Antibody-mediated Rejection
Conditions
Keywords
Chronic Active, Antibody-mediated Rejection (AMR)
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.
Interventions
BIOLOGICALClazakizumab
Clazakizumab is a genetically engineered humanized immunoglobulin G1 (IgG1) mAb that binds to human IL-6
Normal saline
Sponsors
ICON Clinical Research
CSL Behring
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 52 in Estimated Glomerular Filtration Rate (eGFR) | From Baseline to Week 52 | This primary outcome measure was the one from the first interim analysis. |
| Number of Participants With Composite All-cause Allograft Loss or Irreversible Loss of Allograft Function | From Baseline to 4 years | Composite all-cause allograft loss or irreversible loss of allograft function, defined as time to first occurrence of any of the following components: * eGFR \< 15 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2)\* * return to dialysis\* * allograft nephrectomy * retransplantation * death from any cause, or * a sustained (greater than or equal to \[\>=\] 60 days) 40% decline in eGFR from Baseline. (\*Total cumulative duration of sustained eGFR \< 15 mL/min/1.73 m\^2 AND / OR dialysis \>= 60 days.) If the eGFR \< 15 mL/min/1.73 m\^2 was the only component reached, the value must be sustained over at least 60 days and must be confirmed by a repeat measurement after \>= 60 days from the first measurement. The number of participants with composite all-cause allograft loss or irreversible loss of allograft function are reported here. Time-to-event data were not calculated due to the study's termination. |
| Percentage of Participants With Composite All-cause Allograft Loss or Irreversible Loss of Allograft Function | From Baseline to 4 years | Composite all-cause allograft loss or irreversible loss of allograft function, defined as time to first occurrence of any of the following components: * eGFR \< 15 mL/min/1.73 m\^2\* * return to dialysis\* * allograft nephrectomy * retransplantation * death from any cause, or * a sustained (greater than or equal to \[\>=\] 60 days) 40% decline in eGFR from Baseline. (\*Total cumulative duration of sustained eGFR \< 15 mL/min/1.73 m\^2 AND / OR dialysis \>= 60 days.) If the eGFR \< 15 mL/min/1.73 m\^2 was the only component reached, the value must be sustained over at least 60 days and must be confirmed by a repeat measurement after \>= 60 days from the first measurement. The percentage of participants with composite all-cause allograft loss or irreversible loss of allograft function are reported here. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs) | Up to 4 years | — |
| Percentage of Participants With TEAEs, Serious TEAEs, and AESIs | Up to 4 years | — |
| Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) | From baseline up to 4 years | Number of participants who tested positive for BKV, CMV or EBV according to the maximum measured viral amount (International Units/mL \[IU/mL\]) after baseline are reported here. |
| Number of Participants With Abnormal Laboratory Test Results | Up to 4 years | Laboratory tests included liver function test (LFTs), complete blood count (CBC), plasma lipids, high-sensitivity C-reactive protein (hsCRP). Only participants with abnormal laboratory test results are reported here. Here, ULN = upper limit of normal, LLN = lower limit of normal, ALT = Alanine aminotransferase and AST = Aspartate aminotransferase. |
| Percentage of Participants With Abnormal Laboratory Test Results | Up to 4 years | Laboratory tests included LFTs, CBC, plasma lipids, hsCRP. Only percentage of participants with abnormal laboratory test results are reported here. Here, ULN = upper limit of normal, LLN = lower limit of normal, ALT = Alanine aminotransferase and AST = Aspartate aminotransferase. |
| Number of Participants With Clinically Significant Change in Vital Signs, Electrocardiograms (ECGs), and Physical Examination | Up to 4 years | — |
| Number of Participants With Positive Anti-drug Antibodies | Baseline, Weeks 12, 24, and 48 | — |
| Percentage of Participants With Positive Anti-drug Antibodies | Baseline, Weeks 12, 24, and 48 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration at Steady State (Cmax ss) of CSL300 | Up to Week 24 | A subset of participants (out of the enrolled participants in the main study) had the option to participate in a pharmacokinetic (PK)/ Pharmacodynamic (PD) sub-study. |
| Trough Concentrations at Steady State (Ctrough ss) of CSL300 | Up to Week 24 | A subset of participants (out of the enrolled participants in the main study) had the option to participate in a PK/PD sub-study. |
| Number of Participants With Composite All-cause Allograft Loss | From Baseline to 4 years | Composite all-cause allograft loss, defined as, time to first occurrence of any of the following components: * eGFR \< 15 mL/min/1.73 m\^2\* * return to dialysis\* * allograft nephrectomy * retransplantation, or * death from any cause. (\*Total cumulative duration of sustained eGFR \< 15 mL/min/1.73 m\^2 AND / OR dialysis \>= 60 days.) If the eGFR \< 15 mL/min/1.73 m\^2 was the only component reached, the value must be sustained over at least 60 days and must be confirmed by a repeat measurement after \>= 60 days from the first measurement. The number of participants with composite all-cause allograft loss are reported here. |
| Time of Maximum Concentration at Steady State (Tmax ss) of CSL300 | Up to Week 24 | A subset of participants (out of the enrolled participants in the main study) had the option to participate in a PK/PD sub-study. |
| Area Under the Concentration-time Curve (AUC0-tau) at Steady State of CSL300 | Up to Week 24 | A subset of participants (out of the enrolled participants in the main study) had the option to participate in a PK/PD sub-study. |
| Percentage of Participants With Composite All-cause Allograft Loss | From Baseline to 4 years | Composite all-cause allograft loss, defined as, time to first occurrence of any of the following components: * eGFR \< 15 mL/min/1.73 m\^2\* * return to dialysis\* * allograft nephrectomy * retransplantation, or * death from any cause. (\*Total cumulative duration of sustained eGFR \< 15 mL/min/1.73 m\^2 AND / OR dialysis \>= 60 days.) If the eGFR \< 15 mL/min/1.73 m\^2 was the only component reached, the value must be sustained over at least 60 days and must be confirmed by a repeat measurement after \>= 60 days from the first measurement. The percentage of participants with composite all-cause allograft loss are reported here. |
