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
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- CSL Behring
- 入组人数
- 194
- 试验地点
- 138
- 主要终点
- Change From Baseline to Week 52 in Estimated Glomerular Filtration Rate (eGFR)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Clazakizumab
Clazakizumab is a genetically engineered humanized immunoglobulin G1 (IgG1) mAb that binds to human IL-6 that is administered subcutaneously.
干预措施: Clazakizumab (Biological)
Placebo
Physiologic saline solution that is administered subcutaneously.
干预措施: Physiologic saline solution (Drug)
结局指标
主要结局
Change From Baseline to Week 52 in Estimated Glomerular Filtration Rate (eGFR)
时间窗: 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
时间窗: 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
时间窗: 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 Positive Anti-drug Antibodies
时间窗: Baseline, Weeks 12, 24, and 48
Percentage of Participants With Positive Anti-drug Antibodies
时间窗: Baseline, Weeks 12, 24, and 48
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs)
时间窗: Up to 4 years
Percentage of Participants With TEAEs, Serious TEAEs, and AESIs
时间窗: Up to 4 years
Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV)
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: Up to 4 years
次要结局
- Number of Participants With Irreversible Loss of Allograft Function(From Baseline to 4 years)
- Number of Participants With Composite All-cause Allograft Loss(From Baseline to 4 years)
- Percentage of Participants With Composite All-cause Allograft Loss(From Baseline to 4 years)
- Percentage of Participants With Irreversible Loss of Allograft Function(From Baseline to 4 years)
- Number of Participants With Death-censored Allograft Loss(From Baseline to 4 years)
- Percentage of Participants With Death-censored Allograft Loss(From Baseline to 4 years)
- 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)
- 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))
- Overall Participant Survival(Up to Week 52)
- Maximum Concentration at Steady State (Cmax ss) of CSL300(Up to Week 24)
- Trough Concentrations at Steady State (Ctrough ss) of CSL300(Up to Week 24)
- Area Under the Concentration-time Curve (AUC0-tau) at Steady State of CSL300(Up to Week 24)
- Time of Maximum Concentration at Steady State (Tmax ss) of CSL300(Up to Week 24)