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MK-8228 (Letermovir) in the Prevention of Human Cytomegalovirus (CMV) Infection and Disease in Adult Japanese Kidney Transplant Recipients (MK-8228-042)

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ClinicalTrials.gov Identifier: NCT04129398
Recruitment Status : Recruiting
First Posted : October 16, 2019
Last Update Posted : June 2, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This study aims to evaluate the safety, efficacy and pharmacokinetics (PK) of Letermovir (LET) administered as prevention of cytomegalovirus (CMV) infection and disease in adult Japanese kidney transplant recipients.

Condition or disease Intervention/treatment Phase
Cytomegalovirus Infection Cytomegalovirus Disease Drug: Letermovir tablet Drug: Letermovir IV Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Phase 3, Open-Label, Single-Arm Clinical Study to Evaluate the Safety, Efficacy and Pharmacokinetics of MK-8228 (Letermovir) for the Prevention of Human Cytomegalovirus (CMV) Infection and Disease in Adult Japanese Kidney Transplant Recipients
Actual Study Start Date : December 27, 2019
Estimated Primary Completion Date : April 15, 2022
Estimated Study Completion Date : April 15, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Letermovir

Arm Intervention/treatment
Experimental: Letermovir
Letermovir oral or intravenous (IV) formulation will be administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose will be 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion will be administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.
Drug: Letermovir tablet
A single 240 mg tablet or two 240 mg tablets letermovir administered orally, once daily for 28 weeks
Other Names:
  • MK-8228
  • PREVYMIS™

Drug: Letermovir IV
IV solution of 240 mg (one vial) or 480 mg (2 vials) letermovir in 250 mL infused over 60 minutes, once daily for 28 weeks
Other Names:
  • MK-8228
  • PREVYMIS™




Primary Outcome Measures :
  1. Percentage of participants with Adverse Events (AEs) [ Time Frame: Up to week 52 post-transplant ]
    Percentage of participants with one or more adverse events (AEs)

  2. Percentage of participants who discontinued from study drug [ Time Frame: Up to week 28 post-transplant ]
    Percentage of participants who discontinued from study drug due to an AE


Secondary Outcome Measures :
  1. Percentage of participants with adjudicated CMV disease or undergone anti-CMV treatment [ Time Frame: Up to Week 52 post-transplant ]
    Percentage of participants with adjudicated CMV disease or undergone anti-CMV treatment

  2. Percentage of participants with adjudicated CMV disease [ Time Frame: Up to Week 52 post-transplant ]
    Percentage of participants with adjudicated CMV disease

  3. Percentage of participants with quantifiable CMV DNAemia [ Time Frame: Up to Week 52 post-transplant ]
    Percentage of participants with quantifiable CMV DNAemia

  4. Area under the concentration-time curve (AUC) of plasma Letermovir - oral treatment [ Time Frame: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose ]
    Area under the concentration-time curve to the end of the dosing period (AUCtau) of plasma LET - oral treatment

  5. Trough concentration (Ctrough) of plasma Letermovir - oral treatment [ Time Frame: Pre-dose on Weeks 1, 2,4, 6, 8, 10, 12, 16, 20, 24 and 28 ]
    Trough concentration (Ctrough) of plasma LET - oral treatment

  6. Maximum concentration (Cmax) of plasma Letermovir - oral treatment [ Time Frame: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose ]
    Maximum concentration (Cmax) of plasma LET - oral treatment

  7. Time to Cmax (Tmax) of plasma Letermovir - oral treatment [ Time Frame: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose ]
    Time to Cmax (Tmax) of plasma LET - oral treatment

  8. Apparent clearance at steady state (CLss/F) of plasma Letermovir - oral treatment [ Time Frame: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose ]
    Apparent clearance at steady state (CLss/F) of plasma LET - oral treatment

  9. Area under the concentration-time curve (AUC) of plasma Letermovir - IV treatment [ Time Frame: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose ]
    Area under the concentration-time curve to the end of the dosing period (AUCtau) of plasma LET - IV treatment

  10. Trough concentration (Ctrough) of plasma Letermovir - IV treatment [ Time Frame: Pre-dose on Weeks 2,4, 6, 8, 10, 12, 16, 20, 24 and 28 ]
    Trough concentration (Ctrough) of plasma LET - IV treatment

