Antibody Mediated Rejection of Lung TransplantPhase 1Siltux-AMRNCT06990711
A Phase 1 Clinical Trial of Siltuximab for the Treatment of Antibody-Mediated Rejection After Lung Transplantation
A Phase 1 study testing Siltuximab in people with Antibody Mediated Rejection of Lung Transplant, run by Washington University School of Medicine at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Antibody Mediated Rejection of Lung Transplant
- What is being tested?
- Siltuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 2 sitesUnited States
- Study dates
- 6 Nov 2025to 31 Aug 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 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.
Who cannot join
- 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,
Show all 24Show fewer
- 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,
- Hemoglobin ≥ 17 g/dL at enrollment,
- ALT or AST > 2.5 times upper limit of normal at enrollment,
- Total bilirubin > 2.5 times upper limit of normal at enrollment,
- Uric acid ≥ 7 mg/dL at enrollment.
- History of gastrointestinal tract perforation,
- History of diverticulitis (diverticulosis is not an exclusion),
- Plan for surgical procedure (other than bronchoscopy) within 120 days of enrollment.
- Inability or unwillingness to give written informed consent or comply with the study protocol,
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
University of Utah
Saint Lake City, Utah, 84112
Ramsey R Hachem, MD, 8015817806, ramsey.hachem@hsc.utah.edu
Julia Uddenberg, 8016466126, julia.uddenberg@hsc.utah.edu
- Recruiting
Washington University School, of Medicine, Barnes-Jewish Hospital
St Louis, Missouri, 63110
Derek E Byers, MD, PhD, 3144548766, dbyers@wustl.edu
Brigitte Mittler, CCRC, 3147471931, b.mittler@wustl.edu
About this study
Official title: A Phase 1 Clinical Trial of Siltuximab for the Treatment of Antibody-Mediated Rejection After Lung Transplantation (Siltux-AMR)
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
Read the detailed description
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.
- Being tested
- Siltuximab, Placebo
- Keywords
- lung transplant, antibody mediated rejection, transplant rejection, IL-6 blockade, donor specific antibodies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SiltuximabDrug
Interleukin-6 blockade
PlaceboDrug
Siltuximab placebo IV
| Study group | Role | What they receive |
|---|---|---|
| Siltuximab full-dose (11mg/kg) IV | Experimental | Siltuximab 11mg/kg IV on Days 1 and 22 Receives: Drug: Siltuximab |
| Siltuximab half-dose (5.5mg/kg) IV | Experimental | Siltuximab 5.5 mg/kg IV on Days 1 and 22 Receives: Drug: Siltuximab |
| Placebo IV | Placebo comparator | Placebo IV on Days 1 and 22 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From Randomization to Day 90.
Secondary outcomes (11)
incidence of CTCAE ≥ grade 3
Measured: during a period of 180 days after randomization
serum high-sensitivity CRP
Pharmacodynamic measure of Il-6 pathway blockade.
Measured: Up to 90 and 180 days after randomization
Blood Sultiximab levels
pharmacokinetic measure
Measured: Up to 90 days after randomization
Clearance of donor specific antibodies
Measured: From randomization to day 180
Infections
Confirmed bacterial, CMV (defined as a positive blood viral load ≥ 200 IU/mL), mold, mycobacterial, community-acquired respiratory viral infection (each assessed independently), or other opportunistic infection
Measured: Between randomization and day 180
Change in Forced Vital Capacity (FVC)
Measured: between randomization and day 180
Change in Forced Expiratory Volume in One Second (FEV1)
Measured: between randomization and day 180
Development of Chronic Lung Allograft Dysfunction
Development of probable CLAD according to the 2019 ISHLT criteria
Measured: between randomization and day 180
Allograft survival
Allograft survival defined as death or undergoing re-transplantation
Measured: between randomization and day 180
Hyperuricemia
Blood uric acid > 7 mg/dL
Measured: between randomization and day 180
Hyperlipidemia
Hyperlipidemia requiring the initiation or dose increase of medical therapy
Measured: between randomization and day 180
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2025
- Study start6 Nov 2025
- Primary completion30 Dec 2027 (estimated)
- Study completion31 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Antibody Mediated Rejection of Lung TransplantStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized 1:1:1
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Derek E Byers, MD, PhD, Washington University School of Medicine
- Investigators
- Ramsey Hachem, MD, Principal investigator, University of UtahDerek Byers, MD, PhD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06990711
- Sponsor's protocol ID
- SILTUX_AMR2025
- Other IDs
- 7R61HL169189-02
- Acronym
- Siltux-AMR
- Status last verified
- Aug 2026
- First submitted
- 18 May 2025
- Last updated
- 27 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: final determination pending
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Clinical Trial of Siltuximab for the Treatment of Antibody-Mediated Rejection After Lung Transplantation (Siltux-AMR)
- ClinicalTrials.gov ID
- NCT06990711
- Acronym / sponsor ID
- Siltux-AMR / SILTUX_AMR2025
- Keywords
- lung transplant, antibody mediated rejection, transplant rejection, IL-6 blockade, donor specific antibodies
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), University of Utah
- Study start
- 6 Nov 2025 (actual)
- Primary completion
- 30 Dec 2027 (estimated)
- Study completion
- 31 Aug 2028 (estimated)
- First posted
- 25 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
- Model description
- Randomized 1:1:1
| Arm | Type | Receives |
|---|---|---|
| Siltuximab full-dose (11mg/kg) IV | Experimental | Drug: SiltuximabSiltuximab 11mg/kg IV on Days 1 and 22 |
| Siltuximab half-dose (5.5mg/kg) IV | Experimental | Drug: SiltuximabSiltuximab 5.5 mg/kg IV on Days 1 and 22 |
| Placebo IV | Placebo comparator | Drug: PlaceboPlacebo IV on Days 1 and 22 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 18 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,
Key exclusion criteria (24 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SiltuximabInterleukin-6 blockade | Drug | Siltuximab full-dose (11mg/kg) IV, Siltuximab half-dose (5.5mg/kg) IV |
| PlaceboSiltuximab placebo IV | Drug | Placebo IV |
Primary outcome
Incidence of CTCAE ≥ grade 3
Time frame: From Randomization to Day 90.
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.
11 secondary outcomes
incidence of CTCAE ≥ grade 3
Time frame: during a period of 180 days after randomization
serum high-sensitivity CRP
Time frame: Up to 90 and 180 days after randomization
Blood Sultiximab levels
Time frame: Up to 90 days after randomization
Clearance of donor specific antibodies
Time frame: From randomization to day 180
Infections
Time frame: Between randomization and day 180
Change in Forced Vital Capacity (FVC)
Time frame: between randomization and day 180
Change in Forced Expiratory Volume in One Second (FEV1)
Time frame: between randomization and day 180
Development of Chronic Lung Allograft Dysfunction
Time frame: between randomization and day 180
Allograft survival
Time frame: between randomization and day 180
Hyperuricemia
Time frame: between randomization and day 180
Hyperlipidemia
Time frame: between randomization and day 180
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2026.
- Individual participant dataSharing planned: Undecided. final determination pending
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Washington University School, of Medicine, Barnes-Jewish Hospital
St Louis, United States
Ramsey Hachem, MD principal investigator
University of Utah
Derek Byers, MD, PhD principal investigator
Washington University School of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Siltuximab in people with Antibody Mediated Rejection of Lung Transplant, run by Washington University School of Medicine at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of CTCAE ≥ grade 3 (time frame: From Randomization to Day 90.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2026.