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

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

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).

Study Overview

• Status: Recruiting
• Conditions: CMV; Transplant Complication
• Intervention / Treatment: Drug: Valganciclovir; Drug: Maribavir

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Contact: David Taber, PharmD; Phone Number: 843-792-2724; Email: taberd@musc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control; valganciclovir 900mg once daily	Drug: Valganciclovir; valganciclovir 900mg once daily
Experimental: Intervention; maribavir 400mg twice daily	Drug: Maribavir; maribavir 400mg twice daily

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: Takeda

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2023
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): November 30, 2025

Study Registration Dates

• First Submitted: August 29, 2023
• First Submitted That Met QC Criteria: September 5, 2023
• First Posted (Actual): September 13, 2023

Study Record Updates

• Last Update Posted (Estimated): December 6, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiviral Agents; Valganciclovir; Maribavir
• Other Study ID Numbers: Pro00125967

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No