Letermovir (Prevymis) for CMV in Kidney and Pancreas Transplant Recipients

An Interventional Study of Letermovir for Secondary Prophylaxis After Treatment of Cytomegalovirus Infection in High Risk (D+/R-) Kidney and Kidney/Pancreas Transplant Recipients

This study is designed to assess how effective letermovir is in preventing recurrence of cytomegalovirus (CMV) infection in adult kidney or kidney/pancreas transplant recipients who are UW Health patients. Participants will be in the study for about 6 months.

Study Overview

• Status: Recruiting
• Conditions: Kidney Transplant Infection; Cytomegalovirus Infections; Pancreas Transplant
• Intervention / Treatment: Drug: Letermovir

Detailed Description

Study Population: Patients over 18 years of age who have undergone kidney or simultaneous kidney/pancreas transplant and are high-risk CMV serostatus (D+/R-) at time of transplant who develop CMV viremia that necessitates treatment per our institutional protocol (enrolled in our CMV stewardship monitoring initiative) and demonstrate proven or presumptive lack of cell-mediated immunity, either by CMI testing or risk factor screening.

Patients will be converted from treatment with ganciclovir derivatives to letermovir (480 mg tablet taken orally once daily) when the viral load via standard of care (SOC) weekly monitoring is < 500 IU/mL. This differs from SOC which only allows conversion to secondary prophylactic treatment after CMV is no longer detected on polymerase chain reaction (PCR) for 2 consecutive weeks. Thus, liberalization of conversion threshold will allow for reduced exposure to valganciclovir via reduced duration of therapy allowing relief of the myelosuppressive toxicity and creates an environment conducive to cell-mediated immunity (CMI).

The primary objective is to assess the efficacy of letermovir as secondary prophylaxis after treatment of CMV infection.

The secondary objective is to detect the development of cytomegalovirus-specific cell-mediated immunity as determined by a positive result using the Eurofins-Viracor CMV inSIGHTTM T Cell Immunity Testing per manufacturer specifications.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sandesh Parajuli, MBBS; Phone Number: (608) 262-2122; Email: sparajuli@medicine.wisc.edu

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • UW Hospital and Clinics
      • Sub-Investigator: Brad Astor, PhD
      • Sub-Investigator: Christopher Saddler, MD
      • Sub-Investigator: Jillian Descourouez, PharmD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• undergone kidney or simultaneous kidney/pancreas transplant
• high-risk CMV serostatus (D+/R-) at time of transplant
• develop CMV viremia that necessitates treatment per our institutional protocol (enrolled in the CMV stewardship monitoring initiative)
• demonstrate proven or presumptive lack of CMI, either by CMI testing or risk factor screening
• able to provide informed consent to participate

Exclusion Criteria:

• contraindication to letermovir or its excipients
• develop ganciclovir-resistant CMV infection
• currently participating in any study involving the administration of a CMV vaccine or another CMV investigational agent
• unable or unwilling, in the opinion of the Investigator, to comply with the protocol
• pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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 for CMV in Transplant Patients; Enrolled participants will be converted from treatment with ganciclovir derivatives to letermovir	Drug: Letermovir; 480 mg taken orally once daily, for 84 days; Other Names: Prevymis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of valganciclovir (VGC) Treatment	To test the hypothesis that letermovir will be associated with reduced duration of (val)ganciclovir treatment, the duration of VGC treatment will be measured.	up to 2 months
Number of distinct episodes of any cytomegalovirus replication greater than 1000 IU/mL	To test the hypothesis that letermovir will be associated with reduced incidence of recurrent viremia, recurrence will be measured defined as incidence of any cytomegalovirus replication greater than 1000 IU/mL requiring treatment after withdrawal of secondary prophylaxis.	up to 90 days after withdrawal of secondary prophylaxis (up to 6 months on study)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Positive Result for T-Cell Immunity Panel (TCIP) Testing	To test the hypothesis that letermovir will be associated with increased development of cytomegalovirus-specific cell-mediated immunity when compared to a literature-based control, development of cytomegalovirus-specific cell-mediated immunity as determined by a positive result using the Eurofins-Viracor CMV inSIGHTTM T-Cell Immunity Testing per manufacturer specifications will be measured. TCIP will be collected from the medical record at these timepoints if possible. Given SOC, access to this test is not always available to all patients at both timepoints.	letermovir initiation (Day 0), at secondary prophylaxis completion (Week 12 +/- 28 days)

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Sandesh Parajuli, MBBS, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: May 6, 2024
• First Submitted That Met QC Criteria: May 6, 2024
• First Posted (Actual): May 9, 2024

Study Record Updates

• Last Update Posted (Estimated): October 8, 2025
• Last Update Submitted That Met QC Criteria: October 6, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Virus Diseases; DNA Virus Infections; Herpesviridae Infections; Cytomegalovirus Infections; Poly(ADP-ribose) Polymerase Inhibitors; Anti-Infective Agents; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antiviral Agents; letermovir
• Other Study ID Numbers: 2024-0174; A561000 (Other Identifier: UW Madison); 235208 (Other Identifier: OnCore ID); Protocol Version 8/22/25 (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes