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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03744910




Registration number
NCT03744910
Ethics application status
Date submitted
6/11/2018
Date registered
19/11/2018
Date last updated
24/04/2024

Titles & IDs
Public title
Clazakizumab for the Treatment of Chronic Active Antibody Mediated Rejection in Kidney Transplant Recipients
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
Secondary ID [1] 0 0
2018-003682-34
Secondary ID [2] 0 0
CSL300_3001
Universal Trial Number (UTN)
Trial acronym
IMAGINE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Antibody-mediated Rejection 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Clazakizumab
Treatment: Drugs - Physiologic saline solution

Active comparator: Clazakizumab - Clazakizumab is a genetically engineered humanized immunoglobulin G1 (IgG1) mAb that binds to human IL-6 that is administered subcutaneously.

Placebo comparator: Placebo - Physiologic saline solution that is administered subcutaneously.


Treatment: Other: Clazakizumab
Clazakizumab is a genetically engineered humanized immunoglobulin G1 (IgG1) mAb that binds to human IL-6

Treatment: Drugs: Physiologic saline solution
Normal saline
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to composite all-cause allograft loss or irreversible loss of allograft function
Timepoint [1] 0 0
Up to approximately 8 years
Secondary outcome [1] 0 0
Time to composite all-cause allograft loss
Timepoint [1] 0 0
Baseline and up to approximately 8 years
Secondary outcome [2] 0 0
Incidence and time to irreversible loss of allograft function
Timepoint [2] 0 0
Baseline and up to approximately 8 years
Secondary outcome [3] 0 0
Incidence of composite all-cause allograft loss or irreversible loss of allograft function
Timepoint [3] 0 0
Up to approximately 8 years
Secondary outcome [4] 0 0
Incidence and time to death-censored allograft loss
Timepoint [4] 0 0
Up to approximately 8 years
Secondary outcome [5] 0 0
Change in mean estimated glomerular filtration rate (eGFR) from Baseline to End of Treatment (EOT)
Timepoint [5] 0 0
Baseline and up to approximately 8 years
Secondary outcome [6] 0 0
Change in spot urine albumin creatinine ratio (UACR) from Baseline to EOT
Timepoint [6] 0 0
Baseline and up to approximately 8 years
Secondary outcome [7] 0 0
Change in (Donor-specific antibodies) DSA titers and Mean fluorescence intensity (MFI) scores from Baseline to EOT
Timepoint [7] 0 0
Baseline and up to approximately 8 years
Secondary outcome [8] 0 0
Change in Banff lesion grading score (2015 criteria [Loupy et al, 2017]) of pre-treatment to post-treatment (Week 52) kidney biopsies
Timepoint [8] 0 0
Up to 52 weeks
Secondary outcome [9] 0 0
Incidence of acute rejection episodes of T cell-mediated rejection(TCMR) and Antibody-mediated rejection (ABMR) from Baseline to EOT
Timepoint [9] 0 0
Baseline and up to 8 years
Secondary outcome [10] 0 0
Overall patient survival
Timepoint [10] 0 0
Up to approximately 8 years
Secondary outcome [11] 0 0
Maximum concentration (Cmax, Cmax ss) of CSL300
Timepoint [11] 0 0
Up to 21 days
Secondary outcome [12] 0 0
Trough concentrations (Ctrough, Ctrough ss) of CSL300
Timepoint [12] 0 0
Up to 21 days
Secondary outcome [13] 0 0
Area under the concentration-time curve (AUC0-tau) at steady state of CSL300
Timepoint [13] 0 0
Up to 21 days
Secondary outcome [14] 0 0
Time of maximum concentration (Tmax, Tmax ss) of CSL300
Timepoint [14] 0 0
Up to 21 days

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/10/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/04/2024
Sample size
Target
Accrual to date
Final
194
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
WSLHD, Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [4] 0 0
The University of Queensland - Princess Alexandra Hospital (PAH) - Woolloongabba
Recruitment hospital [5] 0 0
Monash Health Monash Medical Centre - Clayton
Recruitment hospital [6] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment hospital [7] 0 0
Sir Charles Gairdner Hospital (SCGH) - Nedlands
Recruitment hospital [8] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [9] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [10] 0 0
Linear Clinical Research - Nedlands
Recruitment hospital [11] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment postcode(s) [5] 0 0
3064 - Parkville
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment postcode(s) [7] 0 0
- Adelaide
Recruitment postcode(s) [8] 0 0
- Camperdown
Recruitment postcode(s) [9] 0 0
- Clayton
Recruitment postcode(s) [10] 0 0
- Nedlands
Recruitment postcode(s) [11] 0 0
- Westmead
Recruitment postcode(s) [12] 0 0
- Woolloongabba
Recruitment outside Australia
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Yangsan
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Hualien City
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New Taipei City
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Taichang
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Taipei
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Taiwan
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Taoyuan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
CSL Behring
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
ICON Clinical Research
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT03744910
Trial related presentations / publications
Jordan SC, Ammerman N, Choi J, Huang E, Najjar R, Peng A, Sethi S, Sandhu R, Atienza J, Toyoda M, Ge S, Lim K, Gillespie M, Zhang X, Haas M, Vo A. Evaluation of Clazakizumab (Anti-Interleukin-6) in Patients With Treatment-Resistant Chronic Active Antibody-Mediated Rejection of Kidney Allografts. Kidney Int Rep. 2022 Feb 9;7(4):720-731. doi: 10.1016/j.ekir.2022.01.1074. eCollection 2022 Apr.
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
CSL Behring
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03744910