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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 11
- 主要终点
- Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAE), and Adverse Events of Special interest (AESIs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •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.
研究组 & 干预措施
Maribavir
Participants will receive maribavir 400 milligrams (mg), tablets, orally twice a day (BID) for up to 8 weeks.
干预措施: Maribavir (Drug)
结局指标
主要结局
Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAE), and Adverse Events of Special interest (AESIs)
时间窗: From first dose of study drug up to Week 20
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 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. AESIs is defined as any adverse event of special interest.
Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters
时间窗: From first dose of study drug up to Week 20
Clinical laboratory parameters will include chemistry, hematology, and urinalysis. Any clinical laboratory abnormalities which will be deemed clinically significant by the investigator will be recorded.
Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings
时间窗: From first dose of study drug up to Week 20
12-lead ECG will be evaluated. Any ECG assessments which will be deemed clinically significant by the investigator will be reported.
Number of Participants With Clinically Significant Changes in Vital Signs
时间窗: From first dose of study drug up to Week 20
Vital signs will include temperature, arterial blood pressure (systolic and diastolic) and pulse. Any change in vital signs assessments which will be deemed clinically significant by the investigator will be reported.
Number of Participants Who will Discontinue From the Study Drug and Study
时间窗: From first dose of study drug up to Week 20
Participants discontinuing the study drug treatment and the study will be reported.
次要结局
- 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(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(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 Requiring Alternative Treatment After Achieving CMV Viremia Clearance at Study Week 8(At Week 8)
- Number of Participants With All-cause Mortality During the Study(Up to Week 20)
- Percentage of Participants With Recurrence of CMV Viremia During on Treatment and off Treatment(From first dose of study drug up to Week 8 (on treatment) and Week 20 (off treatment))
- Percentage of Participants With Confirmed Clearance of Plasma CMV Deoxyribose Nucleic Acid (DNA) (CMV Viremia Clearance) at Week 8(At Week 8)
- Percentage of Participants With Achievement of CMV Viremia Clearance and CMV Infection Symptom Control at Weeks 8, 12, 16, and 20(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)(At Week 8)
- Percentage of Participants With Mutations in the CMV Genes Conferring Resistance to Maribavir(Up to Week 20)
- Area Under the Plasma Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration Area (AUC0-t) at Steady State for Maribavir(Week 1, Day 7: Pre-dose, 0.5, 1.5, 3, 4, 6, 8 and 12 hours post-dose)
- Area Under the Plasma Concentration-Time Curve Over 1 Dosing Interval of 12 Hours (AUC0-tau) at Steady State for Maribavir(Week 1, Day 7: Pre-dose, 0.5, 1.5, 3, 4, 6, 8 and 12 hours post-dose)
- Half -life (t1/2) at Steady State for Maribavir(Week 1, Day 7: Pre-dose, 0.5, 1.5, 3, 4, 6, 8 and 12 hours post-dose)
- Maximum Observed Plasma Concentration (Cmax) at Steady State for Maribavir(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(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(Pre-dose and at Weeks 1, 4, and 8)
- Apparent Oral Clearance (CL/F) at Steady State for Maribavir(Week 1, Day 7: Pre-dose, 0.5, 1.5, 3, 4, 6, 8 and 12 hours post-dose)
- Apparent Volume of Distribution (Vz/F) at Steady State for Maribavir(Week 1, Day 7: Pre-dose, 0.5, 1.5, 3, 4, 6, 8 and 12 hours post-dose)
- Terminal Elimination Rate Constant (Lambda z) at Steady State for Maribavir(Week 1, Day 7: Pre-dose, 0.5, 1.5, 3, 4, 6, 8 and 12 hours post-dose)