[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT06990711":3,"trial-entities:NCT06990711":142,"trial-summary:NCT06990711":148},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":20,"study_type":26,"primary_purpose":27,"phases":28,"enrollment_info":30,"interventions":33,"primary_outcomes":46,"secondary_outcomes":51,"sex":87,"minimum_age":88,"maximum_age":89,"healthy_volunteers":90,"eligibility_criteria":91,"std_ages":95,"locations":98,"central_contacts":134,"overall_officials":135,"references":140,"see_also_links":141},"NCT06990711","SILTUX_AMR2025","A Phase 1 Clinical Trial of Siltuximab for the Treatment of Antibody-Mediated Rejection After Lung Transplantation","A Phase 1 Clinical Trial of Siltuximab for the Treatment of Antibody-Mediated Rejection After Lung Transplantation (Siltux-AMR)","RECRUITING","2028-08-31","2026-08","2026-08-27","2025-11-06","Washington University School of Medicine","OTHER",true,"Antibody-mediated rejection after lung transplantation commonly results in allograft failure and death in spite of current therapeutic regimens. We are testing the safety and tolerability of the addition of a novel immunosuppressive medication to routine treatment for antibody-mediated rejection. Future studies will be needed to assess efficacy if this study demonstrates safety","Long-term outcomes after lung transplantation remain disappointing, and the median survival is 6.7 years. Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation. Antibody-mediated rejection (AMR), which is increasingly recognized after lung transplantation, is caused by donor-specific antibodies (DSA) to mismatched human leukocyte antigens (HLA) and frequently results in CLAD and death. Recent multicenter studies using intensive monitoring for AMR report an incidence over 25%. Treatment for AMR has generally focused on antibody depletion and prevention of additional antibody development. Various combinations have been used including high-dose corticosteroids, intravenous immune globulin (IVIG), Rituximab, Carfilzomib, anti-thymocyte globulin (ATG), and plasma exchange (PLEX). However, there have been no randomized controlled trials to guide management, and outcomes after AMR are dismal. One-year allograft survival after AMR is approximately 50%, and 2-year survival is only 20%. IL-6, initially identified as B-cell stimulating factor 2 (BSF-2), is a pleiotropic cytokine that drives deleterious inflammatory, alloimmune, and fibrogenic responses. In conjunction with other cytokines, IL-6 is responsible for normal antibody production and is critical for the induction of follicular helper T cells as well as the production of IL-21 which regulates immunoglobulin synthesis. IL-6 is also crucial for B-cell differentiation into plasmablasts and for enhancing plasmablast survival. These characteristics make IL-6 an especially attractive cytokine to target in the management of AMR. Human studies examining the role of IL-6 signaling blockade in the management of AMR after kidney transplantation have shown promising results, even in refractory cases. Preliminary experience with use of IL-6 signaling blockade in a very small number of lung transplant recipients with AMR has been encouraging. The principal hypothesis for this study is that IL-6 signaling blockade added to routine immunosuppressive treatment for AMR will improve clinical outcomes. However, evaluating the safety of this approach is necessary before examining efficacy in larger clinical trials because infections are the most common serious adverse events associated with IL-6 signaling blockade and a common cause of death at all timepoints after lung transplantation. This study is a Phase 1 clinical trial using Siltuximab, a monoclonal antibody to IL-6, in addition to routine immunosuppressive therapy for AMR to examine safety and define the optimal dose for the treatment of AMR. The primary endpoint is safety and tolerability, and