Background:
People who have lung transplants often survive 6 or 7 years. But some people develop donor-specific antibodies (DSA) after their transplants; antibodies are proteins that attack foreign invaders in the body. Antibodies typically kill viruses and other agents that can cause disease. But when the antibodies attack a transplanted organ, they can cause the body to reject the new tissues. People who develop DSA after a transplant have a higher risk of death within 1 year.
Objective:
To test a drug called fostamatinib in people who develop DSA after a lung transplant.
Eligibility:
Adults aged 18 and older who developed DSA after a lung transplant.
Design:
Participants will continue with their standard care after a transplant.
Fostamatinib is a pill taken by mouth. Some participants will take the study drug along with their standard care; others will take a placebo. A placebo is a pill that looks just like the real drug but contains no medicine. All participants will take 1 pill per day for 2 weeks. Then they will take 2 pills per day for the next 6 weeks.
Participants will have clinic visits every 2 weeks while taking their pills. They will have a physical exam, with blood and urine tests, during each visit.
If participants have fluid samples collected from their airways during their standard treatment, some extra fluid may be collected for this study.
Participants will have a follow-up visit 4 weeks after they stop taking their pills.
First time LT recipients
Have provided signed written informed consent, prior to performing any study procedure, including screening procedures.
Age greater than or equal to 18 years
Patients who are DSA positive after day 21 post-transplantation.
Active CMV, EBV or other opportunistic infections
History of neutropenia (benign ethnic neutropenia and/or acquired neutropenia) within 90 days of screening.
History of posterior reversible encephalopathy syndrome (PRES)
History of poorly controlled hypertension or hypertensive crises (defined as systolic blood pressure >=180 mmHg or average diastolic blood pressure >=120 mmHg based on an average of 3 blood pressure readings despite adequate antihypertensive therapy) unless controlled for >90 days at the time of randomization.
Parallel
fostamatinib
DrugThe study intervention is fostamatinib, administered orally starting at 100 mg daily for 14 days, escalating to 100 mg BID for 14 days, then 150 mg BID for 28 days, based on tolerability. Patients will be monitored for 28 additional days and randomized to receive either fostamatinib or placebo, along with standard of care.
Placebo
DrugPlacebo tablets will match fostamatinib, starting at 100 mg daily for 14 days, escalating to 100 mg BID for 14 days, and then 150 mg BID for 28 days, based on tolerability. Patients will be monitored for an additional 28 days.
Study Drug Discontinuation Rate.
The primary outcome is the number of participants who discontinue the study drug due to adverse events, intolerance, or other reasons during the treatment period.
Safety and AMR Prevention in DSA+ LT Patients.
Secondary outcomes will evaluate additional safety parameters and explore the clinical and molecular benefits of fostamatinib in preventing antibody-mediated rejection (AMR) in DSA+ LT patients.
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