| Number of Participants With Irreversible Loss of Allograft Function | From Baseline to 4 years | Irreversible loss of allograft function as defined by a 40% decline in eGFR from Baseline sustained for at least 60 days. |
| Percentage of Participants With Irreversible Loss of Allograft Function | From Baseline to 4 years | Irreversible loss of allograft function as defined by a 40% decline in eGFR from Baseline sustained for at least 60 days. |
| Number of Participants With Death-censored Allograft Loss | From Baseline to 4 years | Time to death-censored allograft loss, was defined as occurrence of any of the following components: * eGFR \< 15 mL/min/1.73 m\^2\* * return to dialysis\* * allograft nephrectomy, or * retransplantation. (\*Total cumulative duration of sustained eGFR \< 15 mL/min/1.73 m\^2 AND / OR dialysis \>= 60 days.) If the eGFR \< 15 mL/min/1.73 m\^2 was the only component reached, the value must be sustained over at least 60 days and must be confirmed by a repeat measurement after \>= 60 days from the first measurement. The number of participants with death-censored allograft loss are reported here. |
| Percentage of Participants With Death-censored Allograft Loss | From Baseline to 4 years | Death-censored allograft loss was defined as the occurrence of any of the following components: * eGFR \< 15 mL/min/1.73 m\^2\* * return to dialysis\* * allograft nephrectomy, or * retransplantation. (\*Total cumulative duration of sustained eGFR \< 15 mL/min/1.73 m\^2 AND / OR dialysis \>= 60 days.) If the eGFR \< 15 mL/min/1.73 m\^2 was the only component reached, the value must be sustained over at least 60 days and must be confirmed by a repeat measurement after \>= 60 days from the first measurement. The percentage of participants who experienced death-censored allograft loss are reported here. |
| Change From Baseline in Urine Albumin Creatinine Ratio (UACR) | From Baseline to Week 52 | — |
| Percent Change From Baseline in Mean Fluorescent Intensity for Donor-Specific Antibodies (DSA) | From Baseline to Week 52 | — |
| Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | From Baseline to Week 52 | Banff lesion grading scores assess the presence and the degree of histopathological changes in the different compartments of kidney biopsies. Here, the improved category is defined as a decline in the Banff lesion grading score. Participants with improved scores, not improved scores, and missing biopsies for C4d staining, interstitial fibrosis, tubular atrophy, glomerular basement membrane double contours, glomerulitis and peritubular capillaritis are reported for this outcome measure. |
| Incidence of Acute Rejection Episodes of T Cell-mediated Rejection (TCMR) and Antibody-mediated Rejection (ABMR) | Baseline up to End of treatment (up to approximately 4 years) | Number of participants who had at least one acute rejection episode (TCMR or ABMR) are reported for this outcome measure. |
| Overall Participant Survival | Up to Week 52 | Number of participants who were alive up to Week 52 are reported for this outcome measure. |
Countries
Australia, Austria, Belgium, Canada, Czechia, France, Germany, Hungary, Netherlands, New Zealand, South Korea, Spain, Sweden, Taiwan, United States
Participant flow
Recruitment details
The study was conducted at 139 study sites in 13 countries: Canada, United States, Austria, Czechia, France, Germany, Hungary, Netherlands, Spain, Sweden, Switzerland, Democratic People's Republic of Korea, and Australia.
Pre-assignment details
A total of 382 participants were screened, of which 188 were screen failures. Of the screened participants, 194 were randomized in a 1:1 ratio to receive study interventions (Clazakizumab or Placebo).
Participants by arm
| Arm | Count |
|---|---|
| Clazakizumab Participants received clazakizumab via SC injection Q4W until the participant: permanently discontinued the IP, withdrew from the study, experienced allograft loss, died, or reached the CTED, whichever occurred first during this study. | 94 |
| Placebo Participants received Placebo via SC injection Q4W until the participant: permanently discontinued IP, withdrew from the study, experienced allograft loss, died, or reached the CTED, whichever occurred first during this study. | 100 |
| Total | 194 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other-unspecified | 4 | 1 |
| Overall Study | Physician Decision | 5 | 4 |
| Overall Study | Sponsor Decision (due to study termination) | 68 | 71 |
| Overall Study | Withdrew Consent | 1 | 8 |
Baseline characteristics
| Characteristic | Clazakizumab | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 46.3 years STANDARD_DEVIATION 11.87 | 47.0 years STANDARD_DEVIATION 12.24 | 46.7 years STANDARD_DEVIATION 12.04 |
| Race/Ethnicity, Customized Ethnicity Hispanic, Latino/a or of Spanish origin | 18 Participants | 16 Participants | 34 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic, Latino/a or of Spanish origin | 69 Participants | 78 Participants | 147 Participants |
| Race/Ethnicity, Customized Ethnicity Not reported | 5 Participants | 4 Participants | 9 Participants |
| Race/Ethnicity, Customized Ethnicity Unknown | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Race American or Alaskan Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian Indian | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Black or African American | 10 Participants | 7 Participants | 17 Participants |
| Race/Ethnicity, Customized Race Filipino | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Korean | 9 Participants | 13 Participants | 22 Participants |
| Race/Ethnicity, Customized Race Missing | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 6 Participants | 8 Participants | 14 Participants |
| Race/Ethnicity, Customized Race Other Asian | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Race White | 62 Participants | 69 Participants | 131 Participants |
| Sex: Female, Male Female | 29 Participants | 26 Participants | 55 Participants |
| Sex: Female, Male Male | 65 Participants | 74 Participants | 139 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 93 | 1 / 100 |
| other Total, other adverse events | 81 / 93 | 80 / 100 |
| serious Total, serious adverse events | 39 / 93 | 39 / 100 |
Outcome results
Primary
Change From Baseline to Week 52 in Estimated Glomerular Filtration Rate (eGFR)
This primary outcome measure was the one from the first interim analysis.
