Efficacy and Safety of Maribavir in HSCT Recipients with Cytomegalovirus Infection Contraindicated for Ganciclovir, Valganciclovir, or Foscarnet

The primary objective is to evaluate the efficacy of maribavir at week 8 in hematopoietic stem cell transplant recipients with cytomegalovirus infection. This assessment applies to patients for whom ganciclovir, valganciclovir, or foscarnet are contraindicated, or those who discontinued these first-line preemptive therapies due to toxicity or intolerance. Additionally, the study aims to assess safety by monitoring adverse events that necessitate treatment discontinuation. Secondary objectives include:

• Evaluation of cytomegalovirus DNAemia recurrence during and up to 8 weeks after the cessation of therapy.
• Assessment of late response in patients demonstrating a partial response at week 8 who extend treatment to a maximum of 12 weeks.
• Evaluation of overall tolerability from the initiation of treatment through 7 days following the final dose.

The sponsor did not provide the total number of participants. The study population consists of adult patients, aged 18 years or older, with both male and female genders. The subjects are recipients of an allogeneic peripheral hematopoietic stem cell transplant performed within the previous twelve months and have been diagnosed with cytomegalovirus infection. Participants must have a body weight of at least 40 kg and an ECOG performance status of less than 3. Inclusion requires the presence of cytomegalovirus infection in individuals who require maribavir as either first-line therapy due to contraindications to ganciclovir, valganciclovir, or foscarnet, or as second-line therapy following the discontinuation of such treatments due to toxicity or intolerance. Eligible subjects must demonstrate adequate renal function with a creatinine clearance of at least 50 ml/min and adequate hepatic function. Exclusion criteria include the presence of active intestinal pathology or diarrhea. Women of childbearing potential are required to utilize highly effective contraception.

This phase 2 multicentric study is designed to evaluate the efficacy and safety of maribavir in recipients of an allogeneic peripheral hematopoietic stem cell transplant diagnosed with cytomegalovirus infection. The investigation focuses on patients for whom ganciclovir, valganciclovir, or foscarnet are contraindicated due to specific medical conditions, or those who have discontinued these first-line therapies due to toxicity or intolerance. The primary efficacy endpoint is the percentage of patients achieving a response, defined as plasma CMV DNA levels below the lower limit of quantification, at 8 weeks of treatment. The primary safety endpoint is the incidence of adverse events requiring treatment discontinuation. Secondary endpoints include the frequency of DNAemia detection during and after treatment, the proportion of late responders, and the incidence of grade > 2 side effects related to the study drug. The study protocol involves a screening process to verify inclusion criteria, such as age over 18 years, adequate renal function, and adequate hepatic function. Participant involvement is centered around the treatment period and subsequent monitoring to assess late responses up to 12 weeks post-therapy. Early termination of maribavir therapy may occur due to adverse side effects.

The investigational medicinal product is maribavir, administered as LIVTENCITY film-coated tablets. The dosage is 800 mg per administration, delivered via the oral route.

The primary efficacy endpoint is the percentage of patients achieving a response to treatment at Study Week 8. A response is defined as a plasma CMV DNA level below the lower limit of quantification, which must be confirmed by at least two consecutive tests. Secondary efficacy assessments include the incidence and frequency of cytomegalovirus DNAemia detection during both the treatment period and the period following treatment discontinuation, up to 8 weeks after the end of maribavir therapy. These data will be evaluated in relation to the risk of cytomegalovirus infection.

A secondary endpoint regarding late response will be evaluated. This is defined as the proportion of patients demonstrating a partial response at 8 weeks of treatment who continue therapy based on investigator judgment and subsequently achieve a response within 12 weeks, characterized by DNAemia below the level of quantification confirmed in at least two consecutive tests.