Clinical trial NCT05137717: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cytomegalovirus (CMV)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2021-11-30
Enrollment: 41
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Who Achieved Confirmed Clearance of Plasma CMV Deoxyribose Nucleic Acid (DNA) at Week 8
timeFrame: At Week 8
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: From first dose of study drug up to Week 20
measure: Number of Participants With TEAEs Leading to Treatment Discontinuation With Maribavir
timeFrame: From first dose of study drug up to Week 20
measure: Number of Participants With Clinically Meaningful Changes in Vital Signs
timeFrame: From first dose of study drug up to Week 20
measure: Number of Participants With Clinically Meaningful Abnormalities in Physical Examination Findings
timeFrame: From first dose of study drug up to Week 20
measure: Number of Participants With Clinically Meaningful Abnormalities in Clinical Laboratory Parameters
timeFrame: From first dose of study drug up to Week 20
measure: Number of Participants With Clinically Meaningful Changes in Electrocardiograms (ECGs)
timeFrame: From first dose of study drug up to Week 20
measure: Number of Participants With Events of Immunosuppressant Drug Level Increased in Blood
timeFrame: From first dose of study drug up to Week 8
measure: Number of Participants With TEAEs of New Onset of Acute or Chronic Graft-versus-host Disease (GVHD), Graft Rejection, or Graft Loss
timeFrame: From first dose of study drug up to Week 20
Secondary outcomes:
measure: Percentage of Participants Who Maintained CMV Viremia Clearance and CMV Infection Symptom Control at Week 8 Through Weeks 12, 16 and 20
timeFrame: At Week 8 through Weeks 12, 16 and 20
measure: Time to First Confirmed CMV Viremia Clearance
timeFrame: From first dose of study drug up to Week 20
measure: 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
timeFrame: From Week 9 up to Week 20
measure: Change From Baseline in Plasma CMV Viremia Load
timeFrame: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 14, 16, 18 and 20
measure: 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
timeFrame: 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
measure: Percentage of Participants With Any Mutations in the CMV Genes Conferring Resistance to Maribavir
timeFrame: From first dose of study drug up to Week 20
measure: Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance at Week 8 to be Less Than (<) 137 IU/mL
timeFrame: At Week 8
measure: Minimum Observed Plasma Concentration (Cmin) of Maribavir
timeFrame: At Weeks 1, 4, and 8: Pre-dose
Other outcomes:
Locations:
city: Toon
country: Japan
facility: Ehime University Hospital
state: Ehime
city: Fukuoka-shi
country: Japan
facility: Kyushu University Hospital
state: Fukuoka
city: Sapporo-Shi
country: Japan
facility: Sapporo Hokuyu Hospital
state: Hokkaido
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Sapporo
country: Japan
facility: Sapporo City General Hospital
state: Hokkaido
city: Tsukuba-shi
country: Japan
facility: University of Tsukuba Hospital
state: Ibaraki
city: Kagoshima-shi
country: Japan
facility: Imamura General Hospital
state: Kagoshima
city: Osaka-shi
country: Japan
facility: Osaka International Cancer Institute
state: Osaka
city: Suita
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Shimotsuke
country: Japan
facility: Jichi Medical University Hospital
state: Tochigi
city: Minato-ku
country: Japan
facility: The Jikei University Hospital
state: Tokyo
city: Minato-ku
country: Japan
facility: Toranomon Hospital
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Yochomachi Clinic
state: Tokyo
city: Chiba
country: Japan
facility: Chiba University Hospital
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: Osaka Metropolitan University Hospital
city: Saitama
country: Japan
facility: Jichi Medical University Saitama Medical Center
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: