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Letermovir for CMV Prevention After Lung Transplantation

Study Purpose

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).

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT05041426
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Fernanda P Silveira, MD, MS
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Fernanda Silveira
Principal Investigator Affiliation University of Pittsburgh
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Lung Transplant, CMV
Additional Details

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.

Arms & Interventions

Arms

Experimental: 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.

Active Comparator: 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-.

Interventions

Drug: - 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.

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-.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

UPMC, Pittsburgh, Pennsylvania

Status

Not yet recruiting

Address

UPMC

Pittsburgh, Pennsylvania, 15213

Site Contact

Fernanda Silveira, MD

silvfd@upmc.edu

412-648-6512

UPMC, Pittsburgh, Pennsylvania

Status

Recruiting

Address

UPMC

Pittsburgh, Pennsylvania, 15213

Site Contact

Kailey Hughes Kramer, MPH

hugheskl4@upmc.edu

421-648-6453