Studie zur Bewertung der Wirksamkeit und Sicherheit der Behandlung des Prüfmedikaments Clazakizumab im Vergleich zu einem Placebo (inaktive Substanz) bei Empfängern von Nierentransplantationen mit chronisch aktiver Antikörper-vermittelter Abstoßung (CABMR)

Biological: Clazakizumab;Drug: Physiologic saline solution

- Inclusion criteria:

1. Age 18-75 years.

2. Living donor/deceased donor kidney transplant recipients =6 months from time of
transplant.

3. Diagnosis of CABMR determined by kidney biopsy and the presence of HLA DSA using
single-antigen bead-based assays.

NOTE: If conducted within 12 months (+3 weeks) prior to the start of the
screening period, and no intervening treatments have been administered, the
biopsy does not need to be repeated at Screening. If conducted within 6 months (+
3 weeks) prior to the start of Screening, the DSA analysis does not need to be
repeated at screening. 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 ABMR (including CABMR) or TCMR, in order to
show continuing CABMR and presence of HLA DSA. In addition, with the exception of
steroids, treatments for ABMR or TCMR are not allowed within 3 months prior to
the start of screening.

The following histopathologic and serologic diagnostic criteria (based on Banff
2015 criteria [Loupy et al, 2017]) 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,
including 1 or more of the following.

- Linear C4d staining in peritubular capillaries or medullary vasa recta (C4d2
or C4d3 by immunofluorescence on frozen sections, or C4d > 0 by
immunohistochemistry on paraffin sections).

- At least moderate microvascular inflammation ([g + ptc] = 2) in the absence
of recurrent or de novo glomerulonephritis, although in the presence of
acute TCMR, borderline infiltrate, or infection, ptc = 2 alone is not
sufficient and g must be = 1.

NOTE: The local pathologist's diagnosis must be reviewed by a central pathologist
to confirm eligibility for entry into the study. Biopsies with other
histopathologic changes (eg, BKV nephropathy or recurrent glomerulonephritis) may
be eligible if concurrent CABMR changes (as detailed above) are present and
determined to be the predominant cause of renal dysfunction.

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

- Exclusion criteria:

1. Multi-organ transplant recipient (except for simultaneous kidney-pancreas or
previous multiple kidney transplants) or cell transplant (islet, bone marrow,
stem cell) recipient.

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

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

4. Pregnant, breastfeeding, or unwillingness to practice adequate contraception.

5. Active tuberculosis (TB) or history of active TB.

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

7. Seropositive for hepatitis B surface antigen (HBsAg)

8. Hepatitis C virus (HCV) RNA positive.