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)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cytomegalovirus Infection
• Intervention / Treatment: Drug: Letermovir

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@merck.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230071
      • Anhui Provincial Hospital ( Site 0024)
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University First Hospital ( Site 0009)
    • Beijing, Beijing, China, 100034
      • Peking University People's Hospital-Hematology ( Site 0033)
  • Chongqing
    • Chongqing, Chongqing, China, 400037
      • The Second Affiliated Hospital of Third Military Medical University-Oncology Department ( Site 0002)
    • Chongqing, Chongqing, China, 400038
      • Southwest Hospital of Third Military Medical University ( Site 0005)
    • Chongqing, Chongqing, China, 400072
      • The Second Affiliated Hospital Chongqing Medical University ( Site 0013)
  • Guangdong
    • Guangzhou, Guangdong, China, 510180
      • Guangzhou First People's Hospital-Hematology Department ( Site 0001)
    • Guangzhou, Guangdong, China, 510515
      • Southern Medical University Nanfang Hospital ( Site 0003)
    • Shenzhen, Guangdong, China, 518035
      • Shenzhen Second People's Hospital-Hematology Department ( Site 0006)
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 0028)
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital Tongji Medical,Science & Technology ( Site 0032)
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University-hematology department ( Site 0029)
    • Xuzhou, Jiangsu, China, 221006
      • The Affiliated Hospital of Xuzhou Medical College ( Site 0022)
  • Jiangxi
    • Nanchang, Jiangxi, China, 330209
      • The First affiliated hospital of Nanchang University (Xianghu campus) ( Site 0021)
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University-Hematology ( Site 0023)
  • Liaoning
    • Dalian, Liaoning, China, 116023
      • The 2nd Affiliated Hospital of Dalian Medical University ( Site 0019)
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Shanghai General Hospital ( Site 0018)
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University ( Site 0008)
    • Chengdu, Sichuan, China, 610083
      • The General Hospital of Western Theater Command ( Site 0007)
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Institute of hematology&blood disease hospital-Hematology ( Site 0030)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, Zhejiang University ( Site 0025)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Letermovir; Letermovir 240 mg or 480 mg oral tablets or IV once daily dose; Other Names: MK-8228

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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.
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2023
• Primary Completion (Estimated): April 29, 2024
• Study Completion (Estimated): April 29, 2024

Study Registration Dates

• First Submitted: February 28, 2023
• First Submitted That Met QC Criteria: February 28, 2023
• First Posted (Actual): March 10, 2023

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Disease Attributes; DNA Virus Infections; Herpesviridae Infections; Infections; Communicable Diseases; Cytomegalovirus Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Letermovir
• Other Study ID Numbers: 8228-045; MK-8228-045 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No