A Phase I, Single Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Tolerability of C1 Inhibitor (CINRYZE) as a Donor Pre-treatment Strategy in Brain Dead Donors Who Meet a Kidney Donor Risk Index (KDRI) Above 60%
试验速览
- 阶段
- 1 期
- 入组人数
- 72
- 主要终点
- Lowest dose that will allow at least an 80% decrease in the activity of classic pathway and MBL pathway of complement in brain death donors with KDPI over 60%, with the purpose of reducing the incidence of delayed graft function.
研究概览
简要总结
Limiting brain death-induced organ injury through a systemic anti- inflammatory medical management should allow for improvement in the quality of transplanted organs, and as a result, clinical improvement in post-transplant outcomes represented by a decrease in the incidence of delayed graft function (DGF) after transplantation.
The specific aim is to evaluate the effect of C1INH (CINRYZE) as a donor pre-treatment strategy to decrease systemic inflammation and decrease the incidence of DGF in Expanded Criteria Donors (ECD), currently identified as donors with Kidney Donor Profile Index (KDPI) greater than or equal to 60%.
详细描述
This is a randomized, single-center double-blinded study.
Donor Pre-treatment Strategy:
The main objective is to identify the lowest dose that will allow an at least 80% decrease in the activity of classic pathway and Mannose-Binding Lectin (MBL) pathway of complement. The main objectives parallel observations in non-human primates in which animals receiving kidneys from donors in which activity of both classic and MBL pathways of complement were reduced by at least 50% with the use of C1 inhibitors displayed very mild or no delayed graft function after transplantation.
This trial has specifically been designed to evaluate the beneficial effect of C1INH in kidneys from deceased donors which have a high rate of delayed graft function. The selection of potential donors to be part of this study will be limited to the population of donors with a KDPI over 60%.
A total of 36 brain dead donors and 72 kidney recipients will be included in the study.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Use of an investigational drug in the 30 days before surgery.
- •Participation in any other research study (drug or non-drug) without prior approval from the Medical Monitor.
- •Known hypersensitivity to human monoclonal antibodies or any of the study drug excipients.
- •Previous hypersensitivity to basiliximab, Campath-1H or antithymocyte globulin (ATG)
- •History of or known HIV, HBV (surface antigen), or HCV positivity
- •History of malignancy within the last five years, except excised squamous or basal cell carcinoma of the skin, or cervical intraepithelial neoplasia.
- •Scheduled to undergo multi-organ transplantation.
- •Presence of clinically significant infections requiring continued therapy.
- •Positive screening for active tuberculosis.
- •Existence of any surgical or medical condition, other than the current transplantation which, in the opinion of the investigator, might significantly alter the distribution, metabolism or excretion of study medication.
- •History or presence of a medical condition or disease that in the investigator's assessment would place the patient at an unacceptable risk for study participation.
- •Lactating or pregnant woman.
- •Patient institutionalized by administrative or court order.
- •HLA or ABO incompatible kidney defined as a positive cytotoxic crossmatch, positive mean fluorescent intensity beyond the acceptable parameters by the institution, or flow crossmatch-based assay that is positive (for kidney recipients only)
- •Exclusion Criteria for Brain Dead Donor:
- •Donor who is known to have received an investigational drug for I-R injury or graft rejection (immunosuppressant) in the 48H prior to organ recovery
- •Participation in any other research study (drug or non-drug) without prior approval from the PI
- •Donor institutionalized by administrative or court order
- •Donors whose organs are allocated for transplantation to other transplant programs outside UW
- •Donors for which any of the intended organ recipients has not provided consent for the study
- •Donors that are donating other organs outside the scope of the study (i.e. heart, lungs, intestine) will be excluded.
研究组 & 干预措施
Control group
Standard donor management + vehicle treatment (n=9)- placebo saline solution
干预措施: Placebo saline solution (Drug)
CINRYZE 200 U/Kg IV
Intervention is CINRYZE 200 U/Kg IV single dose
干预措施: Placebo saline solution (Drug)
CINRYZE 200 U/Kg IV
Intervention is CINRYZE 200 U/Kg IV single dose
干预措施: CINRYZE (Drug)
200 units/kg IV CINRYZE with Heparin 20 U/kg/h IV
CINRYZE 200 units/kg IV single dose with Heparin at 20 units/kg/h IV maintenance until organ recovery
干预措施: Placebo saline solution (Drug)
200 units/kg IV CINRYZE with Heparin 20 U/kg/h IV
CINRYZE 200 units/kg IV single dose with Heparin at 20 units/kg/h IV maintenance until organ recovery
干预措施: Heparin (Drug)
200 units/kg IV CINRYZE with Heparin 20 U/kg/h IV
CINRYZE 200 units/kg IV single dose with Heparin at 20 units/kg/h IV maintenance until organ recovery
干预措施: CINRYZE (Drug)
结局指标
主要结局
Lowest dose that will allow at least an 80% decrease in the activity of classic pathway and MBL pathway of complement in brain death donors with KDPI over 60%, with the purpose of reducing the incidence of delayed graft function.
时间窗: over a 12 month period
Assessment of graft function
次要结局
- Rate of of DGF in kidney transplantation from ECD brain death donors(Within 6 hours of brain death)
- Donor Pharmacokinetics: plasma concentrations and Area under the Curve (AUC) for CINRYZE(At various timepoints within first 24 hours)
- Level of suppression of the classical and MBL pathways(Within 6 hours of brain death)
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability(Day of Transplant: first 24 hours, days 2-7, weeks 2,3,8, month 3, 6, 12)
- Levels of complement activation after brain death in donors treated with C1INH(Within 6 hours of brain death)