A Study of Maribavir in Chinese Adults With Cytomegalovirus (CMV) Infections

Official title

An Open-label, Single-arm Study to Evaluate the Safety, Tolerability, Efficacy and Pharmacokinetics of Maribavir in Chinese Transplant Recipients With Cytomegalovirus (CMV) Infections That Are Refractory or Resistant to Treatment With Ganciclovir, Valganciclovir, Cidofovir or Foscarnet

Overview

The main aim of this study is to learn how safe maribavir is in Chinese adults who have undergone hematopoietic stem cell or organ transplantation and have a cytomegalovirus (CMV) infection and how well they tolerate treatment with maribavir. Other aims are to see how effective maribavir is in treating CMV infection and getting rid of the symptoms, the recurrence rate of CMV infection after treatment with maribavir and if the treatment is required again. Researchers will also check for changes (mutations) occurring in the virus which may cause treatment with maribavir to no longer work well or to not work at all (resistance to maribavir). The participants will be treated with maribavir for 8 weeks. During the study, participants will visit their study clinic 18 times.

Interventions

• Drug Maribavir
  Maribavir tablets

Primary outcome measures

• Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAE), and Adverse Events of Special interest (AESIs) [Time frame: From first dose of study drug up to Week 20]
• Number of Participants With Clinically Significant Changes in Vital Signs [Time frame: From first dose of study drug up to Week 20]
• Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters [Time frame: From first dose of study drug up to Week 20]
• Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings [Time frame: From first dose of study drug up to Week 20]
• Number of Participants Who will Discontinue From the Study Drug and Study [Time frame: From first dose of study drug up to Week 20]

Secondary outcome measures (12)

• Percentage of Participants With Confirmed Clearance of Plasma CMV Deoxyribose Nucleic Acid (DNA) (CMV Viremia Clearance) at Week 8 [Time frame: At Week 8]
• Percentage of Participants With Achievement of CMV Viremia Clearance and CMV Infection Symptom Control at Weeks 8, 12, 16, and 20 [Time frame: At Weeks 8, 12, 16 and 20]
• Percentage of Participants With Achievement of CMV Viremia Clearance and CMV Infection Symptom Control at Week 8 (After Completion of 8 Weeks Therapy) [Time frame: At Week 8]
• Percentage of Participants With Achievement of CMV Viremia Clearance and CMV Infection Symptom Control After Completion of 8 weeks Therapy Followed by Maintenance of This Treatment Effect Through Weeks 12, 16 and 20 [Time frame: At Weeks 12, 16 and 20]
• Percentage of Participants With Recurrence of CMV Viremia During the First 8 Weeks and Through Week 12 to Week 20 [Time frame: From first dose of study drug up to Week 8, and through Week 12 to Week 20]
• Percentage of Participants With Recurrence of CMV Viremia During on Treatment and off Treatment [Time frame: From first dose of study drug up to Week 8 (on treatment) and Week 20 (off treatment)]
• Percentage of Participants With Recurrence of CMV Viremia Requiring Alternative Treatment After Achieving CMV Viremia Clearance at Study Week 8 [Time frame: At Week 8]
• Percentage of Participants With Mutations in the CMV Genes Conferring Resistance to Maribavir [Time frame: Up to Week 20]
• Number of Participants With All-cause Mortality During the Study [Time frame: Up to Week 20]
• Maximum Observed Plasma Concentration (Cmax) at Steady State for Maribavir [Time frame: Week 1, Day 7: Pre-dose, 0.5, 1.5, 3, 4, 6, 8, and 12 hours post-dose]
• Time to Reach Cmax (Tmax) at Steady State for Maribavir [Time frame: Week 1, Day 7: Pre-dose, 0.5, 1.5, 3, 4, 6, 8 and 12 hours post-dose]
• Minimum Observed Plasma Concentration (Cmin) for Maribavir [Time frame: Pre-dose and at Weeks 1, 4, and 8]