Time frame: From Baseline to Week 52
Population: Analysis was performed on the intent-to-treat (ITT) analysis set. The ITT analysis set consisted of all randomized participants who received at least 1 dose of study drug and who had a baseline assessment and at least 1 post baseline assessment of eGFR.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Clazakizumab | Change From Baseline to Week 52 in Estimated Glomerular Filtration Rate (eGFR) | -8.0 milliliter per minute per 1.73 meter^2 |
| Placebo | Change From Baseline to Week 52 in Estimated Glomerular Filtration Rate (eGFR) | -5.2 milliliter per minute per 1.73 meter^2 |
95% CI: [-5.84, 0.35]
Primary
Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV)
Number of participants who tested positive for BKV, CMV or EBV according to the maximum measured viral amount (International Units/mL \[IU/mL\]) after baseline are reported here.
Time frame: From baseline up to 4 years
Population: Analysis was performed on the SAS. The SAS consisted of all randomized participants who had received at least 1 dose of study drug. Here, 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Clazakizumab | Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) | BKV >=320 IU/mL to <3200 IU/mL | 1 Participants |
| Clazakizumab | Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) | CMV >=1000 IU/mL to <5000 IU/mL | 2 Participants |
| Clazakizumab | Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) | CMV >LLOQ to <1000 IU/mL | 5 Participants |
| Clazakizumab | Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) | EBV >LLOQ to <10200 IU/mL | 8 Participants |
| Clazakizumab | Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) | BKV >=3200 IU/mL | 1 Participants |
| Clazakizumab | Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) | EBV >=10200 IU/mL to <20400 IU/mL | 0 Participants |
| Clazakizumab | Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) | CMV >=5000 IU/mL | 0 Participants |
| Clazakizumab | Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) | EBV >=20400 IU/mL | 0 Participants |
| Clazakizumab | Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) | BKV >Lower limit of quantification (LLOQ) to <320 IU/mL | 3 Participants |
| Placebo | Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) | EBV >=20400 IU/mL | 0 Participants |
| Placebo | Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) | BKV >Lower limit of quantification (LLOQ) to <320 IU/mL | 2 Participants |
| Placebo | Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) | BKV >=320 IU/mL to <3200 IU/mL | 0 Participants |
| Placebo | Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) | CMV >LLOQ to <1000 IU/mL | 1 Participants |
| Placebo | Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) | CMV >=1000 IU/mL to <5000 IU/mL | 2 Participants |
| Placebo | Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) | CMV >=5000 IU/mL | 0 Participants |
| Placebo | Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) | BKV >=3200 IU/mL | 0 Participants |
| Placebo | Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) | EBV >LLOQ to <10200 IU/mL | 7 Participants |
| Placebo | Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) | EBV >=10200 IU/mL to <20400 IU/mL | 0 Participants |
Primary
Number of Participants With Abnormal Laboratory Test Results
Laboratory tests included liver function test (LFTs), complete blood count (CBC), plasma lipids, high-sensitivity C-reactive protein (hsCRP). Only participants with abnormal laboratory test results are reported here. Here, ULN = upper limit of normal, LLN = lower limit of normal, ALT = Alanine aminotransferase and AST = Aspartate aminotransferase.
