concentration below the LLOQ (i.e., \<34.5 IU/mL) when assessed by the COBAS® 8800/COBAS® CMV Test, in two consecutive post-baseline samples, separated by at least 5 days. Percentage of participants who maintained combined CMV viremia clearance and CMV infection symptom control at Week 8 Through Weeks 12, 16 and 20 were reported.
Time frame: At Week 8 through Weeks 12, 16 and 20
Population: FAS included of all participants who had taken at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maribavir | Percentage of Participants Who Maintained CMV Viremia Clearance and CMV Infection Symptom Control at Week 8 Through Weeks 12, 16 and 20 | At Week 8 | 68.3 percentage of participants |
| Maribavir | Percentage of Participants Who Maintained CMV Viremia Clearance and CMV Infection Symptom Control at Week 8 Through Weeks 12, 16 and 20 | At Week 12 | 34.1 percentage of participants |
| Maribavir | Percentage of Participants Who Maintained CMV Viremia Clearance and CMV Infection Symptom Control at Week 8 Through Weeks 12, 16 and 20 | At Week 16 | 29.3 percentage of participants |
| Maribavir | Percentage of Participants Who Maintained CMV Viremia Clearance and CMV Infection Symptom Control at Week 8 Through Weeks 12, 16 and 20 | At Week 20 | 26.8 percentage of participants |
Secondary
Percentage of Participants With Any Mutations in the CMV Genes Conferring Resistance to Maribavir
Plasma samples were obtained and tested to identify mutations in the viral UL97 and UL54 genes confer resistance to maribavir. Percentage of participants with any mutations in the CMV genes conferring resistance to maribavir was reported.
Time frame: From first dose of study drug up to Week 20
Population: FAS included of all participants who had taken at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maribavir | Percentage of Participants With Any Mutations in the CMV Genes Conferring Resistance to Maribavir | 12.2 percentage of participants |
Secondary
Percentage of Participants With Recurrence of CMV Viremia During Study Treatment and in the Follow-Up Period After the Participants Are Discontinued From Study Treatment and While On/Off Study Assigned Treatment
Recurrence of CMV viremia was defined as plasma CMV DNA concentration \>= lower limit of quantification (LLOQ, i.e. \>=34.5 IU/mL) when assessed by COBAS® 8800/COBAS® CMV Test in 2 consecutive plasma samples at least 5 days apart, after being unquantifiable (\<LLOQ, i.e. \<34.5 IU/mL) for at least 5 days in 2 consecutive samples during the first 8 weeks of the study. Study Treatment: The first stipulated 8 weeks treatment. Follow up period: period started after completion of stipulated 8 weeks treatment to Week 20. While on study assigned treatment: period over which participants received actual dosing regardless of stipulated 8 weeks completion (Week 8 or earlier). While off study assigned treatment: period after study treatment, regardless of stipulated 8 weeks completion (Week 8 or earlier up to Week 20).
Time frame: Study treatment: Week 0 to Week 8; Follow-up Period:Week 9 to Week 20; At Any time during study:Week 0 to Week 20; While on study assigned treatment: Week 0 to EOT(Week 8 or earlier); While off study assigned treatment: EOT (Week 8 or earlier) to Week 20
Population: FAS included of all participants who had taken at least 1 dose of study treatment. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maribavir | Percentage of Participants With Recurrence of CMV Viremia During Study Treatment and in the Follow-Up Period After the Participants Are Discontinued From Study Treatment and While On/Off Study Assigned Treatment | Study Treatment: (Week 0 to Week 8) | 13.9 percentage of participants |
| Maribavir | Percentage of Participants With Recurrence of CMV Viremia During Study Treatment and in the Follow-Up Period After the Participants Are Discontinued From Study Treatment and While On/Off Study Assigned Treatment | Follow-up Period: (Week 9 to Week 20) | 44.4 percentage of participants |
| Maribavir | Percentage of Participants With Recurrence of CMV Viremia During Study Treatment and in the Follow-Up Period After the Participants Are Discontinued From Study Treatment and While On/Off Study Assigned Treatment | At Any Time During the Study (Week 0 to Week 20) | 58.3 percentage of participants |
| Maribavir | Percentage of Participants With Recurrence of CMV Viremia During Study Treatment and in the Follow-Up Period After the Participants Are Discontinued From Study Treatment and While On/Off Study Assigned Treatment | While on Study Assigned Treatment (Week 0 to End of Treatment [EOT] [Week 8 or earlier]) | 8.3 percentage of participants |
| Maribavir | Percentage of Participants With Recurrence of CMV Viremia During Study Treatment and in the Follow-Up Period After the Participants Are Discontinued From Study Treatment and While On/Off Study Assigned Treatment | While off Study Assigned Treatment (EOT [Week 8 or earlier] to Week 20) | 50.0 percentage of participants |
Secondary
Percentage of Participants With Recurrence of Confirmed CMV Viremia During Follow-up Period in Participants With Confirmed Viremia Clearance at Week 8 Who Required Additional Anti-CMV Treatment
Recurrence of confirmed CMV viremia was defined as plasma CMV DNA concentration greater than or equal to (\>= 34.5 IU/mL) LLOQ when assessed by the COBAS® 8800/COBAS®CMV Test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance.
Time frame: From Week 9 up to Week 20
Population: FAS included of all participants who had taken at least 1 dose of study treatment. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maribavir | Percentage of Participants With Recurrence of Confirmed CMV Viremia During Follow-up Period in Participants With Confirmed Viremia Clearance at Week 8 Who Required Additional Anti-CMV Treatment | 42.9 percentage of participants |
Secondary
Time to First Confirmed CMV Viremia Clearance
Time to first confirmed viremia clearance was defined as time from the start date of first dose of study treatment to the date of confirmed viremia clearance (event), or the date of last CMV DNA assessment on study before the initiation of alternative anti-CMV treatment (censored). The time to first confirmed CMV viremia clearance was calculated as date of first confirmed CMV viremia clearance - randomization date + 1). The date of first confirmed CMV viremia clearance was the date of first of two consecutive samples with plasma CMV DNA \<LLOQ that meet the criteria of confirmed CMV viremia clearance.
Time frame: From first dose of study drug up to Week 20
Population: FAS included of all participants who had taken at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maribavir | Time to First Confirmed CMV Viremia Clearance | 22.0 days |