What is the mechanism of action of this treatment?

The most common treatments for Antibody Mediated Rejection (AMR) include monoclonal antibodies like clazakizumab, which targets IL-6, a cytokine involved in B cell activation and antibody production. By inhibiting IL-6, clazakizumab reduces inflammation and antibody-mediated damage to the graft. Other treatments include plasmapheresis to remove antibodies, IVIG to neutralize them, and rituximab to deplete B cells. These therapies are crucial for AMR patients as they help control the immune response, preventing graft rejection and improving transplant success.

What side effects are associated with this type of intervention?

Common treatments for Antibody Mediated Rejection (AMR) include monoclonal antibodies like rituximab and immunosuppressive therapies such as cyclophosphamide and plasmapheresis. Rituximab can cause infusion reactions, serum-sickness-like reactions, and in rare cases, progressive multifocal leukoencephalopathy. Cyclophosphamide is associated with bone marrow suppression, increased risk of infections, and potential bladder toxicity. Plasmapheresis can lead to complications such as hypotension, bleeding, and allergic reactions. Clazakizumab, being an anti-IL-6 monoclonal antibody, may have side effects similar to other monoclonal antibodies, including infusion-related reactions and increased risk of infections.

What prior FDA approvals exist?

The FDA has approved several monoclonal antibodies and immunosuppressive agents for conditions related to Antibody Mediated Rejection (AMR). Rituximab, an anti-CD20 monoclonal antibody, has been used off-label for AMR due to its ability to deplete B cells. Additionally, intravenous immunoglobulin (IVIG) and plasmapheresis are commonly used to manage AMR by reducing circulating antibodies. While Clazakizumab, an anti-IL-6 monoclonal antibody, is currently being studied for its efficacy in treating chronic active AMR, similar agents like Tocilizumab (another anti-IL-6 receptor antibody) have shown promise in managing transplant rejection and other autoimmune conditions.

What other types of research exist?

Promising alternatives to Clazakizumab for Antibody Mediated Rejection in 2024 include anti-IL-23 agents such as ustekinumab and mirikizumab, which have demonstrated efficacy and a favorable safety profile in other inflammatory conditions. Additionally, belatacept, a costimulation blocker, has shown potential in kidney transplantation and may be considered for AMR management.

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Monoclonal Antibodies

Clazakizumab for Antibody Mediated Rejection (IMAGINE Trial)

Phase 3

Waitlist Available

Research Sponsored by CSL Behring

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

To be considered for determination of study eligibility, the biopsy and DSA analysis must be performed at least 2 months ± 2 weeks after the end of any prior treatment for acute antibody-mediated rejection (ABMR) or T-cell-mediated rejection (TCMR), in order to show continuing CABMR and presence of HLA DSA

Serologic evidence of circulating DSA to HLA. The local laboratory DSA results must be reviewed and confirmed by the central HLA reviewer during the screening period

Must not have

History of human immunodeficiency virus (HIV) infection or positive for HIV

Treatment for ABMR (including CABMR) or TCMR within 3 months prior to the start of screening with the exception of steroids

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 8 years

Awards & highlights

Pivotal Trial

Summary

This trial tests clazakizumab, a drug that blocks IL-6, in kidney transplant patients with chronic rejection. The goal is to see if it can reduce the immune system's attack on the transplanted kidney and improve its function. Clazakizumab is being tested for its potential to counteract rejection in kidney transplant patients.

Who is the study for?

This trial is for kidney transplant recipients aged 18-75 who are at least 6 months post-transplant and have chronic active antibody-mediated rejection (CABMR). Participants must show specific biopsy signs of CABMR, confirmed by a central pathologist, and have circulating donor-specific antibodies. Pregnant individuals or those with recent treatments for rejection, certain infections like TB or hepatitis, HIV, or multiple organ transplants other than kidney-pancreas are excluded.

What is being tested?

The trial tests clazakizumab's effectiveness and safety against CABMR in kidney transplant patients. Clazakizumab is an anti-interleukin-6 monoclonal antibody designed to reduce inflammation caused by the body's immune response to the transplanted kidney.

What are the potential side effects?

Potential side effects of clazakizumab may include reactions where the drug is injected, increased risk of infections due to immune system suppression, liver issues, changes in blood cell counts leading to fatigue or bruising easily, and possible interference with cholesterol levels.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My last treatment for rejection was at least 2 months ago, and I still have CABMR with HLA DSA present.

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My blood test shows antibodies against a transplant.

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My kidney rejection is ongoing and confirmed by biopsy and specific blood tests.

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I am between 18 and 75 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am HIV positive or have a history of HIV.

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I have not been treated for ABMR or TCMR, except with steroids, in the last 3 months.

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I have active TB or had it in the past.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 8 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 8 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 8 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Time to composite all-cause allograft loss or irreversible loss of allograft function

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Active Control

Placebo Group

Group I: ClazakizumabActive Control1 Intervention

Clazakizumab is a genetically engineered humanized immunoglobulin G1 (IgG1) mAb that binds to human IL-6 that is administered subcutaneously.

Group II: PlaceboPlacebo Group1 Intervention

Physiologic saline solution that is administered subcutaneously.

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Antibody Mediated Rejection (AMR) include monoclonal antibodies like clazakizumab, which targets IL-6, a cytokine involved in B cell activation and antibody production. By inhibiting IL-6, clazakizumab reduces inflammation and antibody-mediated damage to the graft. Other treatments include plasmapheresis to remove antibodies, IVIG to neutralize them, and rituximab to deplete B cells. These therapies are crucial for AMR patients as they help control the immune response, preventing graft rejection and improving transplant success.