Fostamatinib for Lung Transplant Rejection

Not yet recruiting at 4 trial locations

Overseen By Sean T Agbor-Enoh, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Must not be taking: Strong CYP3A4 inducers

Disqualifiers: Neutropenia, Hypertension, Hepatitis, Malignancy, HIV, others

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called fostamatinib to determine its effectiveness for individuals who have developed donor-specific antibodies (DSA) after a lung transplant. These antibodies can mistakenly attack the transplanted lung, increasing the risk of rejection and serious complications. Participants will take either the drug or a placebo (a look-alike pill with no medicine) alongside their regular treatment to evaluate the drug's safety. The trial seeks individuals who had their first lung transplant, developed DSA between 21 and 180 days afterward, and can still breathe well without signs of lung rejection. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants will continue with their standard care after a transplant, so it seems likely you can keep taking your usual medications.

Is there any evidence suggesting that fostamatinib is likely to be safe for humans?

Research is investigating the safety of fostamatinib for individuals who have had lung transplants and developed donor-specific antibodies (DSA). These antibodies can cause the body to reject the new lungs. Although detailed safety information for this specific group is not yet available, fostamatinib has been tested in other conditions. It is generally well-tolerated, but like any medication, it can have side effects.

In other studies, some individuals taking fostamatinib experienced side effects such as diarrhea, high blood pressure, and changes in liver enzymes. Doctors will monitor these closely during the trial. It is important to note that this is an early-stage study, meaning researchers are still learning about the drug's safety for this specific use.

Fostamatinib is already approved by the FDA for treating chronic immune thrombocytopenia, a condition characterized by low platelet count. This approval suggests some understanding of its safety. However, its effects and safety in lung transplant patients with DSA are still under investigation. Trial participants will be monitored closely to ensure their safety and to gather more information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Fostamatinib is unique because it offers a different approach for treating lung transplant rejection. Unlike traditional treatments that primarily focus on suppressing the immune system, fostamatinib works by inhibiting the spleen tyrosine kinase (SYK) pathway. This novel mechanism targets immune cells more selectively, potentially reducing the risk of broad immunosuppression and its associated side effects. Researchers are excited about fostamatinib because it may offer a safer, more targeted way to prevent transplant rejection while preserving the body's overall immune function.

What evidence suggests that fostamatinib might be an effective treatment for lung transplant rejection?

Research has shown that fostamatinib may help treat immune-related conditions like chronic immune thrombocytopenia, where the immune system mistakenly attacks blood cells. This drug blocks a protein called Syk, which plays a role in immune responses. In this trial, participants will receive either fostamatinib or a placebo alongside standard care to assess its safety and effectiveness in lung transplant recipients with positive donor-specific antibodies. By targeting Syk, fostamatinib might reduce the body's attack on transplanted lungs, potentially lowering the risk of rejection. Early findings suggest that this approach could improve long-term survival for lung transplant patients who develop donor-specific antibodies. While more research is needed, this method offers hope for those at risk of transplant rejection. ^{1 2 3 4 5}

Who Is on the Research Team?

Sean T Agbor-Enoh, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Are You a Good Fit for This Trial?

This trial is for adults over 18 who have had a lung transplant and then developed donor-specific antibodies, which can lead to organ rejection. Participants will continue their standard post-transplant care.

Inclusion Criteria

Have provided signed written informed consent, prior to performing any study procedure, including screening procedures

First time LT recipients

No prior demonstration of DSA

Exclusion Criteria

Have a significant medical condition that confers an unacceptable risk to participating in the study, and/or that could confound the interpretation of the study data

