Clazakizumab for the Treatment of Chronic Active Antibody Mediated Rejection in Kidney Transplant Recipients

• Register: ClinicalTrials.gov
• Last refreshed on: 6 May 2024
• Main ID: NCT03744910
• Date of registration: 06/11/2018
• Prospective Registration: Yes
• Primary sponsor: CSL Behring
• Public title: Clazakizumab for the Treatment of Chronic Active Antibody Mediated Rejection in Kidney Transplant Recipients IMAGINE
• Scientific title: A Pivotal Phase 3 Trial to Evaluate the Safety and Efficacy of Clazakizumab for the Treatment of Chronic Active Antibody-mediated Rejection in Kidney Transplant Recipients
• Date of first enrolment: October 14, 2019
• Target sample size: 194
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/ct2/show/NCT03744910
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Australia, Austria, Belgium, Canada, Czechia, France, Germany, Hungary, Korea, Republic of, Netherlands, New Zealand, Spain, Sweden, Taiwan, United States

Contacts

• Name: Study Director
• Affiliation: CSL Behring

Key inclusion & exclusion criteria

- 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. For eligibility, kidney biopsy must not be
older than 12 months and DSA analysis must be performed no longer than 6 months
prior to the start of Screening.

NOTE: • Within 3 months prior to the start of Screening, treatments for ABMR or
TCMR, with the exception of steroids*, are not allowed (see Exclusion Criterion
3).

• If treatment for ABMR (including CABMR) or TCMR (other than steroids*) was
given between 3 to 12 months of Screening, a repeat kidney biopsy and DSA
analysis are required at least 6 weeks after the end of treatment to confirm
continuing CABMR and presence of HLA DSA and to determine eligibility.

* A maximum dose of 2g of methylprednisolone intravenously (or dose equivalent of
other steroids), followed by a taper to the original maintenance steroid dose is
allowed.

The following histopathologic and serologic diagnostic criteria (based on Banff
2015 criteria [Loupy et al, 2017]) must be met for inclusion:

1. Morphologic evidence of chronic tissue injury, as demonstrated by transplant
glomerulopathy (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.

2. Evidence of current/recent antibody interaction with vascular endothelium,
including 1 or more of the following:

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

ii. At least moderate microvascular inflammation ([glomerulitis score, g +
peritubular capillaritis score, 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.

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

4. Written informed consent obtained from subject (or legally acceptable
representative) before any trial-related procedures.

- 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.



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Antibody-mediated Rejection

Intervention(s)

Biological: Clazakizumab

Drug: Physiologic saline solution

Primary Outcome(s)

Time to composite all-cause allograft loss or irreversible loss of allograft function [Time Frame: Up to approximately 8 years]

Secondary Outcome(s)

Incidence and time to death-censored allograft loss [Time Frame: Up to approximately 8 years]

Time of maximum concentration (Tmax, Tmax ss) of CSL300 [Time Frame: Up to 21 days]

Area under the concentration-time curve (AUC0-tau) at steady state of CSL300 [Time Frame: Up to 21 days]

Change in mean estimated glomerular filtration rate (eGFR) from Baseline to End of Treatment (EOT) [Time Frame: Baseline and up to approximately 8 years]

Incidence of composite all-cause allograft loss or irreversible loss of allograft function [Time Frame: Up to approximately 8 years]

Change in (Donor-specific antibodies) DSA titers and Mean fluorescence intensity (MFI) scores from Baseline to EOT [Time Frame: Baseline and up to approximately 8 years]

Change in Banff lesion grading score (2015 criteria [Loupy et al, 2017]) of pre-treatment to post-treatment (Week 52) kidney biopsies [Time Frame: Up to 52 weeks]

Change in spot urine albumin creatinine ratio (UACR) from Baseline to EOT [Time Frame: Baseline and up to approximately 8 years]

Overall patient survival [Time Frame: Up to approximately 8 years]

Trough concentrations (Ctrough, Ctrough ss) of CSL300 [Time Frame: Up to 21 days]

Incidence and time to irreversible loss of allograft function [Time Frame: Baseline and up to approximately 8 years]

Incidence of acute rejection episodes of T cell-mediated rejection(TCMR) and Antibody-mediated rejection (ABMR) from Baseline to EOT [Time Frame: Baseline and up to 8 years]

Maximum concentration (Cmax, Cmax ss) of CSL300 [Time Frame: Up to 21 days]

Time to composite all-cause allograft loss [Time Frame: Baseline and up to approximately 8 years]

Secondary ID(s)

2018-003682-34

CSL300_3001

VKTX01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

ICON Clinical Research