Siltuximab for antibody-mediated rejection after lung transplant

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

This study will test whether adding siltuximab, an IL‑6 blocker, to standard treatment is safe and tolerable for adults hospitalized with antibody-mediated rejection after lung transplant.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Washington University School of Medicine (other)
• Drugs / interventions: Rituximab, Siltuximab
• Locations: 2 sites (St Louis, Missouri and 1 other locations)
• Trial ID: NCT06990711 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, inpatient randomized interventional trial adding siltuximab or placebo to routine therapies for antibody‑mediated rejection (AMR) after lung transplantation to characterize safety and tolerability. Eligible participants are adults with a new diagnosis of AMR and donor‑specific HLA antibodies (MFI >1000) who are planned to receive treatments such as carfilzomib or anti‑thymocyte globulin. Participants receive the investigational agent or placebo alongside standard-of-care AMR treatments and are closely monitored for adverse events and immunologic markers. If safety is demonstrated, subsequent studies will be needed to measure efficacy and longer‑term graft outcomes.

Who should consider this trial

Good fit: Adults (≥18) with single or bilateral lung transplants who are hospitalized for a new diagnosis of antibody‑mediated rejection with donor‑specific HLA antibodies (MFI >1000) and planned treatment with carfilzomib and/or anti‑thymocyte globulin are the intended participants.

Not a fit: Patients less than six months post‑transplant, those with airway or incision dehiscence, pregnant or breastfeeding individuals, or those without qualifying donor‑specific antibodies are unlikely to benefit or be eligible for this phase 1 safety study.

Why it matters

Potential benefit: If safe, siltuximab could reduce antibody-driven injury and help preserve lung graft function in patients with AMR.

How similar studies have performed: IL‑6 blockade has shown promise in case series and early reports for antibody‑mediated rejection in other organs (notably kidney), but controlled data in lung transplantation are limited.

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.

Where this trial is running

St Louis, Missouri and 1 other locations

• Washington University School, of Medicine, Barnes-Jewish Hospital — St Louis, Missouri, United States (RECRUITING)
• University of Utah — Saint Lake City, Utah, United States (RECRUITING)

Study contacts

• Principal investigator: Ramsey Hachem, MD — University of Utah

Conditions: Antibody Mediated Rejection of Lung Transplant, lung transplant, antibody mediated rejection, transplant rejection, IL-6 blockade, donor specific antibodies