History of neutropenia, posterior reversible encephalopathy syndrome (PRES), poorly controlled hypertension, positive post-transplant active hepatitis C and/or hepatitis B viral infection, drug-induced cholestatic hepatitis, any primary malignancy, testing positive for human immunodeficiency virus 1 or 2 Ab with evidence for ongoing active infection, current or recent history of psychiatric disorder that could compromise cooperation with study visits and procedures, currently enrolled in another therapeutic clinical trial involving ongoing therapy with any investigational or marketed product or placebo, prior lung or any organ transplant, currently pregnant or lactating, estimated glomerular filtration rate less than 30 mL/min, current or history of grade 3 diarrhea

I am taking medication that strongly affects liver enzyme levels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fostamatinib or placebo, starting with 100 mg orally daily for 2 weeks, then escalating to 100 mg twice daily for 2 weeks, and finally 150 mg twice daily for 4 weeks

8 weeks

Clinic visits every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 follow-up visit

What Are the Treatments Tested in This Trial?

Interventions

• Fostamatinib

Trial Overview The study tests fostamatinib, an oral medication, against a placebo to see if it helps prevent organ rejection in patients with DSA. The treatment lasts for 8 weeks with clinic visits every 2 weeks for monitoring.

How Is the Trial Designed?

Group I: Fostamatinib Experimental Treatment 1 Intervention

Patients will receive fostamatinib with standard of care to assess safety in LT recipients with positive DSA.

Group II: Placebo Placebo Group 1 Intervention

Patients will receive placebo with standard of care to assess safety in LT recipients with positive DSA.

Who Is Running the Clinical Trial?

National Heart, Lung, and Blood Institute (NHLBI)

Lead Sponsor

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Fostamatinib is an effective treatment for chronic immune thrombocytopenia (ITP) in patients who have not responded adequately to at least one prior therapy, as demonstrated in two phase 3 randomized controlled trials (FIT1 and FIT2) across North America, Australia, and Europe.

The drug works by inhibiting spleen tyrosine kinase, which plays a crucial role in the immune response, thereby helping to increase platelet counts in ITP patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fostamatinib for the treatment of chronic immune thrombocytopenia. Connell, NT., Berliner, N.[2021]

Fostamatinib is an oral spleen tyrosine kinase inhibitor that effectively increases platelet counts in adults with immune thrombocytopenia who did not respond adequately to previous treatments, as shown in two Phase III trials.

The treatment is generally well tolerated, with lower rates of severe bleeding-related side effects, although common adverse events include diarrhea, nausea, and liver function test elevations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fostamatinib for the treatment of immune thrombocytopenia in adults. Moore, DC., Gebru, T., Muslimani, A.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06948097?aggFilters=status%3A

Syk Inhibition in MItigating Lung Allograft Rejection ... The overall objective of this study is to assess the clinical safety and tolerability of fostamatinib in lung transplant (LT) patients with positive donor- ...

2. withpower.com withpower.com/trial/phase-1-lung-transplant-4-2025-68395

Fostamatinib for Lung Transplant Rejection Fostamatinib has shown effectiveness in treating immune-related conditions like chronic immune thrombocytopenia (a condition where the immune system attacks ...

3. ctv.veeva.com ctv.veeva.com/study/syk-inhibition-in-mitigating-lung-allograft-rejection-similar-a-trial-to-evaluate-the-safety-and

Syk Inhibition in MItigating Lung Allograft Rejection (SIMILAR) Study Description: The overall objective of this study is to assess the clinical safety and tolerability of fostamatinib in lung transplant (LT) patients with ...

4. app.trialscreen.org app.trialscreen.org/trials/phase-1-syk-inhibition-mitigating-lung-allograft-rejection-similar-to-trial-nct06948097

Syk Inhibition in MItigating Lung Allograft Rejection ... Benefits: Participation in this study may help reduce the risk of lung transplant rejection and improve long-term survival for patients who have developed DSA.

5. clinconnect.io clinconnect.io/trials/NCT06948097

Syk Inhibition in MItigating Lung Allograft Rejection The SIMILAR trial is studying a medication called fostamatinib to see if it can help lung transplant patients who have developed donor-specific antibodies (DSA) ...