Fostamatinib for Lung Transplant Rejection

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

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug 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 platelets) and rheumatoid arthritis (a condition causing joint inflammation), suggesting it may help with immune responses involved in lung 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 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]

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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Fostamatinib for the treatment of immune thrombocytopenia in adults. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Fostamatinib for the treatment of chronic immune thrombocytopenia. [2021]

3. England pubmed.ncbi.nlm.nih.gov

A phase II trial to evaluate the efficacy of fostamatinib in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). [2022]

4. Canada pubmed.ncbi.nlm.nih.gov

A phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study of 2 dosing regimens of fostamatinib in patients with rheumatoid arthritis with an inadequate response to a tumor necrosis factor-α antagonist. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

An oral Syk kinase inhibitor in the treatment of rheumatoid arthritis: a three-month randomized, placebo-controlled, phase II study in patients with active rheumatoid arthritis that did not respond to biologic agents. [2021]