Siltuximab for Rejection

(Siltux-AMR Trial)

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must be taking: Carfilzomib, Anti-thymocyte globulin

Must not be taking: IL-6 blockers

Disqualifiers: Pregnancy, Lymphoma, Cancer, others

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and tolerability of a new drug, Siltuximab, for individuals experiencing antibody-mediated rejection after a lung transplant. Antibody-mediated rejection occurs when the immune system attacks the transplanted lung, potentially leading to lung failure. Participants will receive either a full dose, a half dose of Siltuximab, or a placebo (a harmless substance with no effect) to assess their response. Individuals who have recently undergone a lung transplant and are currently hospitalized for rejection treatment may be suitable candidates for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that siltuximab is being tested to determine its effectiveness in preventing rejection in lung transplant patients. Long-term safety information for siltuximab in transplants is not yet available, but some studies have provided insights into its safety. In past research with similar treatments for organ transplants, about 29% of patients experienced infections. These infections were not linked to any specific patient group or treatment factor, suggesting they might not be directly caused by the treatment.

This trial is in its early stages, focusing mainly on safety and patient tolerance. Researchers are closely monitoring patient responses and any side effects. Prospective participants should know that early-phase studies aim to identify serious side effects and ensure the treatment is safe for further research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Siltuximab is unique because it targets IL-6, a protein involved in inflammation, which is not typically addressed by standard rejection treatments like corticosteroids or calcineurin inhibitors. Unlike these conventional therapies, which broadly suppress the immune system, siltuximab specifically interferes with the inflammatory process by blocking IL-6, potentially reducing side effects associated with broader immune suppression. Researchers are excited about siltuximab because it offers a more targeted approach, which could improve effectiveness and safety in managing rejection.

What evidence suggests that Siltuximab might be an effective treatment for rejection?

Research suggests that siltuximab might help with antibody-mediated rejection (AMR) after lung transplants. Studies have shown that survival rates for lung transplant patients with AMR are low, with only about 50% living for one year and 20% for two years. Siltuximab blocks IL-6, a protein important in the body's immune response. By doing so, siltuximab may reduce harmful immune reactions and potentially improve survival rates. In this trial, participants will receive either a full dose, a half dose of siltuximab, or a placebo to evaluate its effectiveness in treating AMR. While current evidence focuses on its mechanism, more studies are needed to confirm its effectiveness in treating AMR. ^{1 6 7 8 9}

Who Is on the Research Team?

Ramsey Hachem, MD

Principal Investigator

University of Utah

Derek Byers, MD, PhD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for individuals who have undergone lung transplantation and are now experiencing antibody-mediated rejection. Participants should be stable enough to receive additional treatment on top of their routine immunosuppression.

Inclusion Criteria

I have high levels of specific antibodies against transplant markers.

I have a new diagnosis of antibody-mediated rejection and will be treated with Carfilzomib or anti-thymocyte globulin.

I understand the study's purpose and am willing to sign the consent form.

Exclusion Criteria

I have had diverticulitis before.

I am scheduled for surgery (not including bronchoscopy) within the next 4 months.

Pregnant or breast feeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Siltuximab or placebo intravenously on Days 1 and 22

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

26 weeks

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Siltuximab

Trial Overview

The study is testing the safety and tolerability of Siltuximab, a new immunosuppressive medication, when added to standard treatments for post-lung transplant rejection. It's an early-stage trial comparing Siltuximab with a placebo.

How Is the Trial Designed?

Group I: Siltuximab half-dose (5.5mg/kg) IV Experimental Treatment 1 Intervention

Siltuximab 5.5 mg/kg IV on Days 1 and 22

Group II: Siltuximab full-dose (11mg/kg) IV Experimental Treatment 1 Intervention

Siltuximab 11mg/kg IV on Days 1 and 22

Group III: Placebo IV Placebo Group 1 Intervention

Placebo IV on Days 1 and 22

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

University of Utah

Collaborator

Trials

1,169

Recruited

1,623,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06990711?aggFilters=status%3Anot

A Phase 1 Clinical Trial of Siltuximab for the Treatment ...

Long-term outcomes after lung transplantation remain disappointing, and the median survival is 6.7 years. Chronic lung allograft dysfunction (CLAD) is the ...

2.

trial.medpath.com

trial.medpath.com/clinical-trial/c14a04624b14a4e9/nct06990711-siltuximab-clinical-trial-lung-transplant-rejection

A Phase 1 Clinical Trial of Siltuximab for the Treatment of ...

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) ...

3.

reporter.nih.gov

reporter.nih.gov/project-details/11099734

Targeting the B Cell Response to Treat Antibody-Mediated Rejection

Establishing an effective and safe way to treat patients with established AMR would potentially increase the half-life of transplanted organs, extend the lives ...

4.

lidsen.com

lidsen.com/journals/transplantation/transplantation-09-03-258/obm.transplant.2503258.pdf

Antibody-Mediated Rejection in Kidney Transplantation

Abstract. Antibody-mediated rejection (ABMR) remains a major barrier to long-term graft survival in kidney transplantation.

5.

frontierspartnerships.org

frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2023.11751/full

The Incidence of Antibody-Mediated Rejection Is Age-Related ...

Ten years after transplantation the cumulative % of recipients with ABMR was 17% in young, 15% in middle age, and 12% in elderly recipients (p < ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12301192/

Comparative efficacy and safety of induction therapy in solid ...

Alemtuzumab emerged as the optimal therapy for minimizing rejection, while OKT3 and basiliximab were superior for graft and overall survival, ...

7.

journals.lww.com

journals.lww.com/transplantjournal/fulltext/2020/05000/recommended_treatment_for_antibody_mediated.11.aspx

Recommended Treatment for Antibody-mediated Rejection ...

There were no major differences in outcome, and Rituximab had a reasonable safety profile. However, small numbers, demographic, and baseline differences as ...

8.

academic.oup.com

academic.oup.com/ndt/article/40/8/1615/8152901

Antibody-mediated rejection—treatment standard

However, long-term safety data in transplantation are lacking, and the results of an ongoing phase 3 trial are awaited. Several novel ...

9.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0049017221001670

Safety of biologic treatments in solid organ transplant ...

Infections occurred in 54 patients (28.9%) through 88 recorded events. No therapeutic or demographic factors were associated with occurrence of infection.