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)

Cytomegalovirus Infection Clinical Trial

Official title:

A Phase 3, Open Label, Single-Arm Clinical Trial to Evaluate the Efficacy and Safety of MK-8228 (Letermovir) for the Prevention of Clinically Significant Cytomegalovirus (CMV) Infection in Chinese Adult, CMV-Seropositive Allogeneic Hematopoietic Stem Cell Transplant Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05763823
• Other study ID #: 8228-045
• Secondary ID: MK-8228-045
• Status: Completed
• Phase: Phase 3
• Start date: March 24, 2023
• Est. completion date: April 18, 2024

Study information

• Verified date: April 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: April 18, 2024
• Est. primary completion date: April 18, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

The key inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

• 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 =28 days after the last dose of study drug.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Communicable Diseases
• Cytomegalovirus Infection
• Cytomegalovirus Infections
• Infections

Intervention

Drug:
• Letermovir
Letermovir 240 mg or 480 mg oral tablets or IV once daily dose

Locations

Country	Name	City	State
China	Peking University First Hospital ( Site 0009)	Beijing	Beijing
China	Peking University People's Hospital-Hematology ( Site 0033)	Beijing	Beijing
China	The First Hospital of Jilin University-Hematology ( Site 0023)	Changchun	Jilin
China	The General Hospital of Western Theater Command ( Site 0007)	Chengdu	Sichuan
China	West China Hospital, Sichuan University ( Site 0008)	Chengdu	Sichuan
China	Southwest Hospital of Third Military Medical University ( Site 0005)	Chongqing	Chongqing
China	The Second Affiliated Hospital Chongqing Medical University ( Site 0013)	Chongqing	Chongqing
China	The Second Affiliated Hospital of Third Military Medical University-Oncology Department ( Site 0002)	Chongqing	Chongqing
China	The 2nd Affiliated Hospital of Dalian Medical University ( Site 0019)	Dalian	Liaoning
China	Guangzhou First People's Hospital-Hematology Department ( Site 0001)	Guangzhou	Guangdong
China	Southern Medical University Nanfang Hospital ( Site 0003)	Guangzhou	Guangdong
China	The First Affiliated Hospital, Zhejiang University ( Site 0025)	Hangzhou	Zhejiang
China	Anhui Provincial Hospital ( Site 0024)	Hefei	Anhui
China	The First affiliated hospital of Nanchang University (Xianghu campus) ( Site 0021)	Nanchang	Jiangxi
China	Shanghai General Hospital ( Site 0018)	Shanghai	Shanghai
China	Shenzhen Second People's Hospital-Hematology Department ( Site 0006)	Shenzhen	Guangdong
China	The First Affiliated Hospital of Soochow University-hematology department ( Site 0029)	Suzhou	Jiangsu
China	Institute of hematology&blood disease hospital-Hematology ( Site 0030)	Tianjin	Tianjin
China	Tongji Hospital Tongji Medical,Science & Technology ( Site 0032)	Wuhan	Hubei
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 0028)	Wuhan	Hubei
China	The Affiliated Hospital of Xuzhou Medical College ( Site 0022)	Xuzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Clinically significant CMV Infection 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.	Up to Week 24 post-transplant (~ 6 months).
Secondary	Number of Participants Experiencing Adverse Events	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	Up to ~ 24 weeks (~ 6 months) post-transplant
Secondary	Number of Participants Discontinued From Study Medication Due to an Adverse Event	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.	Up to 14 weeks post-transplant
Secondary	Percentage of Participants With Clinically-significant CMV Infection 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.	Up to Week 14 post-transplant.
Secondary	Percentage of Participants With Pre-emptive Therapy for CMV Viremia 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.	Up to Week 14 post-transplant
Secondary	Percentage of Participants With Pre-emptive Therapy for CMV Viremia 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.	Up to Week 24 post-transplant
Secondary	Percentage of Participants With CMV End-organ Disease 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.	Up to Week 14 post-transplant
Secondary	Percentage of Participants With CMV End-organ Disease 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.	Up to Week 24 post-transplant
Secondary	Percentage of Participants With All-cause Mortality 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.	Up to Week 14 post-transplant
Secondary	Percentage of Participants With All-cause Mortality 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.	Up to Week 24 post-transplant

External Links

•   Merck Clinical Trials Information