Eligibility criteria

Inclusion criteria

• The participant or the participant's legally acceptable representative is willing and able to understand and fully comply with study procedures and requirements, in the opinion of the investigator.
• The participant/participant's legally representative has provided informed consent (that is, in writing, documented via a signed and dated informed consent form \[ICF\]) and any required privacy authorization prior to the initiation of any study procedures.
• The participant is aged 18 years or older (ie, greater than or equal to \[>=\] 18 years) at the time of signing the ICF.
• The participant must be of Chinese descent, defined as born in China and having Chinese parents and Chinese maternal and paternal grandparents.
• The participant must be a recipient of hematopoietic stem cell or solid organ transplant.
• The participant must have a documented CMV infection in whole blood or plasma, with a screening value of >=1,365 International unit per milliliter IU/mL in whole blood or >=455 IU/mL in plasma in 2 consecutive assessments, separated by at least 1 day, as determined by local laboratory quantitative polymerase chain reaction (qPCR) or comparable quantitative CMV DNA results. Both samples should be taken within 14 days prior to receiving the investigational product with second sample obtained within 5 days prior to receiving the investigational product. The same laboratory and same sample type (whole blood or plasma) must be used for these assessments.
• The participant must have a current CMV infection that is refractory to the most recently administered of the 4 anti-CMV treatment agent(s) eg, intravenous (IV) ganciclovir/oral valganciclovir, IV foscarnet, or IV cidofovir. Refractory is defined as documented failure to achieve greater than (>) 1 log10 (common logarithm to base 10) decrease in CMV DNA level in whole blood or plasma after a 14 day or longer treatment period with the above 4 agents.
• Participants who have documentation of 1 or more CMV genetic mutations associated with resistance to ganciclovir/valganciclovir, cidofovir, or foscarnet must also meet the definition of refractory CMV infection.
• Have all the following results as part of screening laboratory assessments:

• Absolute neutrophil count >=1000 per cubic millimeter (/mm\^3) (1\*10\^9 per liter \[/L\]).
• Platelet count >= 25,000/mm\^3 (25\*10\^9/L)
• Hemoglobin >= 8 grams per deciliter (g/dL)
• Estimated glomerular filtration rate >= 30 milliliter per minute per 1.73 square meter (mL/min/1.73 m\^2) as assessed by Modification of Diet in Renal Disease (MDRD) formula.
• The participant must have life expectancy of at least 8 weeks.
• The participant has a body weight of at least 35 kilogram (kg).
• The female participant either be of nonchildbearing potential, or if of childbearing potential then have a negative serum human chorionic gonadotropin (hCG) or beta-hCG (β-hCG) pregnancy test at screening. Males, or nonpregnant, nonlactating female participants who are sexually active must agree to comply with the applicable contraceptive requirements of this protocol during the investigational product administration period and for 90 days after the last dose of investigational product.
• The participant must be able to swallow tablets, or receive tablets crushed and/or dispersed in water via a nasogastric or orogastric tube.

Exclusion criteria

• The participant has CMV disease with central nervous system (CNS involvement) (eg, CMV encephalitis) or ophthalmic involvement (eg, CMV retinitis) as assessed by the investigator at the time of screening.
• That participant has uncontrolled other type of infection as assessed by the investigator on the date of treatment assignment.
• The participant has a history of clinically relevant alcohol or drug abuse that may interfere with treatment compliance or assessments with the protocol as determined by the investigator.
• The participant has a known hypersensitivity to maribavir or to any excipients.
• The participant has severe vomiting, diarrhea, or other severe gastrointestinal (GI) illness within 24 hours prior to the first dose of investigational product or a GI absorption abnormality that would preclude administration of oral medication.
• The participant has any clinically significant medical or surgical condition that, in the investigator's opinion, could interfere with interpretation of study results, contraindicate the administration of the investigational product, or compromise the safety or well-being of the participant.
• The participant is receiving valganciclovir, ganciclovir, cidofovir, foscarnet, letermovir, leflunomide, or artesunate when investigational product is initiated, or anticipated to require one of these agents during the 8-week treatment period.
• The participant requires mechanical ventilation or vasopressors for hemodynamic support at the time of baseline.
• The participant has previously received maribavir.
• The participant has previously completed, discontinued, or have been withdrawn from this study.
• The participant has received any investigational agent with known anti-CMV activity within 30 days before initiation of investigational product or CMV vaccine at any time.
• The participant has received any investigational agent or device within 30 days before initiation of investigational product.
• The participant has 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), by a local laboratory. Note: Participants with biopsy confirmed CMV hepatitis will not be excluded from study participation despite AST or ALT >5 times ULN at screening.
• The participant has known (previously documented) positive results for human immunodeficiency virus (HIV). Participant 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.
• The participant has 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 hematopoietic stem-cell transplantation (HSCT) or solid organ transplant (SOT) was performed), as determined by the investigator, are not to be enrolled.
• The participant is undergoing treatment for acute or chronic hepatitis C and hepatitis B.
• The participant is pregnant or expecting to conceive or nursing/breastfeeding.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 12 centers

• Anhui Provincial Hospital(The First Affiliated Hospital of USTC) — Hefei
• Xinqiao Hospital Army Medical University — Chongqing
• Guangzhou First People's Hospital — Guangzhou
• Nanfang Hospital Southern Medical University — Guangzhou
• Henan Cancer Hospital — Zhengzhou
• Union Hospital Tongji Medical College Huazhong University of Science and Technology — Wuhan
• The First Affiliated Hospital of Soochow University — Suzhou
• Peking University People's Hospital — Beijing
• … and 4 more centers

Identifiers

NCT: NCT06439342 · TAK-620-3002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