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

Cytomegalovirus (CMV) Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05137717
• Other study ID #: TAK-620-3001
• Secondary ID: jRCT2021210056
• Status: Completed
• Phase: Phase 3
• Start date: December 23, 2021
• Est. completion date: June 27, 2023

Study information

• Verified date: June 2023
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: June 27, 2023
• Est. primary completion date: June 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cytomegalovirus (CMV)
• Cytomegalovirus Infections

Intervention

Drug:
• Maribavir
Maribavir tablets

Locations

Country	Name	City	State
Japan	Chiba University Hospital	Chiba
Japan	Kyushu University Hospital	Fukuoka-shi	Fukuoka
Japan	Fukushima Medical University Hospital	Fukushima
Japan	Imamura General Hospital	Kagoshima-shi	Kagoshima
Japan	Kyoto University Hospital	Kyoto
Japan	The Jikei University Hospital	Minato-ku	Tokyo
Japan	Toranomon Hospital	Minato-ku	Tokyo
Japan	Okayama University Hospital	Okayama
Japan	Osaka Metropolitan University Hospital	Osaka
Japan	Osaka International Cancer Institute	Osaka-shi	Osaka
Japan	Jichi Medical University Saitama Medical Center	Saitama
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Sapporo City General Hospital	Sapporo	Hokkaido
Japan	Sapporo Hokuyu Hospital	Sapporo-Shi	Hokkaido
Japan	Jichi Medical University Hospital	Shimotsuke	Tochigi
Japan	Keio University Hospital	Shinjuku-ku	Tokyo
Japan	Yochomachi Clinic	Shinjuku-ku	Tokyo
Japan	Osaka University Hospital	Suita	Osaka
Japan	Ehime University Hospital	Toon	Ehime
Japan	University of Tsukuba Hospital	Tsukuba-shi	Ibaraki

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Number of Participants with Adverse Events Leading to Interruption with Maribavir		Up to Week 20
Primary	Number of Participants with Adverse Events Leading to Permanent Treatment Discontinuation with Maribavir		Up to Week 20
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	Change from Baseline in Plasma CMV Viremia Load		Baseline, Up to Week 20
Secondary	Percentage of Participants with Recurrences of CMV Resistance Mutations after Maribavir Treatment		Up to Week 20
Secondary	Number of Kinds for CMV Genes Mutation Conferring Resistance to Maribavir after Maribavir Treatment		Up to Week 20
Secondary	Percentage of Participants who Achieved Confirmed Clearance at 137 IU/mL or Less of Plasma CMV DNA (CMV Viremia Clearance)		Up to Week 8
Secondary	Maribavir Minimum Concentration (Cmin)		Week 1, 4, and 8

External Links

•   To obtain more information on the study, click here/on this link