Maribavir vs. Valganciclovir for CMV Prophylaxis in High-Risk Kidney Transplant Recipients

Study Overview
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Brief Summary
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The purpose of this study is to find out if there is a difference in how well the standard MUSC cytomegalovirus (CMV) prevention medicine works, compared to a different medicine, in preventing CMV infections in kidney transplant recipients who are at risk for this type of infection, while also assessing the tolerability of these two regimens. The two medication regimens being compared are Valganciclovir (FDA approved to prevent and treat CMV infection) vs Maribavir (FDA approved to treat CMV infection) plus Acyclovir (FDA approved to prevent HSV infection).

Detailed Description
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Maribavir has been evaluated for the prevention of CMV infection in Phase II and Phase III trials within allogeneic stem cell transplant recipients. At 6-months post-transplant, the rates of CMV infection using PCR were not different between treatment and placebo arms, although the rates of pp65 antigenemia were lower in the Maribavir group. However, these studies used a low dose of 100mg PO BID. In subsequent studies within solid organ transplantation, Maribavir dosed at 400 to 1200mg PO BID was equally efficacious to valganciclovir for the treatment of CMV infection. Of note and importance to this proposal, the rates of neutropenia were 4-5% in the Maribavir treated patients vs. 15-18% in Valganciclovir patients. Thus, at an appropriate dose, Maribavir appears to have similar efficacy to Valganciclovir in treating CMV infection with a significantly reduced incidence of neutropenia. Currently, there is a lack of randomized controlled trials assessing the safety and efficacy of adequately dosed (=400mg PO BID) Maribavir for the prevention of CMV infection in solid organ transplant recipients. Aim 1. Assess the incidence of leukopenia in those randomized to Maribavir vs. Valganciclovir prophylaxis in adult kidney transplant recipients at high-risk of CMV infection. Hypothesis 1. The incidence of clinically meaningful leukopenia, defined as a WBC count of < 3,000 cells/mm3 and a reduction in total mycophenolate dose below 1,500 mg/day or valganciclovir dose below 900mg per day (adjusted for renal function), will be significantly lower in the Maribavir arm, as compared to the Valganciclovir arm. Aim 2. Assess the efficacy of Maribavir vs. Valganciclovir prophylaxis in adult kidney transplant recipients at high-risk of CMV infection. Hypothesis 2. The incidence of CMV infection and disease will be similar between the Maribavir arm, as compared to the Valganciclovir arm, at 3-, 6-, and 12-months post-transplant. Aim 3. Assess the impact of Maribavir vs. Valganciclovir prophylaxis on healthcare utilization and costs in adult kidney transplant recipients at high-risk of CMV infection. Hypothesis 3. Healthcare utilization will be lower in the Maribavir arm, as compared to the Valganciclovir arm, at 6- and 12-months post-transplant, driven predominantly by reduced number of telephone calls, televisits, and laboratory monitoring encounters. Exploratory Aim 4. Assess the impact of Maribavir vs. Valganciclovir prophylaxis in adult kidney transplant recipients at high-risk of CMV infection on patient-reported outcomes for quality of life and satisfaction. Exploratory Aim 5. Assess any differences in leukopenia, efficacy, healthcare utilization and patient reported outcomes by race and sex in patients randomized to Maribavir vs. Valganciclovir prophylaxis in adult kidney transplant recipients at high-risk of CMV infection.

Official Title
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Randomized Controlled Trial Comparing the Tolerability and Efficacy of Maribavir vs. Valganciclovir for CMV Prophylaxis in High-Risk Kidney Transplant Recipients

Conditions
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Transplant Complication, CMV

Intervention / Treatment
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* Drug: Maribavir
* Drug: Valganciclovir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Kidney transplant recipient at study institution =7 days of transplant Received at least one dose of rATG induction or patient is D+/R- CMV serostatus Exclusion Criteria: Age <18 years at time of transplant Recipient of pancreas, liver, heart, lung transplant Recipient of investigational, non-FDA approved medication

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>valganciclovir 900mg once daily | Drug: Valganciclovir<br>* valganciclovir 900mg once daily<br>|
| Experimental: Intervention<br>maribavir 400mg twice daily | Drug: Maribavir<br>* maribavir 400mg twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the proportion of patients that develop leukopenia in those randomized to maribavir versus those randomized to valganciclovir prophylaxis in adult kidney transplant recipients at high-risk of CMV infection. | Leukopenia is defined as a white blood cell count <3000 cells/mm3 | One year following transplant | 
| Compare the proportion of patients that develop cytomegalovirus (CMV) infection in those randomized to maribavir versus those randomized to valganciclovir prophylaxis in adult kidney transplant recipients at high-risk of CMV infection. | CMV infection is defined as having at least one CMV DNA PCR test of >1000 copies/mL | One year following transplant |