Clinical trial NCT05041426: Letermovir for CMV Prevention After Lung Transplantation
Official title: An Open-label Pilot Protocol to Evaluate the Efficacy of Letermovir for the Prevention of Human Cytomegalovirus (CMV) Infection and Disease in Adult Lung Transplant Recipients With Idiopathic Pulmonary Fibrosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Lung Transplant
CMV
Keywords: Lung transplant
CMV
Letermovir
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2021-09-13
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Interventional, open-label, single center, pilot study with historical controls
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Occurrence of CMV infection or disease during prophylaxis
timeFrame: 6-12 months post-transplant
measure: Occurrence of CMV infection or disease in the 3 months following completion of prophylaxis
timeFrame: 12 weeks after completion of letermovir
Secondary outcomes:
measure: Discontinuation events
timeFrame: 6-12 months
measure: Occurrence of leukopenia or neutropenia while on prophylaxis
timeFrame: 6-12 months
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Fernanda Silveira
role: PRINCIPAL_INVESTIGATOR
References: