A Study of Letermovir (MK-8228) to Evaluate Efficacy and Safety for Prevention of CMV Infection in Chinese Hematopoietic Stem Cell Transplant Recipients (MK-8228-045)
- Registration Number
- NCT05763823
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to evaluate the efficacy and safety of once-a-day orally or IV dose of Letermovir (MK-8228) in Chinese adult Hematopoietic Stem Cell Transplant (HSCT) recipients for the prevention of clinically significant Cytomegalovirus (CMV) Infection.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 120
- Male/Female Chinese adult participant of an allogeneic Hematopoietic Stem Cell Transplant (HSCT).
- Has documented positive Cytomegalovirus (CMV) serostatus (CMV immunoglobulin G [IgG] seropositive) for recipient (R+) at the time of screening.
- Is receiving a first allogeneic HSCT.
- Is within 28 days post-HSCT at the time of randomization.
- Female participant is not a Woman of Child Bearing Potential (WOCBP) or is a WOBCP who agrees to use acceptable contraception during the treatment period and for β₯28 days after the last dose of study drug.
- Received a previous allogeneic HSCT.
- Has a history of CMV end-organ disease within 6 months prior to randomization.
- Has evidence of CMV viremia at any time from HSCT procedure until the time of randomization.
- Has severe hepatic insufficiency.
- Is a) on renal replacement therapy (e.g., hemodialysis, peritoneal dialysis) OR b) has end stage renal impairment with a creatinine clearance <=10 mL/min within 5 days prior to randomization.
- Has both moderate hepatic insufficiency AND moderate to severe renal insufficiency.
- Has an uncontrolled infection on the day of randomization.
- Has rapidly progressing disease that requires mechanical ventilation or is hemodynamically unstable.
- Has a documented positive result for a human immunodeficiency virus antibody (HIV-Ab) test at any time prior to randomization, or for hepatitis C virus antibody (HCV-Ab) with detectable HCV ribonucleic acid (RNA), or hepatitis B surface antigen (HBsAg) within 90 days prior to randomization.
- Has active solid tumor malignancies except localized basal cell or squamous cell skin cancer or the condition under treatment (e.g., lymphomas).
- Has received any prohibited medications within 2 days prior to initiation of treatment with Letermovir.
- Is anticipated to be treated with Traditional Chinese Medicine or herbal medicine during the study treatment period and for 14 days after study medication.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Letermovir Letermovir Chinese HSCT recipients will receive 240 mg \[for participants on Cyclosporin A (CsA)\] or 480 mg (for participants not on CsA) Letermovir orally or IV once daily through week 14 (\~100 days) post-transplant.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Clinically significant CMV Infection up to Week 24 Post-transplant (~ 6 months) Up to Week 24 post-transplant (~ 6 months). Clinically significant CMV infection was defined as either one of the following: 1) initiation of anti-CMV pre-emptive therapy based on documented CMV viremia and the clinical condition of the participant or 2) onset of CMV end-organ disease. The percentage of participants with clinically significant CMV infection will be assessed.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Clinically-significant CMV Infection up to Week 14 Post-transplant Up to Week 14 post-transplant. Clinically significant CMV infection was defined as either one of the following: 1) initiation of anti-CMV pre-emptive therapy based on documented CMV viremia and the clinical condition of the participant or 2) onset of CMV end-organ disease. The percentage of participants with clinically significant CMV infection will be assessed.
Percentage of Participants With CMV End-organ Disease up to Week 14 Post-transplant Up to Week 14 post-transplant CMV end-organ disease met per-protocol diagnostic criteria for CMV-pneumonia, gastrointestinal disease, hepatitis, central nervous system disease, retinitis, nephritis, cystitis, myocarditis, pancreatitis, or other disease categories. Only Clinical Adjudication Committee-confirmed CMV end-organ disease will be included in this analysis. The percentage of participants with CMV end-organ disease will be assessed.
