Ignite Creation Date:
2025-12-24 @ 9:58 PM
Ignite Modification Date:
2026-02-26 @ 4:18 PM
Study NCT ID:
NCT02435732
Status:
UNKNOWN
Last Update Posted:
2020-10-22
First Post:
2015-04-21
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
CINRYZE as a Donor Pre-treatment Strategy in Kidney Recipients of KDPI>60%
Sponsor:
University of Wisconsin, Madison
Organization:
Study Overview
Official Title:
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%
Status:
UNKNOWN
Status Verified Date:
2020-10
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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%.
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%.
Detailed Description:
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.
Most of the donors with a Kidney Donor Profile Index (KDPI) \>60%, due to the fact that they are considered "extreme" donors, are not likely to be able to donate organs other than kidneys. They would certainly not be pancreas donors, and it is unlikely they would be lung donors. There is a small possibility that donors with a KDPI \>60% could be potential liver donors. In the event that a donor liver is available for transplant, we will obtain written consent from the liver recipient, as we will from the kidney recipient(s) before the donor is dosed with the CINRYZE/placebo.
For this study:
All donors will come from within our service area. All kidney and livers will be allocated to be transplanted at the UW.
Stage 1: Collection of initial safety data prior to expanding the study to a broad cohort of patients.
3 non-randomized donors: Step 1: Two kidney only donors treated with 200 units/kg C1INH and heparin at 20 units/kg/h IV maintenance until organ recovery Step 2: Two donors of both liver and kidneys, treated with 200 units/kg C1INH and heparin at 20 units/kg/h IV maintenance until organ recovery The 8 kidneys and 2 livers in Stage 1 will be allocated to be transplanted only at UW.
Stage 2: PK Study, Safety and Outcome Data
36 donors will be randomized into 3 groups:
Group 1: Control group: standard donor management + vehicle treatment (n=12) Group 2: Standard donor management + C1INH at a dose of 200 U/Kg IV single dose (n=12) Group 3: Standard donor management + C1INH at a dose of 200 units/kg IV single dose and heparin at 20 units/kg/h IV maintenance until organ recovery (n=12)
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.
Most of the donors with a Kidney Donor Profile Index (KDPI) \>60%, due to the fact that they are considered "extreme" donors, are not likely to be able to donate organs other than kidneys. They would certainly not be pancreas donors, and it is unlikely they would be lung donors. There is a small possibility that donors with a KDPI \>60% could be potential liver donors. In the event that a donor liver is available for transplant, we will obtain written consent from the liver recipient, as we will from the kidney recipient(s) before the donor is dosed with the CINRYZE/placebo.
For this study:
All donors will come from within our service area. All kidney and livers will be allocated to be transplanted at the UW.
Stage 1: Collection of initial safety data prior to expanding the study to a broad cohort of patients.
3 non-randomized donors: Step 1: Two kidney only donors treated with 200 units/kg C1INH and heparin at 20 units/kg/h IV maintenance until organ recovery Step 2: Two donors of both liver and kidneys, treated with 200 units/kg C1INH and heparin at 20 units/kg/h IV maintenance until organ recovery The 8 kidneys and 2 livers in Stage 1 will be allocated to be transplanted only at UW.
Stage 2: PK Study, Safety and Outcome Data
36 donors will be randomized into 3 groups:
Group 1: Control group: standard donor management + vehicle treatment (n=12) Group 2: Standard donor management + C1INH at a dose of 200 U/Kg IV single dose (n=12) Group 3: Standard donor management + C1INH at a dose of 200 units/kg IV single dose and heparin at 20 units/kg/h IV maintenance until organ recovery (n=12)
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: