Clinical trial NCT06407232: Letermovir (Prevymis) for CMV in Kidney and Pancreas Transplant Recipients
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Cytomegalovirus Infections
Kidney Transplant Infection
Pancreas Transplant
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2024-05-09
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of distinct episodes of any cytomegalovirus replication greater than 1000 IU/mL
timeFrame: up to 90 days after withdrawal of secondary prophylaxis (up to 6 months on study)
measure: Duration of valganciclovir (VGC) Treatment
timeFrame: up to 2 months
Secondary outcomes:
measure: Number of Participants with Positive Result for T-Cell Immunity Panel (TCIP) Testing
timeFrame: 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)
Other outcomes:
Locations:
city: Madison
country: United States
facility: UW Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Margaret Jorgenson, PharmD, BCTXP
role: PRINCIPAL_INVESTIGATOR
References: