Letermovir for CMV Prevention After Lung Transplantation

NCT ID: NCT05041426

Last Updated: 2025-07-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-06
• Study Completion Date: 2025-03-03

Brief Summary

This is an interventional, open-label, single center, pilot study with historical controls to test the efficacy of letermovir (LET) for the prevention of CMV infection and disease in adult lung transplant recipients (LTRs) with idiopathic pulmonary fibrosis (IPF).

Detailed Description

Approximately 30 patients with IPF listed for lung transplantation will be enrolled and 15 are expected to undergo lung transplantation during the study period and receive the intervention. Patients who are CMV seropositive will receive letermovir for 6 months, patients who are CMV seronegative and receive lungs from a CMV seropositive donor (CMV D+/R-) will receive letermovir for 12 months. All patients will be followed for 12 weeks after completion of letermovir for the occurrence of CMV infection or disease after prophylaxis.

Historical controls will be LTRs for IPF from 2010-2019 who are CMV R+ or CMV D+/R- (donor positive/recipient negative). CMV prophylaxis in the historical controls was with valganciclovir for 6 months for CMV R+ and for 12 months for CMV D+/R-. Patients will be matched for CMV serostatus, induction immunosuppression, age, and telomere length.

Conditions

Lung Transplant; CMV

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Letermovir

Participants who are CMV seropositive (CMV R+) will receive letermovir prophylaxis for 6 months, and participants who are CMV donor seropositive/recipient seronegative (CMV D+/R-) will receive letermovir prophylaxis for 12 months. Letermovir will be administered at a dose of 480 mg IV or oral once daily. IV administration will occur only for those patients unable to swallow tablets. If letermovir is co-administered with cyclosporine A, the dosage of letermovir will be decreased to 240 mg once daily.

Group Type: EXPERIMENTAL

Letermovir

Intervention Type: DRUG

Participants who are CMV R+ will receive LET prophylaxis for 6 months, and participants who are CMV D+/R- will receive LET prophylaxis for 12 months. The duration of prophylaxis is per current standard of care. LET will be administered at a dose of 480 mg IV or oral once daily. IV administration will occur only for those patients unable to swallow tablets. If LET is co-administered with cyclosporin A (CsA), the dosage of LET should be decreased to 240 mg once daily. All patients will be followed for 12 weeks after completion of LET for the occurrence of CMV infection or disease after prophylaxis. Participants on this protocol will receive acyclovir 400 mg orally BID for the duration of LET therapy for herpes simplex virus and varicella zoster virus prophylaxis.

Valganciclovir

Historical controls will be lung transplant recipients for idiopathic pulmonary fibrosis from 2010-2019 who are CMV R+ or CMV D+/R-. CMV prophylaxis in the historical controls was with valganciclovir for 6 months for CMV R+ and for 12 months for CMV D+/R-.

Group Type: ACTIVE_COMPARATOR

Valganciclovir

Intervention Type: DRUG

Historical controls will have received CMV prophylaxis with valganciclovir for 6 months for CMV R+ and for 12 months for CMV D+/R-.

Interventions

Letermovir

Participants who are CMV R+ will receive LET prophylaxis for 6 months, and participants who are CMV D+/R- will receive LET prophylaxis for 12 months. The duration of prophylaxis is per current standard of care. LET will be administered at a dose of 480 mg IV or oral once daily. IV administration will occur only for those patients unable to swallow tablets. If LET is co-administered with cyclosporin A (CsA), the dosage of LET should be decreased to 240 mg once daily. All patients will be followed for 12 weeks after completion of LET for the occurrence of CMV infection or disease after prophylaxis. Participants on this protocol will receive acyclovir 400 mg orally BID for the duration of LET therapy for herpes simplex virus and varicella zoster virus prophylaxis.

Intervention Type: DRUG

Valganciclovir

Historical controls will have received CMV prophylaxis with valganciclovir for 6 months for CMV R+ and for 12 months for CMV D+/R-.

Intervention Type: DRUG

Other Intervention Names

Prevymis

Eligibility Criteria

Inclusion Criteria

• Age ≥18 years on day of signing informed consent
• Listed for lung transplantation (single or double) due to a diagnosis of IPF or receipt of a lung transplant (single or double) for IPF in the 72 hours prior to enrollment
• Have a documented positive serostatus for CMV (CMV IgG seropositive, R+)
• Have a documented negative serostatus for CMV (CMV IgG seronegative, R-) and anticipate receiving or having received a lung allograft from a CMV IgG positive donor, D+). Only participants who are R+ or who are CMV D+/R- will receive intervention. Participants who are CMV D-/R- will be considered screen failures
• Able to travel to UPMC for routine post-transplant visits for a minimum of 15 months after transplantation
• Able to provide informed consent
• Be willing to use a contraceptive method while receiving LET and for at least 90 days following last dose of LET

Exclusion Criteria

• Receipt of a previous solid organ transplant or hematopoietic stem cell transplant
• Multi-organ transplant recipient, i.e., heart-lung or lung-liver
• HIV seropositive
• HCV antibody or HCV RNA positive
• Donor HCV NAT positive
• Anticipated need for use of ganciclovir, valganciclovir, foscarnet, or cidofovir at the time of transplant
• Known or suspected hypersensitivity to LET or acyclovir
• CrCl < 10 ml/min or dialysis on day of transplant
• Child-Pugh Class C severe hepatic insufficiency
• Pregnancy or expected to conceive while on LET and through at least 90 days following cessation of LET

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Fernanda P Silveira, MD, MS

OTHER

Sponsor Role: lead

Responsible Party

Fernanda P Silveira, MD, MS

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Fernanda Silveira

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

UPMC

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

STUDY21040074

Identifier Type: -

Identifier Source: org_study_id