Time frame: Up to 4 years
Population: Analysis was performed on the SAS. The SAS consisted of all randomized participants who had received at least 1 dose of study drug. Here, 'overall number of participants analyzed' = participants with evaluable data for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Clazakizumab | Number of Participants With Abnormal Laboratory Test Results | ALT : >ULN to 3 x ULN | 15 Participants |
| Clazakizumab | Number of Participants With Abnormal Laboratory Test Results | ALT : > 3 to 5 × ULN | 0 Participants |
| Clazakizumab | Number of Participants With Abnormal Laboratory Test Results | AST : >ULN to 3 x ULN | 11 Participants |
| Clazakizumab | Number of Participants With Abnormal Laboratory Test Results | Neutrophils: < 2.5 to 1.5 10^9/L | 33 Participants |
| Clazakizumab | Number of Participants With Abnormal Laboratory Test Results | Platelets: < LLN to 75.0 10^9/L | 39 Participants |
| Clazakizumab | Number of Participants With Abnormal Laboratory Test Results | Platelets: < 75.0 to 50.0 10^9/L | 1 Participants |
| Clazakizumab | Number of Participants With Abnormal Laboratory Test Results | AST : > 3 to 5 × ULN | 1 Participants |
| Clazakizumab | Number of Participants With Abnormal Laboratory Test Results | AST : > 5 × ULN | 0 Participants |
| Clazakizumab | Number of Participants With Abnormal Laboratory Test Results | Bilirubin: > ULN to 2 × ULN | 20 Participants |
| Clazakizumab | Number of Participants With Abnormal Laboratory Test Results | Bilirubin: > 2 × ULN | 5 Participants |
| Clazakizumab | Number of Participants With Abnormal Laboratory Test Results | Neutrophils: < 1.5 to 1.0 10^9/L | 15 Participants |
| Clazakizumab | Number of Participants With Abnormal Laboratory Test Results | Neutrophils: < 1.0 10^9/L | 7 Participants |
| Placebo | Number of Participants With Abnormal Laboratory Test Results | Neutrophils: < 1.5 to 1.0 10^9/L | 5 Participants |
| Placebo | Number of Participants With Abnormal Laboratory Test Results | ALT : >ULN to 3 x ULN | 6 Participants |
| Placebo | Number of Participants With Abnormal Laboratory Test Results | AST : > 3 to 5 × ULN | 0 Participants |
| Placebo | Number of Participants With Abnormal Laboratory Test Results | ALT : > 3 to 5 × ULN | 1 Participants |
| Placebo | Number of Participants With Abnormal Laboratory Test Results | Bilirubin: > 2 × ULN | 0 Participants |
| Placebo | Number of Participants With Abnormal Laboratory Test Results | AST : > 5 × ULN | 2 Participants |
| Placebo | Number of Participants With Abnormal Laboratory Test Results | Neutrophils: < 2.5 to 1.5 10^9/L | 21 Participants |
| Placebo | Number of Participants With Abnormal Laboratory Test Results | Neutrophils: < 1.0 10^9/L | 0 Participants |
| Placebo | Number of Participants With Abnormal Laboratory Test Results | Platelets: < LLN to 75.0 10^9/L | 10 Participants |
| Placebo | Number of Participants With Abnormal Laboratory Test Results | Bilirubin: > ULN to 2 × ULN | 6 Participants |
| Placebo | Number of Participants With Abnormal Laboratory Test Results | Platelets: < 75.0 to 50.0 10^9/L | 0 Participants |
| Placebo | Number of Participants With Abnormal Laboratory Test Results | AST : >ULN to 3 x ULN | 4 Participants |
Primary
Number of Participants With Clinically Significant Change in Vital Signs, Electrocardiograms (ECGs), and Physical Examination
Time frame: Up to 4 years
Population: Analysis was performed on the SAS. The SAS consisted of all randomized participants who had received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Clazakizumab | Number of Participants With Clinically Significant Change in Vital Signs, Electrocardiograms (ECGs), and Physical Examination | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Change in Vital Signs, Electrocardiograms (ECGs), and Physical Examination | 0 Participants |
Primary
Number of Participants With Composite All-cause Allograft Loss or Irreversible Loss of Allograft Function
Composite all-cause allograft loss or irreversible loss of allograft function, defined as time to first occurrence of any of the following components: * eGFR \< 15 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2)\* * return to dialysis\* * allograft nephrectomy * retransplantation * death from any cause, or * a sustained (greater than or equal to \[\>=\] 60 days) 40% decline in eGFR from Baseline. (\*Total cumulative duration of sustained eGFR \< 15 mL/min/1.73 m\^2 AND / OR dialysis \>= 60 days.) If the eGFR \< 15 mL/min/1.73 m\^2 was the only component reached, the value must be sustained over at least 60 days and must be confirmed by a repeat measurement after \>= 60 days from the first measurement. The number of participants with composite all-cause allograft loss or irreversible loss of allograft function are reported here. Time-to-event data were not calculated due to the study's termination.
Time frame: From Baseline to 4 years
Population: Analysis was performed on the ITT analysis set. The ITT analysis set consisted of all participants who received at least 1 dose of study drug and who had a baseline assessment and at least 1 post baseline assessment of eGFR.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Clazakizumab | Number of Participants With Composite All-cause Allograft Loss or Irreversible Loss of Allograft Function | 26 Participants |
| Placebo | Number of Participants With Composite All-cause Allograft Loss or Irreversible Loss of Allograft Function | 22 Participants |
Primary
Number of Participants With Positive Anti-drug Antibodies
Time frame: Baseline, Weeks 12, 24, and 48
Population: Analysis was performed on the SAS. The SAS consisted of all randomized participants who had received at least 1 dose of study drug. Here, 'overall number of participants' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Clazakizumab | Number of Participants With Positive Anti-drug Antibodies | Baseline | 5 Participants |
| Clazakizumab | Number of Participants With Positive Anti-drug Antibodies | Week 12 | 3 Participants |
| Clazakizumab | Number of Participants With Positive Anti-drug Antibodies | Week 24 | 2 Participants |
| Clazakizumab | Number of Participants With Positive Anti-drug Antibodies | Week 48 | 0 Participants |
| Placebo | Number of Participants With Positive Anti-drug Antibodies | Week 48 | 4 Participants |
| Placebo | Number of Participants With Positive Anti-drug Antibodies | Baseline | 10 Participants |
| Placebo | Number of Participants With Positive Anti-drug Antibodies | Week 24 | 7 Participants |
| Placebo | Number of Participants With Positive Anti-drug Antibodies | Week 12 | 8 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs)
Time frame: Up to 4 years
Population: Analysis was performed on the safety analysis set (SAS). The SAS consisted of all randomized participants who had received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Clazakizumab | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs) | TEAEs | 89 Participants |
| Clazakizumab | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs) | Serious TEAEs | 39 Participants |
| Clazakizumab | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs) | AESIs | 56 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs) | TEAEs | 88 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs) | Serious TEAEs | 39 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs) | AESIs | 52 Participants |
Primary
Percentage of Participants With Abnormal Laboratory Test Results
Laboratory tests included LFTs, CBC, plasma lipids, hsCRP. Only percentage of participants with abnormal laboratory test results are reported here. Here, ULN = upper limit of normal, LLN = lower limit of normal, ALT = Alanine aminotransferase and AST = Aspartate aminotransferase.
