Evaluation of an Immuno-Guided Preventive Strategy Versus Universal Prophylaxis with Valganciclovir for Cytomegalovirus in Kidney Transplant Recipients

The primary objective of this study is to demonstrate the effectiveness of an **immuno-guided** preventive strategy compared to the universal prophylactic strategy in preventing **cytomegalovirus (CMV)** infection within the first 6 months following kidney transplantation in CMV-positive transplant patients. This is clinically relevant as CMV infection is a significant cause of morbidity and mortality in transplant recipients, and optimizing preventive strategies can improve patient outcomes.

Secondary objectives include:

• Demonstrating the efficacy of the immuno-guided strategy in reducing the need for curative treatment of CMV infection within 6 months post-transplantation.
• Assessing the occurrence of CMV disease within 6 months following transplantation.
• Evaluating the prevention of CMV infection at 1 year post-transplantation.
• Comparing the T lymphocyte response at 15 and 28 weeks post-transplant in low- and high-risk patients within the experienced group.
• Comparing the incidence of CMV reactivations based on the donor's serological status at 6 and 12 months post-transplant.
• Conducting a cost-effectiveness analysis of the two strategies to identify costs associated with CMV prevention.

The clinical trial involves a study population of **CMV** seropositive renal transplant patients, aged between 18 and 75 years. Both male and female participants are included, with specific considerations for women of childbearing potential and men regarding contraception during and after the study period. The trial targets individuals who have undergone kidney transplantation within 1 to 12 days prior to enrollment and are receiving non-depleting inducing immunosuppressive treatment. Participants must be affiliated with a social security scheme and have provided informed consent. The trial population is selected based on these criteria, focusing on individuals who are vulnerable due to their recent transplant status and immunosuppressive treatment. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the effectiveness of an **immuno-guided preventive strategy** compared to a universal prophylactic strategy in preventing **cytomegalovirus (CMV)** infection in kidney transplant patients. This is a randomized, double-blind, controlled trial, with an estimated duration from March 2024 to March 2026. The trial will involve adult renal transplant patients aged 18 to 75 years who are CMV seropositive at the time of transplantation. The primary endpoint is the proportion of patients with CMV infection within six months post-transplantation. Secondary endpoints include the need for curative antiviral treatment, the incidence of CMV disease, and the number of CMV-specific T lymphocytes at specified intervals.

Participants will be involved in the study for a maximum of 100 days, with the treatment administered orally in the form of **valganciclovir** film-coated tablets. The study visits will include an initial screening visit to confirm eligibility based on inclusion criteria such as age, CMV seropositivity, and immunosuppressive treatment. Follow-up visits will be scheduled to monitor the patient's health status, CMV infection markers, and any adverse events. The end-of-study visit will assess the final outcomes and collect data on the primary and secondary endpoints.

Participants may be withdrawn from the study if they experience significant adverse effects, fail to comply with the study protocol, or if the investigator deems it necessary for the participant's safety. The trial aims to provide valuable insights into the cost-effectiveness and clinical benefits of the immuno-guided strategy compared to the standard prophylactic approach in managing CMV infection in this patient population.

The clinical trial involves the administration of **Valganciclovir**, marketed under the name **VALGANCICLOVIR VIATRIS 450 mg, comprimé pelliculé**. This experimental medication is presented in the form of a **film-coated tablet**. The active substance, **valganciclovir**, is a mixture and is classified under the ATC code J05AB14. The medication is intended for **oral use**. The maximum daily dose is 900 mg, with a total maximum dose of 90 g over the course of the treatment. The treatment period is capped at 100 days. The pharmaceutical product is not a pediatric formulation and is not classified as an orphan drug. The medication is authorized in France under the marketing authorization number NL 44187.

In addition to the experimental treatment, the study may involve the use of standard-of-care therapy as a comparator treatment. The trial aims to evaluate the effectiveness of an immuno-guided preventive strategy against a universal prophylactic strategy in preventing **cytomegalovirus (CMV) infection** in kidney transplant patients. The study does not include any placebo treatments. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

Efficacy in the clinical trial titled "Effectiveness of a preventive strategy for cytomegalovirus infection guided differently from a universal prophylactic strategy in kidney transplant patients - CYTOPREV" will be assessed using both primary and secondary endpoints. The primary endpoint is the proportion of patients with **cytomegalovirus (CMV) infection** within six months of transplantation. Secondary endpoints include the proportion of patients requiring curative antiviral treatment within six months post-transplantation, the proportion of patients with CMV disease within the same timeframe, and the proportion of patients with CMV infection characterized by CMV DNAemia levels. Additionally, the number of CMV-specific T lymphocytes (IE-1 and pp65) will be measured at weeks 15 and 28. The CMV serological status of the donor will also be evaluated. An incremental cost-effectiveness ratio will be calculated to compare the experimental group with the comparator group, focusing on the cost per CMV infection avoided. These efficacy parameters will be collected and analyzed at specified timepoints to determine the effectiveness of the immuno-guided preventive strategy compared to the universal prophylactic strategy in CMV+ transplant patients.