An Open-label, Controlled, Randomized Phase 3 Trial Evaluating 12-month Kidney Function in Highly Sensitized (cPRA ≥99.9%) Kidney Tx Patients With Positive XM Against a Deceased Donor, Comparing Desensitization Using Imlifidase With SoC
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 25
- 主要终点
- Mean estimated glomerular filtration rate (eGFR) at 12 months
研究概览
简要总结
An open-label, controlled, randomized Phase 3 trial evaluating 12-month kidney function in highly sensitized (cPRA ≥99.9%) kidney transplant patients with positive crossmatch against a deceased donor, comparing desensitization using imlifidase with standard of care
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.
Once an organ offer is received, a virtual crossmatch (vXM) is performed. If the crossmatch is considered predictive of a positive flow cytometry crossmatch (FCXM), the patient will be evaluated if eligible to receive the desensitization currently in use at the study site. Subsequently the patient will be randomized in a 1:1 ratio to the imlifidase or the control arm.
If the patient is randomized to the imlifidase arm, the organ will be accepted and shipped, and the patient will proceed to imlifidase treatment (generally within 24 h prior to transplantation) followed by transplantation. If the patient is randomized to the control arm, transplantation made possible by the local desensitization regimen will occur. If the institution-specific desensitization protocol is deemed not to be successful, the organ offer will be turned down, and the patient will remain active on the waiting list and remain in the trial, while the kidney will be allocated to another recipient through the kidney allocation system (KAS).
All transplanted patients will receive induction therapy and maintenance immunosuppression. All patients will be followed for 12 months.
Estimated glomerular filtration rate (eGFR) will be assessed 12 months after randomization as the primary endpoint reasonably likely to predict a clinical benefit in patient survival.
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
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（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
- •Male or female age 18-70 years at the time of screening
- •Chronic kidney disease (CKD) stage 5, highly sensitized as evaluated by standard selection criteria, and active on the OPTN waiting list for a DD kidney transplant
- •Original calculated panel reactive antibody (cPRA) ≥99.9%
- •Virtual crossmatch (vXM), predictive of a positive crossmatch to an available deceased donor (DD)
- •Willingness and ability to comply with the protocol
- •Willingness to participate in the planned 4-year extension trial
排除标准
- •High dose IVIg (2 g/kg) treatment within 28 days prior to imlifidase treatment
- •Previous treatment with imlifidase
- •Breast feeding or pregnancy
- •Women of child-bearing potential not willing or able to practice FDA-approved forms of contraception, or abstinence. Two medically acceptable methods of highly effective contraception must be used for the duration of the study (e.g. oral, transdermal, intravaginal, injectable or implantable contraceptive; intrauterine device; intrauterine hormone-releasing system; vasectomized partner; bilateral tubal occlusion; or double barrier method). For a woman to be considered postmenopausal this ascertainment must be made according to medical records and clinical history and may be aided by measurement of elevated postmenopausal serum gonadotropin levels (FSH).
- •ABO blood group incompatible transplantations (A2 or A2B kidneys will not be accepted for B recipients)
- •Positive serology for human immunodeficiency virus (HIV)
- •Clinical signs of hepatitis B virus (HBV) or hepatitis C virus (HCV) infections
- •Clinical signs of cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infections
- •Positive test for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (according to local hospital routines)
- •Active tuberculosis
- •Severe other conditions requiring treatment and close monitoring, e.g. cardiac failure ≥grade 4 (New York Heart Association), unstable coronary disease or oxygen dependent chronic obstructive pulmonary disease (COPD)
- •Any condition that in the view of the Investigator precludes transplantation
- •History of a proven hypercoagulable condition
- •Present or history of thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP
- •Intake of investigational drugs within 5 half-lives of the drug or 3 months, whichever is the longest
- •Contemporaneous participation in a medical device study
- •Known mental incapacity or language barriers precluding 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
Best available treatment
Institution-specific desensitization protocol (i.e. any combination of plasma exchange (PLEX), intravenous IVIg, anti-CD20 antibody, and eculizumab) where appropriate OR remain on wait list for a more compatible organ offer
干预措施: PLEX (Procedure)
Best available treatment
Institution-specific desensitization protocol (i.e. any combination of plasma exchange (PLEX), intravenous IVIg, anti-CD20 antibody, and eculizumab) where appropriate OR remain on wait list for a more compatible organ offer
干预措施: Anti-CD20 antibodies (Drug)
Best available treatment
Institution-specific desensitization protocol (i.e. any combination of plasma exchange (PLEX), intravenous IVIg, anti-CD20 antibody, and eculizumab) where appropriate OR remain on wait list for a more compatible organ offer
干预措施: IVIg (Drug)
Best available treatment
Institution-specific desensitization protocol (i.e. any combination of plasma exchange (PLEX), intravenous IVIg, anti-CD20 antibody, and eculizumab) where appropriate OR remain on wait list for a more compatible organ offer
干预措施: Remain on wait list (Other)
Imlifidase
Imlifidase, is provided as a freeze-dried powder for concentrate for solution for infusion, 11 mg per vial. After reconstitution with sterile water for injection, the concentrate contains 10 mg/mL imlifidase. Imlifidase is administered intravenously as one infusion of 0.25 mg/kg over 15 minutes generally 24 hours prior to transplantation. A second dose of 0.25 mg/kg may be given if the first imlifidase dose is considered not to have had sufficient effect.
干预措施: Imlifidase (Drug)
Best available treatment
Institution-specific desensitization protocol (i.e. any combination of plasma exchange (PLEX), intravenous IVIg, anti-CD20 antibody, and eculizumab) where appropriate OR remain on wait list for a more compatible organ offer
干预措施: Eculizumab (Drug)
结局指标
主要结局
Mean estimated glomerular filtration rate (eGFR) at 12 months
时间窗: 12 months after randomization
eGFR is a measure of kidney function and will be compared between treatment arms. eGFR will be calculated based on p-creatinine according to the modification of diet in renal disease (MDRD) equation. eGFR for a kidney with normal function is 90 mL/min/1.73m2. Kidney disease is characterised by a decreased eGFR value. For randomized patients who do not undergo transplantation, lose their graft or die before 12 months, eGFR will be set to zero, consistent with kidney failure.
次要结局
- Patient survival at 12 months(12 months after randomization)