Letermovir for CMV Prevention After Lung Transplantation

NCT05041426 | Completed Phase 2 Results FDA Drug

• 1 other identifier: STUDY21040074
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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).

Conditions

Lung Transplant; CMV

Keywords

Lung transplant; CMV; Letermovir

Outcome Measures

Primary Outcomes (2)

• Occurrence of CMV Infection or Disease During Prophylaxis

  Number of lung transplant recipients with idiopathic pulmonary fibrosis with CMV infection or disease during letermovir prophylaxis.

  6-12 months post-transplant

• Occurrence of CMV Infection or Disease in the 3 Months Following Completion of Prophylaxis

  Number of lung transplant recipients with idiopathic pulmonary fibrosis with CMV infection or disease in the 3 months following completion of prophylaxis with letermovir.

  12 weeks after completion of letermovir

Secondary Outcomes (2)

• Discontinuation Events

  6-12 months

• Occurrence of Leukopenia or Neutropenia While on Prophylaxis

  6-12 months

Study Arms (2)

Letermovir

EXPERIMENTAL

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.

Drug: Letermovir

Valganciclovir

ACTIVE COMPARATOR

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-.

Drug: Valganciclovir

Interventions

Letermovir 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.

Also known as: Prevymis

Letermovir

Valganciclovir DRUG

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

Valganciclovir

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fernanda P Silveira, MD, MS: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Interventions

letermovir; Valganciclovir

Intervention Hierarchy (Ancestors)

Ganciclovir; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

The sample size of 15 participants - appropriate for a pilot study and consistent with the study's pre-specified goal - limits statistical power. The open label, single center, single arm design without a concurrent control group precludes definitive conclusions about the efficacy or safety of letermovir in lung transplant recipients relative to valganciclovir.

Results Point of Contact

• Title: Fernanda Silveira, MD, MS, MBA
• Organization: University of Pittsburgh

fps2@pitt.edu

4126486512

Study Officials

• Fernanda Silveira

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Interventional, open-label, single center, pilot study with historical controls

Study Record Dates

• First Submitted: April 20, 2021
• First Posted: September 13, 2021
• Study Start: December 6, 2021
• Primary Completion: March 3, 2025
• Study Completion: March 3, 2025
• Last Updated: April 9, 2026
• Results First Posted: April 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)