Percentage of Participants With Pre-emptive Therapy for CMV Viremia up to Week 14 Post-transplant Up to Week 14 post-transplant Initiation of anti-CMV pre-emptive therapy was based on documented CMV viremia and the clinical condition of the participant. The percentage of participants with initiation of anti-CMV pre-emptive anti-CMV therapy will be assessed.
Number of Participants Experiencing Adverse Events Up to ~ 24 weeks (~ 6 months) post-transplant An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention
Number of Participants Discontinued From Study Medication Due to an Adverse Event Up to 14 weeks post-transplant An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be assessed.
Percentage of Participants With Pre-emptive Therapy for CMV Viremia up to Week 24 Post-transplant Up to Week 24 post-transplant Initiation of anti-CMV pre-emptive therapy was based on documented CMV viremia and the clinical condition of the participant. The percentage of participants with initiation of anti-CMV pre-emptive anti-CMV therapy will be assessed.
Percentage of Participants With CMV End-organ Disease up to Week 24 Post-transplant Up to Week 24 post-transplant CMV end-organ disease met per-protocol diagnostic criteria for CMV-pneumonia, gastrointestinal disease, hepatitis, central nervous system disease, retinitis, nephritis, cystitis, myocarditis, pancreatitis, or other disease categories. Only Clinical Adjudication Committee-confirmed CMV end-organ disease will be included in this analysis. The percentage of participants with CMV end-organ disease will be assessed.
Percentage of Participants With All-cause Mortality up to Week 14 Post-transplant Up to Week 14 post-transplant The percentage of participants who died due to any cause up to week 14 post-transplant will be determined.
Percentage of Participants With All-cause Mortality up to Week 24 Post-transplant Up to Week 24 post-transplant The percentage of participants who died due to any cause up to week 24 post-transplant will be determined.
Trial Locations
- Locations (21)
Institute of hematology&blood disease hospital-Hematology ( Site 0030)
π¨π³Tianjin, Tianjin, China
Shenzhen Second People's Hospital-Hematology Department ( Site 0006)
π¨π³Shenzhen, Guangdong, China
The First Affiliated Hospital of Soochow University-hematology department ( Site 0029)
π¨π³Suzhou, Jiangsu, China
The First Hospital of Jilin University-Hematology ( Site 0023)
π¨π³Changchun, Jilin, China
The First affiliated hospital of Nanchang University (Xianghu campus) ( Site 0021)
π¨π³Nanchang, Jiangxi, China
The General Hospital of Western Theater Command ( Site 0007)
π¨π³Chengdu, Sichuan, China
Tongji Hospital Tongji Medical,Science & Technology ( Site 0032)
π¨π³Wuhan, Hubei, China
The Affiliated Hospital of Xuzhou Medical College ( Site 0022)
π¨π³Xuzhou, Jiangsu, China
The 2nd Affiliated Hospital of Dalian Medical University ( Site 0019)
π¨π³Dalian, Liaoning, China
Shanghai General Hospital ( Site 0018)
π¨π³Shanghai, Shanghai, China
West China Hospital, Sichuan University ( Site 0008)
π¨π³Chengdu, Sichuan, China
The First Affiliated Hospital, Zhejiang University ( Site 0025)
π¨π³Hangzhou, Zhejiang, China
Anhui Provincial Hospital ( Site 0024)
π¨π³Hefei, Anhui, China
Peking University People's Hospital-Hematology ( Site 0033)
π¨π³Beijing, Beijing, China
Peking University First Hospital ( Site 0009)
π¨π³Beijing, Beijing, China
The Second Affiliated Hospital of Third Military Medical University-Oncology Department ( Site 0002)
π¨π³Chongqing, Chongqing, China
The Second Affiliated Hospital Chongqing Medical University ( Site 0013)
π¨π³Chongqing, Chongqing, China
Southwest Hospital of Third Military Medical University ( Site 0005)
π¨π³Chongqing, Chongqing, China
Guangzhou First People's Hospital-Hematology Department ( Site 0001)
π¨π³Guangzhou, Guangdong, China
Southern Medical University Nanfang Hospital ( Site 0003)
π¨π³Guangzhou, Guangdong, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 0028)
π¨π³Wuhan, Hubei, China