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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03744910
Recruitment Status : Recruiting
First Posted : November 19, 2018
Last Update Posted : April 25, 2023
Sponsor:
Collaborator:
ICON Clinical Research
Information provided by (Responsible Party):
CSL Behring

Study Description
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Brief Summary:
This trial investigates the efficacy and safety of clazakizumab [an anti-interleukin (IL)-6 monoclonal antibody (mAb)] for the treatment of CABMR in recipients of a kidney transplant.

Condition or disease Intervention/treatment Phase
Antibody-mediated Rejection Biological: Clazakizumab Drug: Physiologic saline solution Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 350 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : October 14, 2019
Estimated Primary Completion Date : February 2030
Estimated Study Completion Date : February 2030

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Clazakizumab
Clazakizumab is a genetically engineered humanized immunoglobulin G1 (IgG1) mAb that binds to human IL-6 that is administered subcutaneously.
 Biological: Clazakizumab
Clazakizumab is a genetically engineered humanized immunoglobulin G1 (IgG1) mAb that binds to human IL-6
Placebo Comparator: Placebo
Physiologic saline solution that is administered subcutaneously.
 Drug: Physiologic saline solution
Normal saline


Outcome Measures
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Primary Outcome Measures :
  1. Time to all-cause composite allograft loss [ Time Frame: Up to 5.5 years ]

    Defined as:

    • eGFR < 15 mL/min/1.73 m2*,
    • eGFR < 15 mL/min/1.73 m2*,
    • return to dialysis*,
    • allograft nephrectomy,
    • retransplantation, or
    • death from any cause (Final Analysis), *total cumulative duration of eGFR < 15 mL/min/1.73 m2 AND / OR dialysis ≥ 60 days.

    An eGFR < 15 mL/min/1.73 m2 must be confirmed by a repeat measurement. The time window for confirmation of an eGFR < 15 mL/min/1.73 m2 is ≥ 60 days from when initially noted. The date of the initial eGFR < 15 mL/min/1.73 m2 is the date when first determined from local or central laboratories. The primary efficacy endpoint will be analyzed as part of the final analysis when at least 221 all-cause composite allograft loss events have occurred



Secondary Outcome Measures :
  1. Incidence and time to loss of allograft function as defined by a 40% decline in eGFR from Baseline [ Time Frame: Baseline and Up to approximately 7 years ]
  2. Incidence and time to all-cause composite allograft loss [ Time Frame: Up to approximately 7 years ]
  3. Incidence and time to death-censored allograft loss [ Time Frame: Up to approximately 7 years ]
  4. Change in mean estimated glomerular filtration rate (eGFR) from Baseline to End of Treatment (EOT) [ Time Frame: Baseline and Up to approximately 7 years ]
  5. Change in spot urine albumin creatinine ratio (UACR) from Baseline to EOT [ Time Frame: Baseline and Up to approximately 7 years ]
  6. Change in (Donor-specific antibodies) DSA titers and Mean fluorescence intensity (MFI) scores from Baseline to EOT [ Time Frame: Baseline and Up to approximately 7 years ]
  7. 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 approximately 7 years ]
  8. Change in Banff lesion grading score (2015 criteria [Loupy et al, 2017]) of pretreatment to posttreatment (Week 52) kidney biopsies [ Time Frame: Up to 52 weeks ]
  9. Overall patient survival [ Time Frame: Up to approximately 7 years ]
  10. Maximum concentration (Cmax, Cmax ss) of CSL300 [ Time Frame: Up to 21 days ]
  11. Trough concentrations (Ctrough, Ctrough ss) of CSL300 [ Time Frame: Up to 21 days ]
  12. Area under the concentration-time curve (AUC0-tau) at steady state of CSL300 [ Time Frame: Up to 21 days ]
  13. Time of maximum concentration (Tmax, Tmax ss) of CSL300 [ Time Frame: Up to 21 days ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

      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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03744910


Contacts
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Contact: Trial Registration Coordinator 610-878-4000 clinicaltrials@cslbehring.com

Locations
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Sponsors and Collaborators
CSL Behring
ICON Clinical Research
Investigators
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Study Director: Study Director CSL Behring
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT03744910    
Other Study ID Numbers: CSL300_3001
2018-003682-34 ( EudraCT Number )
VKTX01 ( Other Identifier: Vitaeris )
First Posted: November 19, 2018    Key Record Dates
Last Update Posted: April 25, 2023
Last Verified: April 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by CSL Behring:
Chronic Active
Antibody-mediated Rejection (AMR)