Phase IV Study of Maribavir for Reduction of Epstein-Barr Virus Replication in Young Adult Kidney Transplant Recipients

The primary objective is to evaluate the efficacy and safety of maribavir in young adult kidney transplant recipients with persistently high Epstein-Barr virus replication despite standard-of-care therapy. The clinically relevant outcome is eradication of viral replication or a reduction of more than 50% in the high viral load after an initial 6-month treatment course, with extension of therapy in patients showing only partial response.

The secondary objectives are to assess the proportion of patients achieving complete elimination of viral replication during the first study phase and the proportion requiring additional maribavir to obtain a significant reduction in viral replication; the rate of EBV recurrence after treatment withdrawal; the effect of maribavir on EBV-specific T-cell and B-cell immune responses and peripheral blood B-cell subset phenotypes; the kinetics of viral replication during treatment; changes in immunosuppressive therapy during the treatment course; and the frequency and quantity of adverse events potentially related to antiviral therapy.

The sponsor did not provide the study population details because Rowsubjectcount was 0. The trial was described as enrolling young-adult solid organ transplant recipients with a functioning graft and persistently high Epstein-Barr virus replication for more than 2 years, with both males and females aged 18 to 30 years. The total number of participants was stated as 10. Selection was based on the presence of chronic high-level EBV viremia despite standard-of-care therapy, with additional requirements including EBV IgG positivity, CMV PCR negativity, no previous PTLD, and ability to understand and provide informed consent. For female participants of childbearing potential, a negative pregnancy test and use of FDA-approved contraception were required. No lifestyle considerations were provided.

This is a phase IV proof-of-concept, two-step pilot study evaluating the safety and efficacy of maribavir in young adult solid organ transplant recipients with persistently high Epstein-Barr virus replication despite standard-of-care therapy. The planned treatment period consists of an initial 6-month course of maribavir 400 mg twice daily. Participants with a 25% to 50% reduction in viral replication during the first study phase may continue treatment for an additional 3 months. The overall study duration is estimated from February 2026 to November 2027. The study sequence includes a screening visit to assess eligibility criteria, including age, transplant status, Epstein-Barr virus and cytomegalovirus laboratory findings, informed consent, and pregnancy testing where applicable. Follow-up visits are used to assess viral kinetics, safety, efficacy, and immune response during treatment, and an end-of-study visit is performed after completion of treatment or earlier discontinuation. Participant involvement is expected to last up to 9 months, depending on response to the initial treatment phase. Early termination may occur if eligibility criteria are not met, if treatment is stopped according to protocol, or if the participant does not proceed to the additional treatment phase.

The investigational treatment was maribavir, supplied as LIVTENCITY 200 mg film-coated tablets. The planned dose was 400 mg administered orally twice daily. The initial treatment course was 6 months. In participants with a 25% to 50% reduction in viral replication during the first phase, treatment could be continued for an additional 3 months.

The study also included current standard-of-care therapeutic strategies, specified as conversion to mTor-inhibitors, in participants with persistently high Epstein-Barr virus replication despite prior management. No placebo or other comparator treatment was described. Compliance monitoring was not specified in the source data.

Efficacy will be assessed by the proportion of patients achieving complete viral clearance after maribavir therapy. Additional efficacy assessments will include the proportion of patients with complete elimination of viral replication during the first study phase, the proportion of patients requiring an additional maribavir course for a significant reduction of viral replication, the rates of EBV recurrence after maribavir withdrawal, the impact on EBV-specific T- and B-cell immune response after therapy, the impact on B-cell subset phenotypes in peripheral blood, and the kinetics of viral replication over the course of antiviral therapy. The study also aims to evaluate whether the initial 6-month course of maribavir can eradicate or reduce high EBV replication load by more than 50%, with patients showing a 25% to 50% reduction during the first study phase continuing for 3 additional months of therapy.