Time frame: Up to 4 years
Population: Analysis was performed on the SAS. The SAS consisted of all randomized participants who had received at least 1 dose of study drug. Here, 'overall number of participants analyzed' = participants with evaluable data for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clazakizumab | Percentage of Participants With Abnormal Laboratory Test Results | Platelets: < LLN to 75.0 10^9/L | 41.9 percentage of participants |
| Clazakizumab | Percentage of Participants With Abnormal Laboratory Test Results | AST : >ULN to 3 x ULN | 11.8 percentage of participants |
| Clazakizumab | Percentage of Participants With Abnormal Laboratory Test Results | AST : > 5 × ULN | 0 percentage of participants |
| Clazakizumab | Percentage of Participants With Abnormal Laboratory Test Results | Platelets: < 75.0 to 50.0 10^9/L | 1.1 percentage of participants |
| Clazakizumab | Percentage of Participants With Abnormal Laboratory Test Results | Bilirubin: > ULN to 2 × ULN | 21.5 percentage of participants |
| Clazakizumab | Percentage of Participants With Abnormal Laboratory Test Results | Neutrophils: < 2.5 to 1.5 10^9/L | 35.5 percentage of participants |
| Clazakizumab | Percentage of Participants With Abnormal Laboratory Test Results | Bilirubin: > 2 × ULN | 5.4 percentage of participants |
| Clazakizumab | Percentage of Participants With Abnormal Laboratory Test Results | AST : > 3 to 5 × ULN | 1.1 percentage of participants |
| Clazakizumab | Percentage of Participants With Abnormal Laboratory Test Results | Neutrophils: < 1.5 to 1.0 10^9/L | 16.1 percentage of participants |
| Clazakizumab | Percentage of Participants With Abnormal Laboratory Test Results | ALT : > 3 to 5 × ULN | 0 percentage of participants |
| Clazakizumab | Percentage of Participants With Abnormal Laboratory Test Results | Neutrophils: < 1.0 10^9/L | 7.5 percentage of participants |
| Clazakizumab | Percentage of Participants With Abnormal Laboratory Test Results | ALT : >ULN to 3 x ULN | 16.1 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Laboratory Test Results | Neutrophils: < 1.0 10^9/L | 0 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Laboratory Test Results | AST : > 3 to 5 × ULN | 0 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Laboratory Test Results | Neutrophils: < 2.5 to 1.5 10^9/L | 21.2 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Laboratory Test Results | Platelets: < LLN to 75.0 10^9/L | 10.1 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Laboratory Test Results | Platelets: < 75.0 to 50.0 10^9/L | 0 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Laboratory Test Results | ALT : >ULN to 3 x ULN | 6.1 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Laboratory Test Results | ALT : > 3 to 5 × ULN | 1.0 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Laboratory Test Results | AST : >ULN to 3 x ULN | 4.0 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Laboratory Test Results | AST : > 5 × ULN | 2.0 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Laboratory Test Results | Bilirubin: > ULN to 2 × ULN | 6.1 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Laboratory Test Results | Bilirubin: > 2 × ULN | 0 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Laboratory Test Results | Neutrophils: < 1.5 to 1.0 10^9/L | 5.1 percentage of participants |
Primary
Percentage of Participants With Composite All-cause Allograft Loss or Irreversible Loss of Allograft Function
Composite all-cause allograft loss or irreversible loss of allograft function, defined as time to first occurrence of any of the following components: * eGFR \< 15 mL/min/1.73 m\^2\* * return to dialysis\* * allograft nephrectomy * retransplantation * death from any cause, or * a sustained (greater than or equal to \[\>=\] 60 days) 40% decline in eGFR from Baseline. (\*Total cumulative duration of sustained eGFR \< 15 mL/min/1.73 m\^2 AND / OR dialysis \>= 60 days.) If the eGFR \< 15 mL/min/1.73 m\^2 was the only component reached, the value must be sustained over at least 60 days and must be confirmed by a repeat measurement after \>= 60 days from the first measurement. The percentage of participants with composite all-cause allograft loss or irreversible loss of allograft function are reported here.
