A Prospective, Observational Long-term Follow-up Trial of Kidney Transplant Patients Treated With Imlifidase or Plasma Exchange After an Active/Chronic Active Antibody-Mediated Rejection Episode
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 7
- 主要终点
- Overall Graft Survival at Year 3
研究概览
简要总结
The aim of this trial is to collect data and provide a better understanding of the long-term outcome of imlifidase treatment on active or chronic active antibody-mediated rejection (AMR) in kidney transplant recipients. This is done by collecting data during an extended follow-up period of 3 years of clinical study trial 16-HMedIdeS-12, in which patients received either imlifidase or plasma exchange (PE) as AMR treatment. Data for parameters such as kidney graft survival, patient survival, kidney function, treatment of rebound of donor specific antibodies (DSA) and anti-drug antibodies (ADAs) are collected.
详细描述
AMR is one of the most challenging adverse events following kidney transplantation and a major cause of graft dysfunction and graft loss. AMR is triggered by donor-specific antibodies (DSA).Transplant glomerulopathy is a known consequence of persistent DSA positivity which results in graft failure and return to dialysis with attendant consequences for the patient and financial costs for the health care system.
The time from transplantation to onset of clinical symptoms of AMR varies largely between individuals. An early AMR (<30 days post-transplant) is commonly classified as active AMR and most often triggered by an immunological recall response with pre-existing DSA. A late AMR (>30 days post-transplant) is classified as either active or chronic active AMR and is caused by either a recall DSA response or newly developing naïve immune response associated with de novo DSA production.
There is no currently approved therapy for AMR and patients are often treated with a combination of therapies i.e., high dose IVIg +/- rituximab, PE with low dose IVIg +/- rituximab, and eculizumab which makes analysis of efficacy of any single agent difficult. Hence, there is a large unmet clinical need for new therapies to treat AMR.
Imlifidase is an IgG-degrading enzyme of Streptococcus pyogenes that cleaves all four human subclasses of IgG with high efficacy and specificity. The rapidity of the IgG cleavage by imlifidase is considered a major advantage as compared with PE, which often requires several rounds over several days to achieve a sufficient DSA reduction. Within a few hours after imlifidase dosing, the entire pool of IgG is completely cleaved and thereby a window where IgG levels are kept very low for approximately one week is created.
The short-term efficacy and safety of imlifidase in active and chronic active AMR is being investigated in a randomized, open-label, multi-centre trial, using PE as an active control (i.e. the feeder study: 16-HMedIdeS-12). A total of 30 subjects will be included in this study (20 in the imlifidase arm and 10 in the plasma exchange arm). The primary objective is to investigate the efficacy of imlifidase in removing DSA in patients who are experiencing an AMR episode after kidney transplantation.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed Informed Consent obtained before any trial-related procedures
- •Willingness and ability to comply with the protocol
- •Previous treatment with imlifidase or plasma exchange in the trial 16-HMedIdeS-12
- •Note: The primary objective of this trial is overall graft survival after treatment with imlifidase or plasma exchange. Therefore, subjects can also be included even if the subject did not fully complete the feeder trial follow up but was dosed with imlifidase or plasma exchange in the trial 16-HMedIdeS-12.
排除标准
- •Inability by the judgement of the investigator to participate in the trial for any other reason
研究组 & 干预措施
Imlifidase treatment in feeder Study 16-HMedIdeS-12
No treatment is given in this long-term follow-up study. In the feeder study (16-HMedIdeS-12) the patients in this group were treated with imlifidase.
干预措施: Imlifidase (Drug)
结局指标
主要结局
Overall Graft Survival at Year 3
时间窗: 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12)
Graft survival is defined as time from start of AMR treatment in feeder study (16-HMedIdeS-12) to graft loss. Graft loss is defined as permanent return to dialysis for at least 6 weeks, re-transplantation, or nephrectomy. Data table show number of patients with a functioning graft at Year 3.
次要结局
- ADA Levels(1,2 and 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12))
- Overall Graft Survival at Year 2(2 years after start of AMR treatment in feeder study (16-HMedIdeS-12))
- Overall Graft Survival at Year 1(1 year after start of AMR treatment in feeder study (16-HMedIdeS-12))
- Patient Survival at Year 3(3 years after start of AMR treatment in feeder study (16-HMedIdeS-12))
- Kidney Function as Evaluated by eGFR(1, 2 and 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12))
- Kidney Function as Evaluated by S/P-creatinine(1, 2 and 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12))
- Number of Participants With Presumed or Biopsy Proven AMR Episodes(3 years after start of AMR treatment in feeder study (16-HMedIdeS-12))
- Number of Participants With Presumed or Biopsy-proven Rejection Episodes (Other Than AMR Episodes)(3 years after start of AMR treatment in feeder study (16-HMedIdeS-12))
- DSA Levels(1, 2 and 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12))