Back to resultsA Study of Maribavir in Japanese People With Cytomegalovirus (CMV) Infection
Primary Purpose
Cytomegalovirus (CMV)
Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
Maribavir
Sponsored by
About this trial
This is an interventional treatment trial for Cytomegalovirus (CMV)
Eligibility Criteria
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.
Sites / Locations
- Ehime University Hospital
- Kyushu University Hospital
- Sapporo Hokuyu Hospital
- Hokkaido University Hospital
- Sapporo City General Hospital
- University of Tsukuba Hospital
- Imamura General Hospital
- Osaka International Cancer Institute
- Osaka University Hospital
- Jichi Medical University Hospital
- The Jikei University Hospital
- Toranomon Hospital
- Keio University Hospital
- Yochomachi Clinic
- Chiba University Hospital
- Fukushima Medical University Hospital
- Kyoto University Hospital
- Okayama University Hospital
- Osaka Metropolitan University Hospital
- Jichi Medical University Saitama Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Maribavir
Arm Description
Maribavir 400 milligrams (mg), tablets, orally twice a day (BID) for up to 8 weeks.
Outcomes
Primary Outcome Measures
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.
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.
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.
Number of Participants with Adverse Events Leading to Interruption with Maribavir
Number of Participants with Adverse Events Leading to Permanent Treatment Discontinuation with Maribavir
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.
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.
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.
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.
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.
Number of Participants with TEAEs of New Onset of Acute or Chronic Graft-versus-host Disease (GVHD), Graft Rejection, or Graft Loss
Secondary Outcome Measures
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.
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.
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.
Change from Baseline in Plasma CMV Viremia Load
Percentage of Participants with Recurrences of CMV Resistance Mutations after Maribavir Treatment
Number of Kinds for CMV Genes Mutation Conferring Resistance to Maribavir after Maribavir Treatment
Percentage of Participants who Achieved Confirmed Clearance at 137 IU/mL or Less of Plasma CMV DNA (CMV Viremia Clearance)
Maribavir Minimum Concentration (Cmin)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05137717
Brief Title
A Study of Maribavir in Japanese People With Cytomegalovirus (CMV) Infection
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
December 23, 2021 (Actual)
Primary Completion Date
June 27, 2023 (Actual)
Study Completion Date
June 27, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cytomegalovirus (CMV)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Maribavir
Arm Type
Experimental
Arm Description
Maribavir 400 milligrams (mg), tablets, orally twice a day (BID) for up to 8 weeks.
Intervention Type
Drug
Intervention Name(s)
Maribavir
Other Intervention Name(s)
SHP620, TAK-620
Intervention Description
Maribavir tablets
Primary Outcome Measure Information:
Title
Percentage of Participants Confirmed Cytomegalovirus (CMV) Viremia Clearance (Clearance of Plasma CMV DNA)
Description
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.
Time Frame
Up to Week 8
Title
Number of Participants with Serious Adverse Events (SAE)
Description
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.
Time Frame
Up to Week 20
Title
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
Description
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.
Time Frame
Up to Week 20
Title
Number of Participants with Adverse Events Leading to Interruption with Maribavir
Time Frame
Up to Week 20
Title
Number of Participants with Adverse Events Leading to Permanent Treatment Discontinuation with Maribavir
Time Frame
Up to Week 20
Title
Number of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs
Description
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.
Time Frame
Up to Week 20
Title
Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings Reported as TEAEs
Description
Any change in physical examination findings by the investigator will be recorded as TEAEs.
Time Frame
Up to Week 20
Title
Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters Reported as TEAEs
Description
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.
Time Frame
Up to Week 20
Title
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as TEAEs
Description
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.
Time Frame
Up to Week 20
Title
Immunosuppressant Drug Concentration Levels in Blood
Description
Immunosuppressant drug concentration levels solely for participants receiving immunosuppressive therapy at baseline, Day 4, Week 1, 8, and 9 will be accessed.
Time Frame
Baseline, Day 4, Week 1, 8 and 9
Title
Number of Participants with TEAEs of New Onset of Acute or Chronic Graft-versus-host Disease (GVHD), Graft Rejection, or Graft Loss
Time Frame
Up to Week 20
Secondary Outcome Measure Information:
Title
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
Description
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.
Time Frame
At Week 8 through Weeks 12, 16 and 20
Title
Time to First Confirmed CMV Viremia Clearance
Description
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.
Time Frame
Up to Week 20
Title
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
Description
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.
Time Frame
Up to Week 20
Title
Change from Baseline in Plasma CMV Viremia Load
Time Frame
Baseline, Up to Week 20
Title
Percentage of Participants with Recurrences of CMV Resistance Mutations after Maribavir Treatment
Time Frame
Up to Week 20
Title
Number of Kinds for CMV Genes Mutation Conferring Resistance to Maribavir after Maribavir Treatment
Time Frame
Up to Week 20
Title
Percentage of Participants who Achieved Confirmed Clearance at 137 IU/mL or Less of Plasma CMV DNA (CMV Viremia Clearance)
Time Frame
Up to Week 8
Title
Maribavir Minimum Concentration (Cmin)
Time Frame
Week 1, 4, and 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Ehime University Hospital
City
Toon
State/Province
Ehime
Country
Japan
Facility Name
Kyushu University Hospital
City
Fukuoka-shi
State/Province
Fukuoka
Country
Japan
Facility Name
Sapporo Hokuyu Hospital
City
Sapporo-Shi
State/Province
Hokkaido
Country
Japan
Facility Name
Hokkaido University Hospital
City
Sapporo
State/Province
Hokkaido
Country
Japan
Facility Name
Sapporo City General Hospital
City
Sapporo
State/Province
Hokkaido
Country
Japan
Facility Name
University of Tsukuba Hospital
City
Tsukuba-shi
State/Province
Ibaraki
Country
Japan
Facility Name
Imamura General Hospital
City
Kagoshima-shi
State/Province
Kagoshima
Country
Japan
Facility Name
Osaka International Cancer Institute
City
Osaka-shi
State/Province
Osaka
Country
Japan
Facility Name
Osaka University Hospital
City
Suita
State/Province
Osaka
Country
Japan
Facility Name
Jichi Medical University Hospital
City
Shimotsuke
State/Province
Tochigi
Country
Japan
Facility Name
The Jikei University Hospital
City
Minato-ku
State/Province
Tokyo
Country
Japan
Facility Name
Toranomon Hospital
City
Minato-ku
State/Province
Tokyo
Country
Japan
Facility Name
Keio University Hospital
City
Shinjuku-ku
State/Province
Tokyo
Country
Japan
Facility Name
Yochomachi Clinic
City
Shinjuku-ku
State/Province
Tokyo
Country
Japan
Facility Name
Chiba University Hospital
City
Chiba
Country
Japan
Facility Name
Fukushima Medical University Hospital
City
Fukushima
Country
Japan
Facility Name
Kyoto University Hospital
City
Kyoto
Country
Japan
Facility Name
Okayama University Hospital
City
Okayama
Country
Japan
Facility Name
Osaka Metropolitan University Hospital
City
Osaka
Country
Japan
Facility Name
Jichi Medical University Saitama Medical Center
City
Saitama
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing Access Criteria
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.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Links:
URL
https://clinicaltrials.takeda.com/study-detail/61a671acf571d4002a64b438
Description
To obtain more information on the study, click here/on this link
Learn more about this trial
A Study of Maribavir in Japanese People With Cytomegalovirus (CMV) Infection
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