Time frame: From Baseline to 4 years
Population: Analysis was performed on the ITT analysis set. The ITT analysis set consisted of all participants who received at least 1 dose of study drug and who had a baseline assessment and at least 1 post baseline assessment of eGFR.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clazakizumab | Percentage of Participants With Composite All-cause Allograft Loss or Irreversible Loss of Allograft Function | 28.3 percentage of participants |
| Placebo | Percentage of Participants With Composite All-cause Allograft Loss or Irreversible Loss of Allograft Function | 22.2 percentage of participants |
Primary
Percentage of Participants With Positive Anti-drug Antibodies
Time frame: Baseline, Weeks 12, 24, and 48
Population: Analysis was performed on the SAS. The SAS consisted of all randomized participants who had received at least 1 dose of study drug. Here, 'overall number of participants' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clazakizumab | Percentage of Participants With Positive Anti-drug Antibodies | Baseline | 5.7 percentage of participants |
| Clazakizumab | Percentage of Participants With Positive Anti-drug Antibodies | Week 12 | 4.1 percentage of participants |
| Clazakizumab | Percentage of Participants With Positive Anti-drug Antibodies | Week 24 | 2.9 percentage of participants |
| Clazakizumab | Percentage of Participants With Positive Anti-drug Antibodies | Week 48 | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-drug Antibodies | Week 48 | 7.7 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-drug Antibodies | Baseline | 10.3 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-drug Antibodies | Week 24 | 9.7 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-drug Antibodies | Week 12 | 9.8 percentage of participants |
Primary
Percentage of Participants With TEAEs, Serious TEAEs, and AESIs
Time frame: Up to 4 years
Population: Analysis was performed on the SAS. The SAS consisted of all randomized participants who had received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clazakizumab | Percentage of Participants With TEAEs, Serious TEAEs, and AESIs | TEAEs | 95.7 percentage of participants |
| Clazakizumab | Percentage of Participants With TEAEs, Serious TEAEs, and AESIs | Serious TEAEs | 41.9 percentage of participants |
| Clazakizumab | Percentage of Participants With TEAEs, Serious TEAEs, and AESIs | AESIs | 60.2 percentage of participants |
| Placebo | Percentage of Participants With TEAEs, Serious TEAEs, and AESIs | TEAEs | 88.0 percentage of participants |
| Placebo | Percentage of Participants With TEAEs, Serious TEAEs, and AESIs | Serious TEAEs | 39.0 percentage of participants |
| Placebo | Percentage of Participants With TEAEs, Serious TEAEs, and AESIs | AESIs | 52.0 percentage of participants |
Secondary
Area Under the Concentration-time Curve (AUC0-tau) at Steady State of CSL300
A subset of participants (out of the enrolled participants in the main study) had the option to participate in a PK/PD sub-study.
Time frame: Up to Week 24
Population: Analysis was performed on the PK/PD analysis set. The PK/PD substudy analysis set consisted of all participants in the SAS who consented to be a part of the PK / PD substudy and had at least 1 quantifiable PK concentration of investigational product after administration. Here, overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Clazakizumab | Area Under the Concentration-time Curve (AUC0-tau) at Steady State of CSL300 | 78080.34636 days*nanograms per milliliter | Geometric Coefficient of Variation 7.19614 |
Secondary
Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies
Banff lesion grading scores assess the presence and the degree of histopathological changes in the different compartments of kidney biopsies. Here, the improved category is defined as a decline in the Banff lesion grading score. Participants with improved scores, not improved scores, and missing biopsies for C4d staining, interstitial fibrosis, tubular atrophy, glomerular basement membrane double contours, glomerulitis and peritubular capillaritis are reported for this outcome measure.
Time frame: From Baseline to Week 52
Population: Analysis was performed on the ITT analysis set. The ITT analysis set consisted of all randomized participants who received at least 1 dose of the investigational product, had a Baseline assessment, and had at least 1 post-baseline assessment of eGFR.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Clazakizumab | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | C4d Staining | Missing biopsies | 65 Participants |
| Clazakizumab | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Peritubular Capillaritis | Improved score | 14 Participants |
| Clazakizumab | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Tubular Atrophy | Not improved score | 26 Participants |
| Clazakizumab | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Glomerular Basement Membrane Double Contours | Improved score | 6 Participants |
| Clazakizumab | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Peritubular Capillaritis | Missing biopsies | 65 Participants |
| Clazakizumab | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | C4d Staining | Not improved score | 17 Participants |
| Clazakizumab | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Interstitial Fibrosis | Not improved score | 24 Participants |
| Clazakizumab | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Interstitial Fibrosis | Missing biopsies | 65 Participants |
| Clazakizumab | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Interstitial Fibrosis | Improved score | 3 Participants |
| Clazakizumab | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Tubular Atrophy | Missing biopsies | 65 Participants |
| Clazakizumab | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Glomerulitis | Improved score | 14 Participants |
| Clazakizumab | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Glomerular Basement Membrane Double Contours | Not improved score | 21 Participants |
| Clazakizumab | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Tubular Atrophy | Improved score | 1 Participants |
| Clazakizumab | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Glomerular Basement Membrane Double Contours | Missing biopsies | 65 Participants |
| Clazakizumab | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Glomerulitis | Missing biopsies | 65 Participants |
| Clazakizumab | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Glomerulitis | Not improved score | 13 Participants |
| Clazakizumab | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Peritubular Capillaritis | Not improved score | 13 Participants |
| Clazakizumab | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | C4d Staining | Improved score | 10 Participants |
| Placebo | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Peritubular Capillaritis | Missing biopsies | 68 Participants |
| Placebo | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | C4d Staining | Improved score | 10 Participants |
| Placebo | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | C4d Staining | Not improved score | 21 Participants |
| Placebo | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | C4d Staining | Missing biopsies | 68 Participants |
| Placebo | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Interstitial Fibrosis | Improved score | 8 Participants |
| Placebo | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Interstitial Fibrosis | Missing biopsies | 68 Participants |
| Placebo | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Tubular Atrophy | Improved score | 5 Participants |
| Placebo | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Glomerular Basement Membrane Double Contours | Improved score | 10 Participants |
| Placebo | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Glomerular Basement Membrane Double Contours | Missing biopsies | 68 Participants |
| Placebo | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Glomerulitis | Not improved score | 14 Participants |
| Placebo | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Glomerulitis | Missing biopsies | 68 Participants |
| Placebo | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Peritubular Capillaritis | Improved score | 15 Participants |
| Placebo | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Peritubular Capillaritis | Not improved score | 16 Participants |
| Placebo | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Interstitial Fibrosis | Not improved score | 23 Participants |
| Placebo | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Tubular Atrophy | Not improved score | 26 Participants |
| Placebo | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Tubular Atrophy | Missing biopsies | 68 Participants |
| Placebo | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Glomerular Basement Membrane Double Contours | Not improved score | 21 Participants |
| Placebo | Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies | Glomerulitis | Improved score | 17 Participants |
Secondary
Change From Baseline in Urine Albumin Creatinine Ratio (UACR)
Time frame: From Baseline to Week 52
Population: Analysis was performed on the SAS. The SAS consisted of all randomized participants who had received at least 1 dose of study drug. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clazakizumab | Change From Baseline in Urine Albumin Creatinine Ratio (UACR) | 50.734 gram per mole | Standard Deviation 125.5628 |
| Placebo | Change From Baseline in Urine Albumin Creatinine Ratio (UACR) | 31.178 gram per mole | Standard Deviation 112.8894 |
Secondary
Incidence of Acute Rejection Episodes of T Cell-mediated Rejection (TCMR) and Antibody-mediated Rejection (ABMR)
Number of participants who had at least one acute rejection episode (TCMR or ABMR) are reported for this outcome measure.
Time frame: Baseline up to End of treatment (up to approximately 4 years)
Population: Analysis was performed on the ITT analysis set. The ITT analysis set consisted of all randomized participants who received at least 1 dose of study drug and who had a baseline assessment and at least 1 post baseline assessment of eGFR.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Clazakizumab | Incidence of Acute Rejection Episodes of T Cell-mediated Rejection (TCMR) and Antibody-mediated Rejection (ABMR) | 2 Participants |
| Placebo | Incidence of Acute Rejection Episodes of T Cell-mediated Rejection (TCMR) and Antibody-mediated Rejection (ABMR) | 3 Participants |
Secondary
Maximum Concentration at Steady State (Cmax ss) of CSL300
A subset of participants (out of the enrolled participants in the main study) had the option to participate in a pharmacokinetic (PK)/ Pharmacodynamic (PD) sub-study.
Time frame: Up to Week 24
Population: Analysis was performed on the PK/ PD analysis set. The PK/PD substudy analysis set consisted of all participants in the SAS who consented to be a part of the PK / PD substudy and had at least 1 quantifiable PK concentration of investigational product after administration. Here, overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Clazakizumab | Maximum Concentration at Steady State (Cmax ss) of CSL300 | 3556.8 nanograms per milliliter | Geometric Coefficient of Variation 10.5 |
Secondary
Number of Participants With Composite All-cause Allograft Loss
Composite all-cause allograft loss, defined as, time to first occurrence of any of the following components: * eGFR \< 15 mL/min/1.73 m\^2\* * return to dialysis\* * allograft nephrectomy * retransplantation, or * death from any cause. (\*Total cumulative duration of sustained eGFR \< 15 mL/min/1.73 m\^2 AND / OR dialysis \>= 60 days.) If the eGFR \< 15 mL/min/1.73 m\^2 was the only component reached, the value must be sustained over at least 60 days and must be confirmed by a repeat measurement after \>= 60 days from the first measurement. The number of participants with composite all-cause allograft loss are reported here.
Time frame: From Baseline to 4 years
Population: Analysis was performed on the ITT analysis set. The ITT analysis set consisted of all participants who received at least 1 dose of study drug and who had a baseline assessment and at least 1 post baseline assessment of eGFR.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Clazakizumab | Number of Participants With Composite All-cause Allograft Loss | 17 Participants |
| Placebo | Number of Participants With Composite All-cause Allograft Loss | 14 Participants |
Secondary
Number of Participants With Death-censored Allograft Loss
Time to death-censored allograft loss, was defined as occurrence of any of the following components: * eGFR \< 15 mL/min/1.73 m\^2\* * return to dialysis\* * allograft nephrectomy, or * retransplantation. (\*Total cumulative duration of sustained eGFR \< 15 mL/min/1.73 m\^2 AND / OR dialysis \>= 60 days.) If the eGFR \< 15 mL/min/1.73 m\^2 was the only component reached, the value must be sustained over at least 60 days and must be confirmed by a repeat measurement after \>= 60 days from the first measurement. The number of participants with death-censored allograft loss are reported here.
Time frame: From Baseline to 4 years
Population: Analysis was performed on the ITT analysis set. The ITT analysis set consisted of all participants who received at least 1 dose of study drug and who had a baseline assessment and at least 1 post baseline assessment of eGFR.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Clazakizumab | Number of Participants With Death-censored Allograft Loss | 16 Participants |
| Placebo | Number of Participants With Death-censored Allograft Loss | 13 Participants |
Secondary
Number of Participants With Irreversible Loss of Allograft Function
Irreversible loss of allograft function as defined by a 40% decline in eGFR from Baseline sustained for at least 60 days.
Time frame: From Baseline to 4 years
Population: Analysis was performed on the ITT analysis set. The ITT analysis set consisted of all participants who received at least 1 dose of study drug and who had a baseline assessment and at least 1 post baseline assessment of eGFR.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Clazakizumab | Number of Participants With Irreversible Loss of Allograft Function | 22 Participants |
| Placebo | Number of Participants With Irreversible Loss of Allograft Function | 18 Participants |
Secondary
Overall Participant Survival
Number of participants who were alive up to Week 52 are reported for this outcome measure.
