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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)

Primary Purpose

Cytomegalovirus Infection

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Letermovir
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Cytomegalovirus Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Letermovir

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
February 28, 2023
Last Updated
September 13, 2023
Sponsor
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT05763823
Brief Title
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)
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 24, 2023 (Actual)
Primary Completion Date
May 16, 2024 (Anticipated)
Study Completion Date
May 16, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cytomegalovirus Infection

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Letermovir
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Letermovir
Other Intervention Name(s)
MK-8228
Intervention Description
Letermovir 240 mg or 480 mg oral tablets or IV once daily dose
Primary Outcome Measure Information:
Title
Percentage of Participants With Clinically significant CMV Infection up to Week 24 Post-transplant (~ 6 months)
Description
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.
Time Frame
Up to Week 24 post-transplant (~ 6 months).
Secondary Outcome Measure Information:
Title
Number of Participants Experiencing Adverse Events
Description
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
Time Frame
Up to ~ 24 weeks (~ 6 months) post-transplant
Title
Number of Participants Discontinued From Study Medication Due to an Adverse Event
Description
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.
Time Frame
Up to 14 weeks post-transplant
Title
Percentage of Participants With Clinically-significant CMV Infection up to Week 14 Post-transplant
Description
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.
Time Frame
Up to Week 14 post-transplant.
Title
Percentage of Participants With Pre-emptive Therapy for CMV Viremia up to Week 14 Post-transplant
Description
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.
Time Frame
Up to Week 14 post-transplant
Title
Percentage of Participants With Pre-emptive Therapy for CMV Viremia up to Week 24 Post-transplant
Description
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.
Time Frame
Up to Week 24 post-transplant
Title
Percentage of Participants With CMV End-organ Disease up to Week 14 Post-transplant
Description
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.
Time Frame
Up to Week 14 post-transplant
Title
Percentage of Participants With CMV End-organ Disease up to Week 24 Post-transplant
Description
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.
Time Frame
Up to Week 24 post-transplant
Title
Percentage of Participants With All-cause Mortality up to Week 14 Post-transplant
Description
The percentage of participants who died due to any cause up to week 14 post-transplant will be determined.
Time Frame
Up to Week 14 post-transplant
Title
Percentage of Participants With All-cause Mortality up to Week 24 Post-transplant
Description
The percentage of participants who died due to any cause up to week 24 post-transplant will be determined.
Time Frame
Up to Week 24 post-transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Toll Free Number
Phone
1-888-577-8839
Email
Trialsites@merck.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Anhui Provincial Hospital ( Site 0024)
City
Hefei
State/Province
Anhui
ZIP/Postal Code
230071
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
15255456091
Facility Name
Peking University First Hospital ( Site 0009)
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100034
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+86 18210264969
Facility Name
Peking University People's Hospital-Hematology ( Site 0033)
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100034
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
01088326666
Facility Name
The Second Affiliated Hospital Chongqing Medical University ( Site 0013)
City
Chongqing
State/Province
Chongqing
ZIP/Postal Code
400000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+8613508331213
Facility Name
The Second Affiliated Hospital of Third Military Medical University-Oncology Department ( Site 0002)
City
Chongqing
State/Province
Chongqing
ZIP/Postal Code
400037
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
13228689635
Facility Name
Southwest Hospital of Third Military Medical University ( Site 0005)
City
Chongqing
State/Province
Chongqing
ZIP/Postal Code
400038
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
13650596553
Facility Name
Guangzhou First People's Hospital-Hematology Department ( Site 0001)
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510180
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
86-02081048888
Facility Name
Southern Medical University Nanfang Hospital ( Site 0003)
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510515
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
86-02061641114
Facility Name
Shenzhen Second People's Hospital-Hematology Department ( Site 0006)
City
Shenzhen
State/Province
Guangdong
ZIP/Postal Code
518035
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
86-075583366388
Facility Name
Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 0028)
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430022
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
027-85726114
Facility Name
Tongji Hospital Tongji Medical,Science & Technology ( Site 0032)
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430030
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
027-83665006
Facility Name
The First Affiliated Hospital of Soochow University-hematology department ( Site 0029)
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
8613656214782
Facility Name
The Affiliated Hospital of Xuzhou Medical College ( Site 0022)
City
Xuzhou
State/Province
Jiangsu
ZIP/Postal Code
221006
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
13813282842
Facility Name
The First affiliated hospital of Nanchang University (Xianghu campus) ( Site 0021)
City
Nanchang
State/Province
Jiangxi
ZIP/Postal Code
330209
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
18679119505
Facility Name
The First Hospital of Jilin University-Hematology ( Site 0023)
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130021
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+86 15843073208
Facility Name
The 2nd Affiliated Hospital of Dalian Medical University ( Site 0019)
City
Dalian
State/Province
Liaoning
ZIP/Postal Code
116023
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+86 13909863628
Facility Name
Shanghai General Hospital ( Site 0018)
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200080
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+86 13501672508
Facility Name
West China Hospital, Sichuan University ( Site 0008)
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+8618980601972
Facility Name
The General Hospital of Western Theater Command ( Site 0007)
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610083
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+86 13699418229
Facility Name
Institute of hematology&blood disease hospital-Hematology ( Site 0030)
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
15122538106
Facility Name
The First Affiliated Hospital, Zhejiang University ( Site 0025)
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
8657187236706

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Links:
URL
https://www.merckclinicaltrials.com/
Description
Merck Clinical Trials Information

Learn more about this trial

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)

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