secondary endpoints include pharmacodynamics and functional biological measures relevant to AMR (e.g., DSA, cell-free DNA). Data from this trial will inform the design of a future Phase 2 clinical trial that assesses efficacy. Carefully designed and implemented clinical trials are necessary to improve outcomes after lung transplantation.",[19],"Antibody Mediated Rejection of Lung Transplant",[21,22,23,24,25],"lung transplant","antibody mediated rejection","transplant rejection","IL-6 blockade","donor specific antibodies","INTERVENTIONAL","TREATMENT",[29],"PHASE1",{"count":31,"type":32},30,"ESTIMATED",[34,41],{"type":35,"name":36,"description":37,"armGroupLabels":38},"DRUG","Siltuximab","Interleukin-6 blockade",[39,40],"Siltuximab full-dose (11mg\u002Fkg) IV","Siltuximab half-dose (5.5mg\u002Fkg) IV",{"type":35,"name":42,"description":43,"armGroupLabels":44},"Placebo","Siltuximab placebo IV",[45],"Placebo IV",[47],{"measure":48,"description":49,"timeFrame":50},"Incidence of CTCAE ≥ grade 3","The primary objective is to assess the safety and tolerability of Siltuximab added to routine immunosuppressive treatment for AMR after lung transplantation. The dose of siltuximab (11mg\u002Fkg or 5.5 mg\u002Fkg) with the least side effect profile will be use for future trials of siltuximab in antibody mediated rejection in lung transplantation.","From Randomization to Day 90.",[52,55,59,63,66,70,73,75,78,81,84],{"measure":53,"timeFrame":54},"incidence of CTCAE ≥ grade 3","during a period of 180 days after randomization",{"measure":56,"description":57,"timeFrame":58},"serum high-sensitivity CRP","Pharmacodynamic measure of Il-6 pathway blockade.","Up to 90 and 180 days after randomization",{"measure":60,"description":61,"timeFrame":62},"Blood Sultiximab levels","pharmacokinetic measure","Up to 90 days after randomization",{"measure":64,"timeFrame":65},"Clearance of donor specific antibodies","From randomization to day 180",{"measure":67,"description":68,"timeFrame":69},"Infections","Confirmed bacterial, CMV (defined as a positive blood viral load ≥ 200 IU\u002FmL), mold, mycobacterial, community-acquired respiratory viral infection (each assessed independently), or other opportunistic infection","Between randomization and day 180",{"measure":71,"timeFrame":72},"Change in Forced Vital Capacity (FVC)","between randomization and day 180",{"measure":74,"timeFrame":72},"Change in Forced Expiratory Volume in One Second (FEV1)",{"measure":76,"description":77,"timeFrame":72},"Development of Chronic Lung Allograft Dysfunction","Development of probable CLAD according to the 2019 ISHLT criteria",{"measure":79,"description":80,"timeFrame":72},"Allograft survival","Allograft survival defined as death or undergoing re-transplantation",{"measure":82,"description":83,"timeFrame":72},"Hyperuricemia","Blood uric acid \\> 7 mg\u002FdL",{"measure":85,"description":86,"timeFrame":72},"Hyperlipidemia","Hyperlipidemia requiring the initiation or dose increase of medical therapy","ALL","18 Years",null,false,{"inclusion":92,"exclusion":93,"raw_text":94},[],[],"Inclusion Criteria:\n\n1. 18 years of age or older,\n2. Single or bilateral lung transplant recipient,\n3. 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\u002For anti-thymocyte globulin,\n4. Admitted to the hospital for treatment of AMR,\n5. Donor-specific antibodies (DSA) to human leukocyte antigens (HLA) with a Mean Fluorescence Intensity (MFI) \\> 1000,\n6. Able to understand the purpose of the study and willing to participate and sign informed consent.