Phase I FIH Phase I/IIa Randomized Placebocontrolled Doubleblind Trial Evaluating Safety and Tolerability of ExVivo Deceased Donor Kidney Allograft Treatment With TUM012 to Minimize Ischemic Reperfusion Injury After Kidney Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Adverse Events
研究概览
简要总结
A first-in-human single center, randomized, double-blind, placebo-controlled trial, with primary objective to evaluate safety and tolerability of ex-vivo kidney allograft treatment with TUM012 to reduce ischemia-reperfusion injury in de novo kidney transplant recipients.
详细描述
Graft ischemia and reperfusion related injury is still the leading cause of graft failure in Deceased Donor kidney transplantation. The aim of the trial is to evaluate the safety of ex-vivo treatment of kidney allografts from deceased-donors with TUM012 to diminish ischemia reperfusion related inflammation, and improve overall transplantat outcome.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Triple (Participant, Care Provider, Investigator)
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
- •Standard and extended criteria donor ≥18 years of age, suitable for clinical transplantation and preserved by cold storage.
- •Available, personally signed and dated Informed Consent Form (ICF)
- •Male or female Chronic Kidney Disease (CKD) patient ≥18 years of age, with Glomerular Filtration Rate (GFR) ≤15 mL/min, awaiting their first kidney transplantation
- •ABO-compatible, negative pre-transplant CDC class I and II crossmatch with no Donor Specific Antibodies (DSA), defined as ≤1 000 Mean Fluorescent Intensity (MFI).
- •Patient is suitable for surgery, as judged by the investigator
- •Completed vaccination program for pneumococcal disease, varicella zoster, measles, and SARS-CoV-2 virus
排除标准
- •Surgically induced injuries compromising ex-vivo treatment and/or transplant outcome, as judged by the transplantation surgeon
- •Previously undergone any organ and/or cell transplantations
- •Patients with positive CDC class I and/or II crossmatch, or negative CDC class I and II crossmatch with pre-existing DSA > 1,000 MFI
- •ABO-incompatible DD KT
- •Pregnant or breast-feeding woman
- •Woman of child-bearing potential, unwilling to use an adequate contraceptive method
- •Prior participation in clinical trial with (approved or non-approved) IMP within one month prior to screening for this trial.
- •Prior malignancy diagnosis ≤5 years, except for adequately treated basal cell, or squamous cell skin cancer, and cervical carcinoma in situ
- •Positive result for serum Human Immunodeficiency Virus (HIV), active hepatitis B-, or C-infection in pre-transplant evaluation
- •Clinical signs of ongoing infectious disease, defined as C-Reactive Protein (CRP) >10, unless stable since >4 weeks (<50% increase)
- •Concomitant severe conditions requiring treatment and close monitoring, e.g., cardiac failure >grade 3 New York Heart Association (NYHA), unstable coronary disease, or oxygen dependent Chronic Obstructive Pulmonary Disease (COPD)
- •History of any other clinically significant disease or disorder which, in the opinion of the investigator, may either put the patient at increased risk because of participation in the trial, or influence the results or the patient's ability to participate in the trial
- •Patient unlikely to comply with trial procedures, restrictions, and requirements (e.g., caused by substance abuse, concurrent medical condition, etc.), as judged by investigator
研究组 & 干预措施
Placebo
Ex-vivo infusion
干预措施: Placebo (Drug)
TUM012
Ex-vivo infusion
干预措施: TUM012 (Drug)
结局指标
主要结局
Adverse Events
时间窗: Three months from randomization
Number of patients with confirmed IMP-related events
Systolic/diastolic BP (Standard of Care Safety)
时间窗: Three months from randomization
Assessment: "normal", "abnormal, not clinically significant", or "abnormal clinically significant"
Laboratory Analyses (Standard of Care Safety)
时间窗: Three months from randomization
Assessment: "normal", "abnormal, not clinically significant", or "abnormal, clinically significant", will as appropriate be reported as Adverse Events.
Peripheral blood oxygenation (Standard of Care Safety)
时间窗: Three months from randomization
Assessment: "normal", "abnormal, not clinically significant", or "abnormal clinically significant"
12-lead Electro-Cardiogram (Standard of Care Safety)
时间窗: Three months from randomization
Assessment: "normal", "abnormal, not clinically significant", or "abnormal, clinically significant"
Pulse Rate (Standard of Care Safety)
时间窗: Three months from randomization
Assessment: "normal", "abnormal, not clinically significant", or "abnormal clinically significant"
Body temperature (Standard of Care Safety)
时间窗: Three months from randomization
Assessment: "normal", "abnormal, not clinically significant", or "abnormal clinically significant"
次要结局
- Exploratory Efficacy: Proteomics(Three months from randomization)
- Exploratory Efficacy: Markers of IR injury and thromboinflammation plasma level(Three months from randomization)
- Exploratory histological evaluation of kidney graft(Three months from randomization)
- Exploratory kidney graft function(Three months from randomization)
- Exploratory Efficacy: Cytokine release plasma level(Three months from randomization)
- Exploratory Efficacy: Immune cell graft recruitment plasma level(Three months from randomization)
- Exploratory Efficacy: Pharmacokinetics plasma concentration(Three months from randomization)