Syk Inhibition in MItigating Lung Allograft Rejection (SIMILAR): A Phase 1, Double-Blind, Randomized, Placebo-Controlled, Dose Escalation Trial to Evaluate the Safety and Tolerability of Fostamatinib in Lung Transplant Patients With Donor-Specific Antibodies.
National Heart, Lung, and Blood Institute (NHLBI)
Summary
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.
Description
Study Description: The overall objective of this study is to assess the clinical safety and tolerability of fostamatinib in lung transplant (LT) patients with positive donor-specific antibodies (DSA). Subjects who tested positive for DSA will be enrolled. Randomization to fostamatinib or placebo will be blinded. Patients will receive fostamatinib or placebo, first 100 mg orally daily for 2 weeks, then escalate to 100 mg orally twice daily for an additional 2 weeks, and then escalate to 150 mg twice daily for an additional 4 weeks. Subjects will be monitored for 28 additional days. The primary…
Eligibility
- Age range
- 18–99 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: Subjects who do not meet any of the following criteria during screening will not be randomized but will be counted toward study accrual. Screen failures may be rescreened at a later time if the reason for screening failure is revised. In order to be eligible to participate in this study, an individual must meet all of the following criteria: * 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 first test positive for clas…
Interventions
- Drugfostamatinib
The 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.
- DrugPlacebo
Placebo 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.
Locations (5)
- Stanford University School of MedicineStanford, California
- Johns Hopkins University School of MedicineBaltimore, Maryland
- National Heart, Lung and Blood Institute (NHLBI)Bethesda, Maryland
- University of Utah HealthSalt Lake City, Utah
- Inova Health System FoundationFalls Church, Virginia