\n\nExclusion Criteria:\n\n1. Pregnant or breast feeding,\n2. Airway anastomotic dehiscence on bronchoscopy,\n3. Thoracotomy incision dehiscence,\n4. Underwent lung transplantation less than 6 months before enrollment,\n5. Treated with rabbit anti-thymocyte globulin (ATG) for induction immunosuppression at the time of lung transplantation,\n6. Underwent other invasive surgical procedure less than 6 weeks before enrollment,\n7. History of lymphoma or hematologic malignancy,\n8. Treatment with IL-6 signaling blockade with 6 months of enrollment,\n9. Planned treatment with plasma exchange (PLEX) for AMR,\n10. Cancer other than non-melanoma skin cancer with disease-free period \\\u003C 3 years,\n11. Positive respiratory virus PCR detected within 7 days of enrollment,\n12. Active cytomegalovirus infection within 7 days of enrollment,\n13. Positive respiratory culture for Mycobacterium tuberculosis, Mycobacterium abscessus, Mycobacterium chelonae, or Mycobacterium avium complex within 4 weeks of enrollment,\n14. Absolute neutrophil count (ANC) \\\u003C 1,000 cells\u002Fmm3 at enrollment,\n15. Platelet count \\\u003C 75,000 cells\u002Fmm3 at enrollment,\n16. Hemoglobin ≥ 17 g\u002FdL at enrollment,\n17. ALT or AST \\> 2.5 times upper limit of normal at enrollment,\n18. Total bilirubin \\> 2.5 times upper limit of normal at enrollment,\n19. Uric acid ≥ 7 mg\u002FdL at enrollment.\n20. History of gastrointestinal tract perforation,\n21. History of diverticulitis (diverticulosis is not an exclusion),\n22. Plan for surgical procedure (other than bronchoscopy) within 120 days of enrollment.\n23. Inability or unwillingness to give written informed consent or comply with the study protocol,\n24. 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.",[96,97],"ADULT","OLDER_ADULT",[99,120],{"facility":100,"status":8,"city":101,"state":102,"zip":103,"country":104,"contacts":105,"geoPoint":117},"Washington University School, of Medicine, Barnes-Jewish Hospital","St Louis","Missouri","63110","United States",[106,111,115],{"name":107,"role":108,"phone":109,"email":110},"Derek E Byers, MD, PhD","CONTACT","3144548766","dbyers@wustl.edu",{"name":112,"role":108,"phone":113,"email":114},"Brigitte Mittler, CCRC","3147471931","b.mittler@wustl.edu",{"name":107,"role":116},"PRINCIPAL_INVESTIGATOR",{"lat":118,"lon":119},38.62727,-90.19789,{"facility":121,"status":8,"city":122,"state":123,"zip":124,"country":104,"contacts":125},"University of Utah","Saint Lake City","Utah","84112",[126,130],{"name":127,"role":108,"phone":128,"email":129},"Ramsey R Hachem, MD","8015817806","ramsey.hachem@hsc.utah.edu",{"name":131,"role":108,"phone":132,"email":133},"Julia Uddenberg","8016466126","julia.uddenberg@hsc.utah.edu",[],[136,138],{"name":137,"affiliation":121,"role":116},"Ramsey Hachem, MD",{"name":139,"affiliation":13,"role":116},"Derek Byers, MD, PhD",[],[],{"nct_id":4,"conditions":143,"biomarkers":146},[144,145],"Hyperacute graft rejection","Lung Transplantation",[147],"HLA Complex",{"nct_id":4,"found":15,"summary":149,"prompt_version":159},{"design":150,"status":151,"heading":152,"summary":153,"follow_up":154,"word_count":155,"commitments":156,"compensation":157,"drugs_mentioned":158},"This is an interventional study with a planned enrollment of 30 participants. It is testing Siltuximab against a placebo (an inactive substance).","completed","Siltuximab for Antibody-Mediated Rejection After Lung Transplant","This study is testing a new approach for people who have antibody-mediated rejection (AMR) after a lung transplant. AMR is a serious condition where your body's immune system attacks the transplanted lung. We are looking at the safety of adding a medication called Siltuximab to your usual treatment for AMR. Siltuximab works by blocking a protein called Interleukin-6 (IL-6), which plays a role in inflammation and immune responses. This study will enroll 30 participants who are 18 years or older and have a new diagnosis of AMR. The main goal is to see how safe Siltuximab is by tracking any serious side effects for 90 days. If this study shows Siltuximab is safe, future studies will be needed to see how well it works.","The study will track serious side effects for 90 days after randomization.",124,"Not specified in the trial record.","Not stated in the trial record.",[36],"v2"]