  11. Concentration at the end of infusion (Ceoi) of plasma Letermovir - IV treatment [ Time Frame: Any day between Days 6-10: at end of infusion (up to 1 hour) ]
    Concentration at the end of infusion (Ceoi) of plasma LET - IV treatment

  12. Clearance at steady state (CLss) of plasma Letermovir - IV treatment [ Time Frame: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose ]
    Clearance at steady state (CLss) of plasma LET - IV treatment



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Meets recipient and/or donor CMV Immunoglobulin G (IgG) serostatus.
  • Anticipates receiving a primary or secondary allograft kidney at the time of screening and have received a primary or secondary allograft kidney at the time of allocation.
  • Is within 0 (i.e., day of transplantation) to 7 days (inclusive) post-kidney transplant at the time of allocation.
  • Is a Japanese male or female from 18 years to any years of age inclusive, at the time of signing the informed consent.
  • Female is not pregnant or breastfeeding, and is not a woman of childbearing potential (WOCBP); but if a WOCBP, she is using an acceptable contraceptive method, or is abstinent from heterosexual intercourse, and must have a negative highly sensitive pregnancy test within 72 hours before the first dose of study intervention.

Exclusion Criteria:

  • Has received a previous solid organ transplant or hematopoietic stem cell transplant (HSCT).
  • Is a multi-organ transplant recipient (e.g., kidney-pancreas).
  • Has a history of CMV disease or suspected CMV disease within 6 months prior to allocation.
  • Has positive results on CMV assay and/or CMV antigen test at any time between the completion of the transplant surgery and time of allocation.
  • Has suspected or known hypersensitivity to active or inactive ingredients of LET formulations.
  • Is on dialysis (for the purposes of this protocol dialysis includes hemofiltration) or plasmapheresis at the time of allocation.
  • Has Child-Pugh Class C severe hepatic insufficiency at screening.
  • Has post-transplant renal function of creatinine clearance (CrCl) ≤10 mL/min at allocation.
  • Has both moderate hepatic insufficiency AND moderate-to-severe renal insufficiency at screening.
  • Has any uncontrolled infection on the day of allocation.
  • Has documented positive results for human immunodeficiency virus antibody (HIV-Ab) test at any time prior to allocation, or for hepatitis C virus antibody (HCV-Ab) and with detectable HCV RNA within 90 days prior to allocation or hepatitis B surface antigen (HBsAg) within 90 days prior to allocation.
  • Requires mechanical ventilation, or is hemodynamically unstable, at the time of allocation.
  • Has a history of malignancy ≤5 years prior to signing informed consent.
  • Has received within 30 days prior to allocation or plans to receive during the study any of the following: CMV immune globulin; any investigational CMV antiviral agent/biologic therapy.
  • Has received any dose of LET prior to allocation.
  • Has received within 7 days prior to allocation or plans to receive during the study any anti-CMV drug therapy.
  • Is a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence.
  • Is taking or plans to take any of the prohibited medications listed in the protocol.
  • Is currently participating or has participated in a study with an unapproved investigational compound or device within 28 days, or 5× half-life of the investigational compound.
  • Has previously participated in this study or any other study involving LET.
  • Has previously participated or is currently participating in any study involving administration of a CMV vaccine or another CMV investigational agent, or is planning to participate in a study of a CMV vaccine or another CMV investigational agent during the course of this study.
  • Is pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from the time of consent through at least 28 days following cessation of study therapy.
  • Is expecting to donate eggs starting from the time of consent through at least 28 days following cessation of study therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04129398


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
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Japan
Japanese Red Cross Nagoya Daini Hospital ( Site 0002) Recruiting
Nagoya, Aichi, Japan, 466-8650
Contact: Study Coordinator    +81528321121      
Sapporo City General Hospital ( Site 0004) Recruiting
Sapporo, Hokkaido, Japan, 060-8604
Contact: Study Coordinator    +81117262211      
Osaka University Hospital ( Site 0003) Recruiting
Suita, Osaka, Japan, 565-0871
Contact: Study Coordinator    +81668795111      
Tokyo Women's Medical University Hospital ( Site 0001) Recruiting
Tokyo, Japan, 162-8666
Contact: Study Coordinator    +81333538111      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT04129398    
Other Study ID Numbers: 8228-042
MK-8228-042 ( Other Identifier: Merck Protocol Number )
195020 ( Registry Identifier: JAPIC-CTI )
First Posted: October 16, 2019    Key Record Dates
Last Update Posted: June 2, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Cytomegalovirus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases