A Single-arm, Multi-centre Trial to Evaluate Efficacy and Safety of Imlifidase in Highly Sensitised Children (1-17 Years) Receiving a Kidney Transplant With Positive Crossmatch Against a Living or Deceased Donor Converted to Negative After Imlifidase Treatment
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 10
- 主要终点
- Proportion of patients with conversion of a positive crossmatch test to negative within 24 hours after start of imlifidase treatment
研究概览
简要总结
The goal of this clinical trial is to learn about the efficacy and safety of imlifidase in highly sensitized paediatric patients, 1-17 years old, with end stage renal disease (ESRD).
The main questions it aims to answer are:
- Does imlifidase treatment result in crossmatch conversion that enables transplantation?
- How is the function of the transplanted kidney?
The participants will be hospitalised in accordance with the normal routines for transplanted patients. The patients will receive medication to prevent rejection of the donor kidney, and because such treatment make the body more vulnerable medications to prevent infections.
详细描述
After being informed about the study and potential risks, all patients giving written informed consent will undergo pre-screening to determine eligibility for study entry.
The trial will include highly sensitised ESRD paediatric patients (1-17 years). The patients have previously undergone desensitization unsuccessfully or have an anti-HLA antibody status deemed too difficult to make a successful desensitization using other experimental methods.
A screening visit will take place when an organ offer has been placed for a final check of the patients' eligibility for study participation.
All patients included in the trial will be desensitized with imlifidase to convert the positive XM to negative and then transplanted with either a kidney from a deceased donor (DD) or a living donor (LD).
Patients will be hospitalised in accordance with the normal routines for transplanted patients at each clinic.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed Informed Consent obtained from patient/parent/legal guardian/independent witness (depending on patient's age) before any trial-related procedures
- •Highly sensitised patient with panel reactive antibodies (PRA) ≥80%
- •Male or female patient between the age of 1 to 17 years (up to the day before the 18th birthday) at the time of screening
- •Patient with end-stage renal disease (ESRD) and waiting for a renal transplant from a living or deceased donor
- •Patient must be transplantable (including size mismatch) at the time of obtaining informed consent for trial participation
- •Patients who have previously undergone desensitisation unsuccessfully with plasmapheresis/IVIg/anti-CD20 or have an anti-HLA antibody status deemed too difficult to make a successful desensitisation (judgement based on physicians' previous experience with similar patients)
- •Positive crossmatch (XM) test determined by flow cytometry crossmatch (FCXM) and/or complement-dependent cytotoxicity crossmatch (CDCXM) tests against the donor. For the DD patients, if physical XM tests are not practically possible due to lack of time, patients may be included on a virtual crossmatch (vXM) predictive of a positive XM test.
- •Willingness and ability to comply with the protocol as judged by the investigator
排除标准
- •Previous treatment with imlifidase
- •IVIg treatment within 28 days prior to imlifidase treatment
- •Desensitisation treatment(s) within 1 month prior to the current transplantation
- •Hypersensitivity to the active substance (imlifidase) or to any of the excipients and to other immunosuppressive drugs specified in the protocol
- •Ongoing serious infections
- •Present, or history of, thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP
- •At the time of transplantation: severe other condition requiring treatment and close monitoring e.g. cardiac failure ≥ grade 4 (New York Heart Association), unstable coronary disease, active peripheral vascular disease, proven hypercoagulable conditions/events or oxygen dependent respiratory disease
- •Malignancy within 3 years prior to transplantation
- •ABO blood group incompatible transplantations (A2 and A2B kidneys will not be accepted for B recipients)
- •Any other reason that, in the view of the investigator, precludes transplantation
- •Breast feeding or pregnancy, if applicable
- •Woman of fertile age and sexually active without adequate contraceptive measures to avoid pregnancy during the interventional trial period (i.e. up to 6 months after transplantation)
- •Suspicion of Covid-19 infection or positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test
- •Positive serology for human immunodeficiency virus (HIV)
- •Clinical signs of hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV), or Epstein Barr virus (EBV) infection
- •Donor with positive serology for HIV, HBV, HCV or CMV to a patient with negative serology (mismatch serology). Mismatch serology for EBV in accordance with center specific standard procedures for transplantation of EBV negative recipients and at investigator's discretion.
- •Clinically relevant active infection(s) as judged by the investigator
- •Tuberculosis or history of tuberculosis
- •Use of other investigational agents within 5 terminal elimination half-lives prior to the transplantation
- •Contemporaneous participation in medical device studies
- •Known mental incapacity or language barriers precluding patients'/parents'/legal guardians' adequate understanding of the informed consent information and the trial activities
- •Inability by the judgement of the investigator to participate in the trial for any other reason
研究组 & 干预措施
Imlifidase
Imlifidase is administered intravenously as one infusion of 0.25 mg/kg over 15 minutes within 24 hours prior to transplantation.
干预措施: Imlifidase (Drug)
结局指标
主要结局
Proportion of patients with conversion of a positive crossmatch test to negative within 24 hours after start of imlifidase treatment
时间窗: From start of imlifidase administration to 24 hours
Immunoglobulins (IgG) including donor specific antibodies (DSAs) are rapidly and efficiently cleaved by imlifidase. A conversion of a positive to a negative XM will enable transplantation.
次要结局
- Renal function up to 5 years after transplantation as assessed by estimated glomerular filtration rate (eGFR)(From pre-dose imlifidase up to 5 years)
- Renal function up to 5 years after transplantation as assessed by serum/plasma cystatin C levels(From pre-dose imlifidase up to 5 years)
- Proportion of patients with biopsy- and serology (DSA)-confirmed AMR up to 5 years after transplantation(From transplantation up to 5 years)
- Proportion of patients with biopsy confirmed cell-mediated rejection (CMR) up to 5 years after transplantation(From transplantation up to 5 years)
- Renal function up to 5 years after transplantation as assessed by proteinuria(From pre-dose imlifidase up to 5 years)
- DSA levels up to 5 years after transplantation(From pre-dose imlifidase up to 5 years)
- Graft survival (death censored) up to 5 year after transplantation(From 6 months up to 5 years)
- Graft failure-free survival up to 5 years after transplantation(From 6 months up to 5 years)
- Patient survival up to 5 years after transplantation(From 6 months up to 5 years)
- Proportion of patients with dialysis dependency up to 5 years after transplantation(From 6 months up to 5 years)
- Imlifidase Pharmacokinetics (AUC)(From pre-dose imlifidase up to Day 15)
- Renal function up to 5 years after transplantation as assessed by serum/plasma creatinine levels(From pre-dose imlifidase up to 5 years)
- Frequency of delayed graft function (DGF)(From transplantation up 7 days after transplantation)
- Length of DGF(From transplantation up 7 days after transplantation)
- Imlifidase Pharmacokinetics (Cmax)(From pre-dose imlifidase up to Day 15)
- Imlifidase Pharmacokinetics (t1/2)(From pre-dose imlifidase up to Day 15)
- Imlifidase Pharmacokinetics (CL)(From pre-dose imlifidase up to Day 15)
- Immunogenicity profile of imlifidase up to 5 years after imlifidase treatment(From pre-dose imlifidase up to 5 years)
- Imlifidase Pharmacokinetics (tmax)(From pre-dose imlifidase up to Day 15)
- Imlifidase Pharmacodynamic (PD) profile up to 9 days after imlifidase treatment(From pre-dose imlifidase up to Day 10)
- Imlifidase Pharmacokinetics (Vz)(From pre-dose imlifidase up to Day 15)