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
Primary Objectives: 1. To evaluate the efficacy of clazakizumab in preventing all-cause composite allograft loss due to CABMR (defined as return to dialysis, allograft nephrectomy, re-transplantation, eGFR <15 mL/min/1.73 m2 or death from any cause (including death with functioning allograft). 2. To evaluate the efficacy of clazakizumab in slowing/preventing the progressive loss of kidney function (as measured by eGFR using the MDRD4 equation). 3. To evaluate the safety of clazakizumab. Secondary Objectives: 1. To evaluate the effects of clazakizumab on death-censored allograft loss (defined as return to dialysis, allograft nephrectomy, re-transplantation or eGFR <15 mL/min/1.73 m2 but excluding death from any cause). 2. To evaluate the effects of clazakizumab on albuminuria. 3. To evaluate the effects of clazakizumab on DSA titers and mean fluorescence intensity (MFI) scores. 4. To evaluate the effects of clazakizumab on incidence of acute rejection episodes (TCMR and ABMR). 5. To evaluate the effects of clazakizumab on the histology of kidney biopsies according to the Banff 2015 lesion grading scores. 6. To evaluate the effects of clazakizumab on overall patient survival. 7. To evaluate the effects of clazakizumab on healthcare utilization due to ABMR and patient reported outcomes, including health-related quality of life (HRQoL).
This multi-center, randomized, double-blind, parallel-group, placebo-controlled, Phase 3 trial investigates whether clazakizumab (an anti-IL-6 mAb) may be beneficial for the treatment of CABMR in kidney transplant recipients by inhibiting the production of DSA and re-shaping T cell alloimmune responses. Subjects will be administered clazakizumab at a target dose of 12.5 mg (or placebo) by SC injection, Q4W for up to 260 weeks (or until allograft loss or death).
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Inclusion Criteria: 1. Age 18-70 years. 2. Living donor/deceased donor kidney transplant recipients ≥6 months from time of transplant. 3. Diagnosis of CABMR (according to Banff 2015 diagnostic criteria) to include all of the following: a. Biopsy-proven CABMR (i.e., chronic glomerulopathy (cg) >0) with/without C4d staining. Repeat biopsy to be performed if previous biopsy is not within 6 months of the start of the screening period. The local pathologist’s diagnosis will be reviewed by a central pathologist to confirm eligibility for entry into the study. Subjects without evidence of chronic tissue injury on light microscopy but who have glomerular basement membrane double contours on electron microscopy (cg1a) are eligible. b. Positive for HLA DSA (using single-antigen bead-based assays) post-transplant. Local laboratory DSA results will be reviewed by the central HLA reviewer to confirm eligibility for entry into the study. A single antigen bead MFI >1,000 will be considered positive. If presence of HLA DSA is confirmed within 6 months of the start of the screening period, the test does not need to be repeated for eligibility. c. Note: Treatments for ABMR (including CABMR) or TCMR are not allowed within 3 months of the start of screening (see Exclusion Criterion 3). If subject has received one of these treatments at any time prior, a repeat biopsy and repeat DSA must be performed after halting/completing treatment (to show continuing CABMR). 4. Written informed consent obtained from subject (or legally acceptable representative) before any trial-related procedures. Detailed exclusion criteria also apply.
Treatment
National
Outpatient CTRC
Pathology - SOM
University of Colorado Hospital
James Cooper, MD
Protocol Number: 19-0460
More information available at ClinicalTrials.gov: NCT03744910
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