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Table 1 Select inclusion and exclusion criteria

From: Clazakizumab for the treatment of chronic active antibody-mediated rejection (AMR) in kidney transplant recipients: Phase 3 IMAGINE study rationale and design

Inclusion criteria

1. Living donor/deceased donor kidney transplant recipients ≥6 months from time of transplant

2. Diagnosis of chronic active AMR determined by kidney biopsy and the presence of HLA DSA using single-antigen bead-based assays. The following histopathologic and serologic diagnostic criteria (based on Banff 2015 criteria [31] must be met for inclusion:

 • Morphologic evidence of chronic tissue injury, as demonstrated by TG (cg>0). Biopsies without evidence of chronic tissue injury on light microscopy, but with glomerular basement membrane double contours on electron microscopy (cg1a) are eligible

 • Evidence of current/recent antibody interaction with vascular endothelium

 • Serologic evidence of circulating HLA DSA

Key exclusion criteria

1. eGFR <25 mL/min/1.73 m2 or >65 mL/min/1.73 m2 (MDRD4)

2. Nephrotic range proteinuria defined as spot UACR ≥2200 mg/g (≥220 mg/mmol). If spot UACR is above defined limits, a single repeat test can be performed on a separate day to confirm ineligibility

3. Multiorgan transplant recipient (except for simultaneous kidney–pancreas or previous multiple kidney transplants) or cell transplant (islet, bone marrow, stem cell) recipient

4. Treatment for AMR (including chronic active AMR) or TCMR within 3 months of the start of screening

5. Received T-cell-depleting agents (e.g., alemtuzumab or anti-thymocyte globulin) within 3 months of the start of screening

6. Treatment with mTOR inhibitors within 4 weeks of the start of screening

7. Biopsy indicating predominant cause of renal dysfunction caused by pathology other than chronic active AMR

8. Impaired renal function due to disorders in the transplanted graft (e.g., renal artery stenosis or hydronephrosis)

9. Neutropenia (<1000/mm3) or thrombocytopenia (<50,000/mm3)

10. Prior exposure to clazakizumab, tocilizumab, or other IL-6/IL-6R blockers

11. ABO-incompatible transplant recipient

12. Severe hypogammaglobulinemia (defined as IgG <400 mg/dL)

13. Prior (within 2 years of the start of screening) exposure to proteasome inhibitors (e.g., bortezomib)

  1. The full list of criteria can be found at clinicaltrials.gov
  2. AMR antibody-mediated rejection, cg chronic glomerulopathy, DSA donor-specific antibodies, eGFR estimated glomerular fibrillation rate, HLA human leukocyte antigen, IgG immunoglobulin G, IL-6 interleukin-6, IL-6R IL-6 receptor, MDRD4 Modification of Diet in Renal Disease 4-variable version, mTOR mammalian target of rapamycin, TCMR T-cell-mediated rejection, TG transplant glomerulopathy, UACR urine albumin-to-creatinine ratio
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ISSN: 1745-6215