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

NCT06990711 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: SILTUX_AMR20257R61HL169189-02
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Antibody Mediated Rejection of Lung Transplant

Keywords

lung transplant; antibody mediated rejection; transplant rejection; IL-6 blockade; donor specific antibodies

Outcome Measures

Primary Outcomes (1)

• 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/kg or 5.5 mg/kg) 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.

Secondary Outcomes (11)

• incidence of CTCAE ≥ grade 3

  during a period of 180 days after randomization

• serum high-sensitivity CRP

  Up to 90 and 180 days after randomization

• Blood Sultiximab levels

  Up to 90 days after randomization

• Clearance of donor specific antibodies

  From randomization to day 180

• Infections

  Between randomization and day 180

Other Outcomes (6)

• Donor-derived cell-free DNA < 1%

  up to day 180

• Change in circulating donor-derived cell-free DNA

  up to day 180

• Change in high-sensitivity CRP

  between randomization and day 180

Study Arms (3)

Siltuximab full-dose (11mg/kg) IV

EXPERIMENTAL

Siltuximab 11mg/kg IV on Days 1 and 22

Drug: Siltuximab

Siltuximab half-dose (5.5mg/kg) IV

EXPERIMENTAL

Siltuximab 5.5 mg/kg IV on Days 1 and 22

Drug: Siltuximab

Placebo IV

PLACEBO COMPARATOR

Placebo IV on Days 1 and 22

Drug: Placebo

Interventions

Siltuximab DRUG

Interleukin-6 blockade

Siltuximab full-dose (11mg/kg) IV; Siltuximab half-dose (5.5mg/kg) IV

Placebo DRUG

Siltuximab placebo IV

Placebo IV

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older,
• Single or bilateral lung transplant recipient,
• 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,
• Admitted to the hospital for treatment of AMR,
• Donor-specific antibodies (DSA) to human leukocyte antigens (HLA) with a Mean Fluorescence Intensity (MFI) \> 1000,
• Able to understand the purpose of the study and willing to participate and sign informed consent.

You may not qualify if:

• Pregnant or breast feeding,
• Airway anastomotic dehiscence on bronchoscopy,
• Thoracotomy incision dehiscence,
• Underwent lung transplantation less than 6 months before enrollment,
• Treated with rabbit anti-thymocyte globulin (ATG) for induction immunosuppression at the time of lung transplantation,
• Underwent other invasive surgical procedure less than 6 weeks before enrollment,
• History of lymphoma or hematologic malignancy,
• Treatment with IL-6 signaling blockade with 6 months of enrollment,
• Planned treatment with plasma exchange (PLEX) for AMR,
• Cancer other than non-melanoma skin cancer with disease-free period \< 3 years,
• Positive respiratory virus PCR detected within 7 days of enrollment,
• Active cytomegalovirus infection within 7 days of enrollment,
• Positive respiratory culture for Mycobacterium tuberculosis, Mycobacterium abscessus, Mycobacterium chelonae, or Mycobacterium avium complex within 4 weeks of enrollment,
• Absolute neutrophil count (ANC) \< 1,000 cells/mm3 at enrollment,
• Platelet count \< 75,000 cells/mm3 at enrollment,

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• University of Utah: collaborator

Study Sites (2)

Washington University School, of Medicine, Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

RECRUITING

University of Utah

Saint Lake City, Utah, 84112, United States

RECRUITING

MeSH Terms

Interventions

siltuximab

Study Officials

• Ramsey Hachem, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

• Derek Byers, MD, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Randomized 1:1:1

Study Record Dates

• First Submitted: May 18, 2025
• First Posted: May 25, 2025
• Study Start: November 6, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: December 31, 2025

Record last verified: 2025-12

Locations

US (2)