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

University of Wisconsin (UW)

Status and phase

Enrolling

Phase 3

Conditions

Kidney Transplant Infection

Cytomegalovirus Infections

Pancreas Transplant

Treatments

Drug: Letermovir

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT06407232

2024-0174

Protocol Version 4/24/24 (Other Identifier)

235208 (Other Identifier)

A561000 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

90 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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