Syk Inhibition in MItigating Lung Allograft Rejection (SIMILAR): A Trial to Evaluate the Safety and Tolerability of Fostamatinib in Lung Transplant Patients With Donor-Specific Antibodies
- Registration Number
- NCT06948097
- Brief 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.
- Detailed 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 outcome is the number of discontinuations of study drug. Secondary outcomes will evaluate other safety parameters, as well as potential clinical and molecular benefits of fostamatinib in the prevention of antibody-mediated rejection (AMR) in DSA+ LT patients.
Objectives:
Primary Objective:
To assess the clinical safety and tolerability of fostamatinib compared to placebo in DSA+ LT patients.
Secondary Objectives:
To evaluate molecular and clinical benefit of fostamatinib compared to placebo in DSA+ LT patients.
Exploratory Objective:
To gain additional molecular insight into the mechanism of fostamatinib in DSA+ LT patients.
Endpoints:
Primary Endpoint:
-Incidence and relationship to study drug of the following: hypertension, neutropenia, diarrhea, increase LFTs requiring discontinuation of study drug.
Secondary Endpoints:
* Rate of DSA clearance
* Relative change of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) from baseline to Day 56 and from baseline to Day 84
* Number of patients who has discontinued the study drug or placebo without restarting by the end of each dose (Day 14, 28, 56) due to serious adverse events
* Incidence of clinical AMR
* Number of temporal holds of study drug at different study drug dose.
* Number of patients with missed doses of study drug at each study visit.
* Number of doses missed at each study drug dose level.
* Total number of drug dose by day 56.
Exploratory Endpoints:
* Adverse events not specified in primary or secondary endpoints: incidence, severity and relationship to study drug
* Bronchoalveolar lavage (BAL) neutrophil extracellular trap (NET) production
* Plasma tissue-specific cell free (cf)DNA levels at baseline, Day 14, Day 28, Day 42, Day 56, Day 84
* Measure blood concentration of fostamatinib at each dose. This will be measured at the end of the study to prevent unblinding.
* Relative change of molecular markers (NETs, interleukin 6, double stranded \[dd\]cfDNA) at baseline, Day 14, Day 28, Day 42, Day 56, and Day 84.
* Rate of DSA clearance, relative change of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) from baseline to Day 56 and from baseline to Day 84.
* Differential gene expression from RNA sequencing of BAL fluid and PBMCs for drug and placebo
* Cf DNA, cytokine, and NET at the time of clinical complication
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Fostamatinib fostamatinib Patients will receive fostamatinib with standard of care to assess safety in LT recipients with positive DSA. Placebo Placebo Patients will receive placebo with standard of care to assess safety in LT recipients with positive DSA.
- Primary Outcome Measures
Name Time Method Study Drug Discontinuation Rate. 12 weeks 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.
- Secondary Outcome Measures
Name Time Method Safety and AMR Prevention in DSA+ LT Patients. 12 weeks 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.
Trial Locations
- Locations (2)
Johns Hopkins University School of Medicine
🇺🇸Baltimore, Maryland, United States
Inova Health System Foundation
🇺🇸Falls Church, Virginia, United States