NCT06334497

Letermovir-based Dual Therapy for Treatment of Cytomegalovirus Infections

Letermovir/Valganciclovir Combination Versus Valganciclovir Monotherapy for Treatment of Cytomegalovirus (CMV) Infections in Kidney Transplant Recipients

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 80 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the efficacy and the tolerance of letermovir as part of dual antiviral therapy (in association with valganciclovir) in renal transplant recipients with CMV DNAemia, requiring valganciclovir treatment per investigator's judgment.

Detailed description

Ganciclovir and valganciclovir are the drugs of choice to treat CMV infections and diseases in immunocompromised patients. However, (val)ganciclovir does not seem to be a panacea and its modest efficacy and dose-limiting toxicities limit effectiveness. More, (val)ganciclovir use may drive development of drug-resistant infections, particularly in immunocompromised patients. An in vitro study suggested additive effects for the combination of letermovir with all approved drugs for treatment or prevention of CMV infections. Investigator's hypothesis is that letermovir plus valganciclovir dual therapy will inhibit CMV replication faster than valganciclovir monotherapy. More, the use of antiviral dual therapy aims to decrease the risk of drug resistance mutations' selection, as previously demonstrated in several other viral infections. In this study, renal transplant recipients with CMV DNAemia requiring valganciclovir will be randomized to receive either letermovir plus valganciclovir or letermovir placebo plus valganciclovir, until reaching the "treatment success" or the "treatment failure" criteria, up to 12 weeks. Treatment success will be defined as, from Week-3: * eradication of CMV DNAemia, defined as CMV DNAemia in whole blood below lower limit of quantification (LLOQ) \< 200 IU/mL on 1 blood sample. * AND resolution of clinical symptoms of CMV disease (if appropriate) Treatment failure will be defined as fulfilling at least one criterion among: * failure to achieve a decrease of CMV DNAemia ≥ 1 log10 IU/mL at Week-3 compared to the baseline CMV DNAemia * persistence of CMV DNAemia ≥ LLOQ (200 IU/ml) at Week-12 * absence of improved CMV disease at Week-3.

Conditions

• Cytomegalovirus Infection

Interventions

Type	Name	Description
DRUG	Letermovir	480mg (2X240mg- tablets) of Letermovir given orally once a day until the "treatment success" or the "treatment failure", up to 12 weeks. In case of co-administration with cyclosporine A, the dosage of Letermovir will be reduced.
DRUG	Valganciclovir	Valganciclovir 900 mg (2X450 mg-tablets) twice a day until the "treatment success" or the "treatment failure", up to 12 weeks. In case of impaired renal function, the dosage of valganciclovir will be reduced.
DRUG	Letermovir placebo	480mg (2X240mg- tablets) of Letermovir placebo given orally once a day until the "treatment success" or the "treatment failure", up to 12 weeks

Timeline

• Start date: 2024-08-14
• Primary completion: 2027-09-01
• Completion: 2027-11-01
• First posted: 2024-03-28
• Last updated: 2026-01-02

Locations

5 sites across 1 country: France