A Phase 1 Clinical Trial of Siltuximab for the Treatment of Antibody-Mediated Rejection After Lung Transplantation

Launched by WASHINGTON UNIVERSITY SCHOOL OF MEDICINE · May 18, 2025

Keywords

ClinConnect Summary

This clinical trial is looking at a new treatment called Siltuximab for patients who have experienced antibody-mediated rejection after receiving a lung transplant. Antibody-mediated rejection can cause serious problems, including the failure of the transplanted lung. The goal of this study is to see if adding Siltuximab to standard treatments is safe and well-tolerated by patients. If the trial shows that it is safe, future studies will look at how effective it is in treating this condition.

To be eligible for this trial, participants must be at least 18 years old and have recently been diagnosed with antibody-mediated rejection after a lung transplant. They should be in the hospital for treatment and have certain types of antibodies in their blood that indicate rejection. However, there are several reasons someone might not qualify, such as being pregnant, having certain infections, or having undergone recent surgery. Participants in the trial will be closely monitored for safety and any side effects, and they’ll need to provide consent to join. This study is not yet recruiting, so those interested will need to wait until it begins.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. 18 years of age or older,
• • 2. Single or bilateral lung transplant recipient,
• • 3. New diagnosis of clinical definite, probable, or possible antibody-mediated rejection according to the 2016 International Society for Heart and Lung Transplantation (ISHLT) definition with plans to be treated with Carfilzomib and/or anti-thymocyte globulin,
• • 4. Admitted to the hospital for treatment of AMR,
• • 5. Donor-specific antibodies (DSA) to human leukocyte antigens (HLA) with a Mean Fluorescence Intensity (MFI) \> 1000,
• • 6. Able to understand the purpose of the study and willing to participate and sign informed consent.
• Exclusion Criteria:
• • 1. Pregnant or breast feeding,
• • 2. Airway anastomotic dehiscence on bronchoscopy,
• • 3. Thoracotomy incision dehiscence,
• • 4. Underwent lung transplantation less than 6 months before enrollment,
• • 5. Treated with rabbit anti-thymocyte globulin (ATG) for induction immunosuppression at the time of lung transplantation,
• • 6. Underwent other invasive surgical procedure less than 6 weeks before enrollment,
• • 7. History of lymphoma or hematologic malignancy,
• • 8. Treatment with IL-6 signaling blockade with 6 months of enrollment,
• • 9. Planned treatment with plasma exchange (PLEX) for AMR,
• • 10. Cancer other than non-melanoma skin cancer with disease-free period \< 3 years,
• • 11. Positive respiratory virus PCR detected within 7 days of enrollment,
• • 12. Active cytomegalovirus infection within 7 days of enrollment,
• • 13. Positive respiratory culture for Mycobacterium tuberculosis, Mycobacterium abscessus, Mycobacterium chelonae, or Mycobacterium avium complex within 4 weeks of enrollment,
• • 14. Absolute neutrophil count (ANC) \< 1,000 cells/mm3 at enrollment,
• • 15. Platelet count \< 75,000 cells/mm3 at enrollment,
• • 16. Hemoglobin ≥ 17 g/dL at enrollment,
• • 17. ALT or AST \> 2.5 times upper limit of normal at enrollment,
• • 18. Total bilirubin \> 2.5 times upper limit of normal at enrollment,
• • 19. Uric acid ≥ 7 mg/dL at enrollment.
• • 20. History of gastrointestinal tract perforation,
• • 21. History of diverticulitis (diverticulosis is not an exclusion),
• • 22. Plan for surgical procedure (other than bronchoscopy) within 120 days of enrollment.
• • 23. Inability or unwillingness to give written informed consent or comply with the study protocol,
• • 24. Any condition that in the opinion of the site investigator introduces undue risk by participating in this study or impacts the quality or interpretation of the study results.