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

NCT05137717 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: TAK-620-3001jRCT2021210056
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 20

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.

Conditions

Cytomegalovirus (CMV)

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (8)

• 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

• Time to First 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

  From Week 9 up to Week 20

• 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

• 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

Study Arms (1)

Maribavir

EXPERIMENTAL

Maribavir 400 milligrams (mg), tablets, orally twice a day (BID) for up to 8 weeks.

Drug: Maribavir

Interventions

Maribavir DRUG

Maribavir tablets

Also known as: SHP620, TAK-620

Maribavir

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (20)

Ehime University Hospital

Tōon, Ehime, Japan

Location

Kyushu University Hospital

Fukuoka, Fukuoka, Japan

Location

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

Location

Sapporo City General Hospital

Sapporo, Hokkaido, Japan

Location

Sapporo Hokuyu Hospital

Sapporo, Hokkaido, Japan

Location

University of Tsukuba Hospital

Tsukuba, Ibaraki, Japan

Location

Imamura General Hospital

Kagoshima, Kagoshima-ken, Japan

Location

Osaka International Cancer Institute

Osaka, Osaka, Japan

Location

Osaka University Hospital

Suita, Osaka, Japan

Location

Jichi Medical University Hospital

Shimotsuke, Tochigi, Japan

Location

The Jikei University Hospital

Minato-ku, Tokyo, Japan

Location

Toranomon Hospital

Minato-ku, Tokyo, Japan

Location

Keio University Hospital

Shinjuku-ku, Tokyo, Japan

Location

Yochomachi Clinic

Shinjuku-ku, Tokyo, Japan

Location

Chiba University Hospital

Chiba, Japan

Location

Fukushima Medical University Hospital

Fukushima, Japan

Location

Kyoto University Hospital

Kyoto, Japan

Location

Okayama University Hospital

Okayama, Japan

Location

Osaka Metropolitan University Hospital

Osaka, Japan

Location

Jichi Medical University Saitama Medical Center

Saitama, Japan

Location

Related Links

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

MeSH Terms

Interventions

maribavir

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2021
• First Posted: November 30, 2021
• Study Start: January 18, 2022
• Primary Completion: June 27, 2023
• Study Completion: June 27, 2023
• Last Updated: July 9, 2024
• Results First Posted: July 9, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.

Locations

JP (20)