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

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)

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.

Study Overview

• Status: Completed
• Conditions: Cytomegalovirus (CMV)
• Intervention / Treatment: Drug: Maribavir

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Maribavir; Maribavir 400 milligrams (mg), tablets, orally twice a day (BID) for up to 8 weeks.	Drug: Maribavir; Maribavir tablets; Other Names: SHP620; TAK-620

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	At Week 8
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.	From first dose of study drug up to Week 20
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.	From first dose of study drug up to Week 20
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.	From first dose of study drug up to Week 20
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.	From first dose of study drug up to Week 20
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.	From first dose of study drug up to Week 20
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.	From first dose of study drug up to Week 20
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.	From first dose of study drug up to Week 8
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.	From first dose of study drug up to Week 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At Week 8 through Weeks 12, 16 and 20
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.	From first dose of study drug up to Week 20
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.	From Week 9 up to Week 20
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.	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 14, 16, 18 and 20
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).	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
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.	From first dose of study drug up to Week 20
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.	At Week 8
Minimum Observed Plasma Concentration (Cmin) of Maribavir	Cmin (pre-dose) of maribavir was assessed.	At Weeks 1, 4, and 8: Pre-dose

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2022
• Primary Completion (Actual): June 27, 2023
• Study Completion (Actual): June 27, 2023

Study Registration Dates

• First Submitted: November 25, 2021
• First Submitted That Met QC Criteria: November 25, 2021
• First Posted (Actual): November 30, 2021

Study Record Updates

• Last Update Posted (Actual): July 9, 2024
• Last Update Submitted That Met QC Criteria: July 3, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Cytomegalovirus Infections; Anti-Infective Agents; Antiviral Agents; Maribavir
• Other Study ID Numbers: TAK-620-3001; jRCT2021210056 (Registry Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• 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