Efficacy and Safety of Immune-Guided Prophylaxis with Ganciclovir and Valganciclovir Hydrochloride in Low-Risk Renal Transplant Recipients

The primary objective of this clinical trial is to compare the **efficacy** and safety of immune-guided prophylaxis versus preemptive therapy in kidney transplant recipients. This is clinically relevant as it aims to optimize the management of cytomegalovirus (CMV) infection in low-risk renal transplant patients, potentially improving patient outcomes and reducing the risk of CMV-related complications.

Secondary objectives include:

• Identifying a subgroup of patients in whom viral monitoring can be avoided, which could streamline patient management and reduce healthcare costs.
• Identifying CMI-seropositive patients with non-protective CMI-CMV to ensure proper prevention, enhancing targeted prophylactic strategies.
• Comparing valganciclovir consumption between both groups and analyzing the development of neutropenia, which could inform dosing strategies and minimize adverse effects.
• Identifying antiviral resistance through mutation studies in the involved genes (UL97, UL54), Sanger sequencing, and next-generation sequencing (NGS) in patients with refractory replication, which is crucial for tailoring antiviral therapy.
• Studying the differences in efficacy and safety of immune-guided prophylaxis based on the recipient's sex, which could lead to personalized treatment approaches.

The clinical trial involves **low-risk renal transplant patients** with the primary objective of comparing the efficacy and safety of immune-guided prophylaxis versus preemptive therapy in kidney transplant recipients. The study population includes both male and female participants who are over 18 years of age and are **CMV-seropositive kidney transplant recipients**. Non-menopausal women must have a negative pregnancy test to be eligible. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity. Participants were selected based on their health status as kidney transplant recipients, and the trial does not focus on any particular lifestyle habits.

The clinical trial is designed to evaluate the **efficacy** and safety of immune-guided prophylaxis compared to preemptive therapy in kidney transplant recipients. This study is a randomized, double-blind, controlled trial involving low-risk renal transplant patients. The trial is expected to commence recruitment on September 8, 2025, and conclude by September 8, 2029. Participants will be randomly assigned to receive either **ganciclovir** or **valganciclovir hydrochloride**. The trial will assess the primary endpoints of efficacy, measured by the incidence of **CMV disease** at 6 and 12 months post-transplant, and safety, evaluated by the proportion of patients experiencing neutropenia at the same intervals.

The study will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits at 6 and 12 months post-transplant to monitor efficacy and safety outcomes, and an end-of-study visit to conclude participation. The inclusion criteria require participants to be over 18 years of age, **CMV-seropositive**, and, for non-menopausal women, to have a negative pregnancy test. The expected duration of participant involvement is up to 52 weeks, with conditions for early termination including significant adverse events or withdrawal of consent.

Secondary endpoints will focus on safety, including the number of days on **valganciclovir** and the frequency of adverse events occurring in more than 10% of participants at 6 months post-transplant. Additionally, a combination of **CMV disease** and neutropenia will be assessed using the Desirability of Outcome Ranking (DOOR) method, which ranks patient outcomes to estimate the probability of a better result in one group. A probability greater than 50%, with 95% confidence intervals excluding 50%, will indicate a significantly better outcome. The trial is categorized as a Phase III study, with a low-intervention classification, ensuring a rigorous evaluation of the therapeutic strategies under investigation.

The clinical trial involves the administration of **Ganciclovir Accord**, a pharmaceutical product formulated as a **solution for infusion**. This experimental medication is provided as a powder for concentrate, which is reconstituted to form a solution for intravenous infusion. The active substance in this formulation is **ganciclovir**, a chemical compound classified under the ATC code J05AB06. The maximum daily dose is 10 mg/kg, with a total treatment period not exceeding 3 weeks. The administration route is via infusion, and the product is manufactured by Accord Healthcare S.L.U. Compliance with the dosing schedule is monitored through regular assessments to ensure adherence to the prescribed regimen.

Additionally, the trial includes the use of **Valganciclovir Normon**, which is provided in the form of **film-coated tablets**. The active ingredient in this medication is **valganciclovir hydrochloride**, a chemical derivative of ganciclovir, classified under the ATC code J05AB14. The maximum daily dose for this oral formulation is 900 mg, with a treatment duration extending up to 52 weeks. The tablets are administered orally, and the product is manufactured by Laboratorios Normon, S.A. Participant compliance is monitored through pill counts and patient diaries to ensure accurate adherence to the dosing schedule.

Both medications are categorized as antivirals and are utilized in the context of the trial to evaluate their efficacy and safety in the prevention of **cytomegalovirus (CMV) infection** in low-risk kidney transplant recipients. The trial aims to compare immune-guided prophylaxis with preemptive therapy, with careful monitoring of participant compliance and response to treatment.

The efficacy of the clinical trial titled "Efficacy and Safety Clinical Trial for Immune-Guided Prevention of **CMV** Infection in Low-Risk Kidney Transplantation" will be assessed using specific primary and secondary endpoints. The primary efficacy endpoint is the proportion of patients with **CMV** disease (incidence) at 6 and 12 months after transplantation. This will be measured to determine the effectiveness of immune-guided prophylaxis compared to preemptive therapy in preventing **CMV** infection in kidney transplant recipients.

Secondary endpoints include a combination of efficacy and safety measures. The **CMV** disease/neutropenia combination will be assessed at 6 and 12 months using the Desirability of Outcome Ranking (DOOR) method. The DOOR method ranks patient outcomes, with the best outcome being no **CMV** disease/replication without neutropenia (<1500 mm³), and the worst being **CMV** disease/replication with neutropenia. The probability of a better result in one group is estimated, with a probability greater than 50% and 95% confidence intervals excluding 50% indicating a significantly better outcome.