Transplant Institute, Sahlgrenska University Hospital, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, 413 45, Gothenburg, Sweden.
Department of Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden.
Trials. 2024 Mar 22;25(1):213. doi: 10.1186/s13063-024-08020-0.
Chronic active antibody-mediated rejection (caAMR) in kidney transplants is associated with irreversible tissue damage and a leading cause of graft loss in the long-term. However, the treatment for caAMR remains a challenge to date. Recently, tocilizumab, a recombinant humanized monoclonal antibody directed against the human interleukin-6 (IL-6) receptor, has shown promise in the treatment of caAMR. However, it has not been systematically investigated so far underscoring the need for randomized controlled studies in this area.
The INTERCEPT study is an investigator-driven randomized controlled open-label multi-center trial in kidney transplant recipients to assess the efficacy of tocilizumab in the treatment of biopsy-proven caAMR. A total of 50 recipients with biopsy-proven caAMR at least 12 months after transplantation will be randomized to receive either tocilizumab (n = 25) added to our standard of care (SOC) maintenance treatment or SOC alone (n = 25) for a period of 24 months. Patients will be followed for an additional 12 months after cessation of study medication. After the inclusion biopsies at baseline, protocol kidney graft biopsies will be performed at 12 and 24 months. The sample size calculation assumed a difference of 5 ml/year in slope of estimated glomerular filtration rate (eGFR) between the two groups for 80% power at an alpha of 0.05. The primary endpoint is the slope of eGFR at 24 months after start of treatment. The secondary endpoints include assessment of the following at 12, 24, and 36 months: composite risk score iBox, safety, evolution and characteristics of donor-specific antibodies (DSA), graft histology, proteinuria, kidney function assessed by measured GFR (mGFR), patient- and death-censored graft survival, and patient-reported outcomes that include transplant-specific well-being, adherence to immunosuppressive medications and perceived threat of the risk of graft rejection.
No effective treatment exists for caAMR at present. Based on the hypothesis that inhibition of IL-6 receptor by tocilizumab will reduce antibody production and reduce antibody-mediated damage, our randomized trial has a potential to provide evidence for a novel treatment strategy for caAMR, therewith slowing the decline in graft function in the long-term.
ClinicalTrials.gov NCT04561986. Registered on September 24, 2020.
慢性活动性抗体介导的排斥反应（caAMR）在肾移植中与不可逆的组织损伤有关，是长期内移植物丢失的主要原因。然而，caAMR 的治疗仍然是一个挑战。最近，托珠单抗，一种针对人白细胞介素 6（IL-6）受体的重组人源化单克隆抗体，在 caAMR 的治疗中显示出了希望。然而，迄今为止，尚未对此进行系统研究，这突显了在该领域进行随机对照研究的必要性。
INTERCEPT 研究是一项由研究者驱动的、随机对照的开放性多中心临床试验，旨在评估托珠单抗治疗移植后至少 12 个月活检证实的 caAMR 的疗效。总共将有 50 名接受过移植的患者，在活检证实 caAMR 后至少 12 个月，将被随机分配接受托珠单抗（n = 25）加我们的标准治疗（SOC）维持治疗或 SOC 单药治疗（n = 25），为期 24 个月。患者将在停止研究药物后再随访 12 个月。在基线纳入活检后，将在 12 个月和 24 个月时进行方案性肾移植活检。样本量计算假设两组在治疗开始后 24 个月时估算肾小球滤过率（eGFR）斜率的差异为 5ml/年，在 80%的功效和 0.05 的 α 值下。主要终点是治疗开始后 24 个月时 eGFR 的斜率。次要终点包括在 12、24 和 36 个月时评估以下指标：复合风险评分 iBox、安全性、供体特异性抗体（DSA）的演变和特征、移植肾组织学、蛋白尿、通过测量肾小球滤过率（mGFR）评估的肾功能、患者和死亡censored 移植物存活率以及包括移植特异性幸福感、免疫抑制剂药物依从性和对移植物排斥风险的感知威胁在内的患者报告结果。
目前尚无有效的 caAMR 治疗方法。基于托珠单抗抑制 IL-6 受体将减少抗体产生并减少抗体介导的损伤的假设，我们的随机试验有可能为 caAMR 的新型治疗策略提供证据，从而减缓长期内移植物功能的下降。
ClinicalTrials.gov NCT04561986。注册于 2020 年 9 月 24 日。
