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

NCT04129398 | Completed Phase 3 Results

• 3 other identifiers: 8228-042MK-8228-042195020
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 4

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.

Conditions

Cytomegalovirus Infection; Cytomegalovirus Disease

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Adverse Events (AEs)

  Percentage of participants with one or more adverse events (AEs)

  Up to week 52 post-transplant

• Percentage of Participants Who Discontinued From Study Drug Due to an AE

  Percentage of participants who discontinued from study drug due to an AE

  Up to week 28 post-transplant

Secondary Outcomes (12)

• Percentage of Participants With Adjudicated CMV Disease or Undergone Anti-CMV Treatment

  Up to Week 52 post-transplant

• Percentage of Participants With Adjudicated CMV Disease

  Up to Week 52 post-transplant

• Percentage of Participants With Quantifiable CMV DNAemia

  Up to Week 52 post-transplant

• Area Under the Concentration-time Curve During a Dosing Interval (AUCtau) of Plasma Letermovir-oral Treatment

  Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose

• Trough Concentration (Ctrough) of Plasma Letermovir - Oral Treatment

  Any day between Days 6-10: 24hrs post-dose

Study Arms (1)

Letermovir

EXPERIMENTAL

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; Drug: Letermovir IV

Interventions

Letermovir tablet DRUG

A single 240 mg tablet or two 240 mg tablets letermovir administered orally, once daily for 28 weeks

Also known as: MK-8228, PREVYMIS®

Letermovir

Letermovir IV DRUG

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

Also known as: MK-8228, PREVYMIS®

Letermovir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 (measured locally).
• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (4)

Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital ( Site 0002)

Nagoya, Aichi-ken, 466-8650, Japan

Location

Sapporo City General Hospital ( Site 0004)

Sapporo, Hokkaido, 060-8604, Japan

Location

Osaka University Hospital ( Site 0003)

Suita, Osaka, 565-0871, Japan

Location

Tokyo Women's Medical University Hospital ( Site 0001)

Tokyo, 162-8666, Japan

Location

Related Publications (1)

• Ishida H, Goto N, Imamura R, Sasaki H, Unagami K, Futamura K, Murata Y, Oshima N, Eto T, Haber B. Letermovir safety and efficacy for cytomegalovirus prophylaxis in adult Japanese kidney transplant recipients: a multicenter, open-label, noncomparative Phase 3 study. Clin Exp Nephrol. 2024 Aug;28(8):822-831. doi: 10.1007/s10157-024-02471-0. Epub 2024 Apr 13.

  PMID: 38615067 RESULT

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Cytomegalovirus Infections

Interventions

letermovir

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2019
• First Posted: October 16, 2019
• Study Start: December 27, 2019
• Primary Completion: October 6, 2022
• Study Completion: October 6, 2022
• Last Updated: August 21, 2024
• Results First Posted: April 1, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share

Locations

JP (4)