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Clinical Trial for Kidney Transplant Recipients

IMAGINE (Interleukin 6 blockade Modifying Antibody mediated Graft INjury and eGFR decline) is a pivotal Phase 3 trial to evaluate the safety and efficacy of clazakizumab for the treatment of chronic active antibody-mediated rejection (CABMR) in kidney transplant recipients.

Who can participate?

Participants in the IMAGINE Trial must be:

  • 18-70 years old
  • Kidney transplant recipients ≥ 6 months from time of transplant
  • Diagnosed with CABMR

What is Antibody Mediated Rejection?

Active antibody-mediated rejection (ABMR), especially chronic active antibody mediated rejection (CABMR), is now recognized as the most common cause of allograft failure after a successful kidney transplant. Current standard of care anti-rejection treatments target cellular-mediated (i.e., T cell-mediated rejection (TCMR)) processes and do not affect this antibody-mediated process. Currently, there are no approved treatments for active ABMR, including CABMR.

What is Clazakizumab?

Clazakizumab is a monoclonal antibody that binds to the cytokine interleukin 6 (IL-6), thereby inhibiting IL-6 signaling and activity.  IL-6 appears to be a critical cytokine involved in ABMR. It promotes the development and maturation of B cells to plasma cells that produce donor-specific antibodies (DSA) targeting the allograft. These DSAs damage the allograft and induce graft endothelial cells to produce inflammatory and pro-thrombotic molecules. Furthermore, IL-6 shapes the T cell immune response resulting in promotion of long-lived pro-inflammatory T helper cells and inhibition of immune regulatory T cells. 

What is the IMAGINE Trial?

The IMAGINE Trial investigates whether clazakizumab may be beneficial for the treatment of CABMR in recipients of a kidney transplant by inhibiting the production of DSA and re-shaping T cell alloimmune responses.

Who is Overseeing the IMAGINE Trial?

The IMAGINE Trial is being guided by a Steering Committee comprised of leading experts in the field of kidney transplantation. More information about the IMAGINE Steering Committee can be found here.

FOR MORE INFORMATION:

Please visit the IMAGINE TRIAL on ClinicalTrials.gov for complete information, including eligibility criteria. ClinicalTrials.gov Identifier: NCT03744910

Further information for clinicians:

Indication

Treatment of CABMR in kidney transplant recipients

Study Design

Randomized, double-blind, placebo-controlled, Phase 3 multi-center study, conducted globally.

Primary Objectives

  1. To evaluate the efficacy of clazakizumab in preventing all-cause composite allograft loss due to CABMR (defined as return to dialysis, allograft nephrectomy, re-transplantation, estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2 or death from any cause).
  2. To evaluate the efficacy of clazakizumab in slowing/preventing the progressive loss of kidney function (as measured by eGFR).
  3. To evaluate the safety of clazakizumab.

Secondary Objectives

  1. To evaluate the effects of clazakizumab on death-censored allograft loss (defined as return to dialysis, allograft nephrectomy, re-transplantation or eGFR <15 mL/min/1.73 m2 but excluding death from any cause).
  2. To evaluate the effects of clazakizumab on albuminuria.
  3. To evaluate the effects of clazakizumab on DSA titers and mean fluorescence intensity scores.
  4. To evaluate the effects of clazakizumab on incidence of acute rejection episodes (TCMR and ABMR).
  5. To evaluate the effects of clazakizumab on the histology of kidney biopsies according to the Banff 2015 lesion grading scores.
  6. To evaluate the effects of clazakizumab on overall patient survival.
  7. To evaluate the effects of clazakizumab on healthcare utilization due to ABMR and patient reported outcomes including health-related quality of life.

Number of Subjects

It is estimated that 350 subjects will be randomized to clazakizumab or placebo.

For general information about this study please contact Vitaeris at 844-448-2580.

Our Expanded Access Policy

Vitaeris is now part of CSL Behring! We are pleased to become part of CSL Behring, a well-established, global industry leader, and know that the future of clazakizumab is in excellent hands. Together, we have already achieved much progress through our partnership over the past few years and are now in an even stronger position to realize our collective goal of addressing one of the greatest unmet needs in the organ transplant community.

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