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

Cytomegalovirus Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06407232
• Other study ID #: 2024-0174
• Secondary ID: A561000Protocol
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 2024
• Est. completion date: June 2026

Study information

• Verified date: May 2024
• Source: University of Wisconsin, Madison
• Contact: Margaret Jorgenson, PharmD, BCTXP
• Phone: (608) 262-2122
• Email: mrgebarski[@]wisc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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 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 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 CMI.

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

• Primary hypothesis: letermovir will be associated with reduced duration of (val)ganciclovir treatment and reduced incidence of recurrent viremia.

• Primary endpoint: (val)ganciclovir treatment time will be measured; recurrence will be quantified as number of distinct episodes of any cytomegalovirus replication > 1000 IU/mL after withdrawal of secondary prophylaxis per previous literature.

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.

• Secondary hypothesis: letermovir will be associated with increased development of cytomegalovirus-specific cell-mediated immunity when compared to a literature-based control.

• Secondary endpoint: 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 at the following timepoints: letermovir initiation (Day 0) and monthly through completion of secondary prophylaxis with a minimum requirement of TCIP at secondary prophylaxis completion.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: June 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Cytomegalovirus Infections
• Infections
• Kidney Transplant Infection
• Pancreas Transplant

Intervention

Drug:
• Letermovir
480 mg taken orally once daily, for 84 days

Locations

Country	Name	City	State
United States	UW Hospital and Clinics	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 after withdrawal of secondary prophylaxis.	up to 90 days after withdrawal of secondary prophylaxis (up to 6 months on study)
Primary	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
Secondary	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.	letermovir initiation (Day 0) and monthly through completion of secondary prophylaxis with a minimum requirement of TCIP at secondary prophylaxis completion (Week 12 +/- 28 days)