Time frame: Up to Week 52
Population: Analysis was performed on the ITT analysis set. The ITT analysis set consisted of all randomized participants who received at least 1 dose of the investigational product, had a Baseline assessment, and had at least 1 post-baseline assessment of eGFR.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Clazakizumab | Overall Participant Survival | 90 Participants |
| Placebo | Overall Participant Survival | 98 Participants |
Secondary
Percentage of Participants With Composite All-cause Allograft Loss
Composite all-cause allograft loss, defined as, time to first occurrence of any of the following components: * eGFR \< 15 mL/min/1.73 m\^2\* * return to dialysis\* * allograft nephrectomy * retransplantation, or * death from any cause. (\*Total cumulative duration of sustained eGFR \< 15 mL/min/1.73 m\^2 AND / OR dialysis \>= 60 days.) If the eGFR \< 15 mL/min/1.73 m\^2 was the only component reached, the value must be sustained over at least 60 days and must be confirmed by a repeat measurement after \>= 60 days from the first measurement. The percentage of participants with composite all-cause allograft loss are reported here.
Time frame: From Baseline to 4 years
Population: Analysis was performed on the ITT analysis set. The ITT analysis set consisted of all participants who received at least 1 dose of study drug and who had a baseline assessment and at least 1 post baseline assessment of eGFR.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clazakizumab | Percentage of Participants With Composite All-cause Allograft Loss | 18.5 percentage of participants |
| Placebo | Percentage of Participants With Composite All-cause Allograft Loss | 14.1 percentage of participants |
Secondary
Percentage of Participants With Death-censored Allograft Loss
Death-censored allograft loss was defined as the occurrence of any of the following components: * eGFR \< 15 mL/min/1.73 m\^2\* * return to dialysis\* * allograft nephrectomy, or * retransplantation. (\*Total cumulative duration of sustained eGFR \< 15 mL/min/1.73 m\^2 AND / OR dialysis \>= 60 days.) If the eGFR \< 15 mL/min/1.73 m\^2 was the only component reached, the value must be sustained over at least 60 days and must be confirmed by a repeat measurement after \>= 60 days from the first measurement. The percentage of participants who experienced death-censored allograft loss are reported here.
Time frame: From Baseline to 4 years
Population: Analysis was performed on the ITT analysis set. The ITT analysis set consisted of all randomized participants who received at least 1 dose of the investigational product, had a Baseline assessment, and had at least 1 post-baseline assessment of eGFR.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clazakizumab | Percentage of Participants With Death-censored Allograft Loss | 17.4 percentage of participants |
| Placebo | Percentage of Participants With Death-censored Allograft Loss | 13.1 percentage of participants |
Secondary
Percentage of Participants With Irreversible Loss of Allograft Function
Irreversible loss of allograft function as defined by a 40% decline in eGFR from Baseline sustained for at least 60 days.
Time frame: From Baseline to 4 years
Population: Analysis was performed on the ITT analysis set. The ITT analysis set consisted of all participants who received at least 1 dose of study drug and who had a baseline assessment and at least 1 post baseline assessment of eGFR.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clazakizumab | Percentage of Participants With Irreversible Loss of Allograft Function | 23.9 percentage of participants |
| Placebo | Percentage of Participants With Irreversible Loss of Allograft Function | 18.2 percentage of participants |
Secondary
Percent Change From Baseline in Mean Fluorescent Intensity for Donor-Specific Antibodies (DSA)
Time frame: From Baseline to Week 52
Population: Analysis was performed on the SAS. The SAS consisted of all randomized participants who had received at least 1 dose of study drug. The Overall Number of Participants Analyzed reported here reflects all participants who were analyzed, which includes all (N = 93 Clazakizumab and 100 Placebo) participants assessed at baseline to determine DSA class I or II. Here, 'Number Analyzed' = the number of participants in Class I or II classified at baseline who had available MFI data at Week 52.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Clazakizumab | Percent Change From Baseline in Mean Fluorescent Intensity for Donor-Specific Antibodies (DSA) | DSA Class II | -27.15 percent change |
| Clazakizumab | Percent Change From Baseline in Mean Fluorescent Intensity for Donor-Specific Antibodies (DSA) | DSA Class I | -23.20 percent change |
| Placebo | Percent Change From Baseline in Mean Fluorescent Intensity for Donor-Specific Antibodies (DSA) | DSA Class II | -13.68 percent change |
| Placebo | Percent Change From Baseline in Mean Fluorescent Intensity for Donor-Specific Antibodies (DSA) | DSA Class I | -39.71 percent change |
Secondary
Time of Maximum Concentration at Steady State (Tmax ss) of CSL300
A subset of participants (out of the enrolled participants in the main study) had the option to participate in a PK/PD sub-study.
Time frame: Up to Week 24
Population: Analysis was performed on the PK/PD analysis set. The PK/PD substudy analysis set consisted of all participants in the SAS who consented to be a part of the PK / PD substudy and had at least 1 quantifiable PK concentration of investigational product after administration. Here, overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clazakizumab | Time of Maximum Concentration at Steady State (Tmax ss) of CSL300 | 6.92292 day |
Secondary
Trough Concentrations at Steady State (Ctrough ss) of CSL300
A subset of participants (out of the enrolled participants in the main study) had the option to participate in a PK/PD sub-study.
Time frame: Up to Week 24
Population: Analysis was performed on the PK/PD analysis set. The PK/PD substudy analysis set consisted of all participants in the SAS who consented to be a part of the PK / PD substudy and had at least 1 quantifiable PK concentration of investigational product after administration. Here, overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Clazakizumab | Trough Concentrations at Steady State (Ctrough ss) of CSL300 | 2366.8 nanograms per milliliter | Geometric Coefficient of Variation 9.2 |