Ischemia-reperfusion Injury, Kidney Transplant; Complications
Conditions
Keywords
Ex-vivo kidney allograft treatment, kidney transplantation, Transplant outcome, Ischemia-reperfusion Injury
Brief summary
Randomized (1:1), placebo controlled, double blind efficacy trial. 200 patients will be followed up for 12 months post transplantation. The primary endpoint will be Delayed Graft Function (DGF) defined as the requirement for dialysis within 7 days post transplantation.
Detailed description
The present trial aims to evaluate if iCM012 solution 2 mg/mL can improve short and mid-term allograft function of controlled donation after circulatory death (DCD) kidneys at high risk for Ischemia Reperfusion Injury (IRI) -induced graft dysfunction as assessed by primarily DGF and secondary as estimated glomerular filtration rates (eGFR). The trial will also generate additional efficacy, safety, and exploratory data.
Interventions
DRUGiCM012 solution 2 mg/mL
200 mL IMP solution is administered ex vivo by gravity as single infusion through the renal artery/-ies over a period of 5-10 minutes.
DRUGPlacebo
200 mL IMP solution is administered ex vivo by gravity as single infusion through the renal artery/-ies over a period of 5-10 minutes.
Sponsors
iCoat Medical AB
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
To be eligible for use in this trial, an allograft must meet the following criterion: 1. Controlled DCD donors Maastricht category III from 55 to 75 years of age. To be eligible to participate in this trial, a patient must meet all the following criteria: 2. Available, personally signed and dated Informed Consent Form. 3. Male or female chronic kidney disease (CKD) ≥ 18 years of age, on dialysis > 12 months, awaiting their first kidney transplantation. 4. AB0-compatible, negative pre-transplantation Complement Dependent Cytotoxicity (CDC) and/or flow cytometric class I and II crossmatch, or negative virtual class I and II crossmatch, and no pre-existing donor specific antibodies (Mean Fluorescent Intensity under center specific cut-off for negative value). 5. Completed vaccination program according to local standard practice or as deemed relevant by the investigator.
Exclusion criteria
An allograft that meets any of the following criteria will be excluded from use in this trial: 1. Surgically induced injuries or anatomical vascular variations compromising ex vivo treatment and/or transplantation outcome, as judged by the investigator. 2. DCDs with persistent and significant deterioration of kidney function (30% decrease in eGFR from baseline) and/or on dialysis within two (2) weeks prior to organ procurement and/or anuria > 12 hours before surgery. 3. Extracorporeal membrane oxygenation treatment of the donor A patient who meets any of the following criteria will be excluded from participation in this trial: 4. If not tolerating/eligible for thymoglobulin induction and tacrolimus or Cyclosporine A (CyA)-based maintenance immunosuppressants. 5. Previously undergone any organ and/or cell transplantations. 6. Positive CDC and or flow cytometric class I and/or II crossmatch, and/or positive virtual crossmatch. 7. Highly sensitized patients defined by Panel Reactive Antibody (PRA) level equal or higher than 98%. 8. AB0-incompatible deceased donor kidney transplantation. 9. Pregnant or breast-feeding woman. 10. Woman of child-bearing potential, not using an adequate contraceptive method. 11. Prior participation in a clinical trial with (approved or non-approved) IMPs within 1 month prior to screening for this trial. 12. Prior malignancy diagnosis ≤ 5 years, except for adequately treated basal cell, or squamous cell skin cancer, and carcinoma in situ, or judged as irrelevant by the investigator. 13. Positive result for serum human immunodeficiency virus (HIV), active hepatitis B or C infection in pre-transplantation evaluation. 14. History of severe drug allergy or hypersensitivity, or known hypersensitivity, or intolerance to any of the IMPs or its/their excipients. 15. Concomitant severe conditions requiring treatment and close monitoring, as judged by the investigator. 16. 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. 17. Unlikely to comply with trial procedures, restrictions, and requirements (e.g., caused by substance abuse, concurrent medical condition, etc.), as judged by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Delayed Graft Function (DGF) | First 7 postoperative days. | DGF is defined as the need for dialysis within the first 7 postoperative days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Primary non-function | 12 months post transplantation | Primary non-function (PNF) describes the condition in which the kidney never functions adequately after transplantation, and the patient continues to need dialysis despite the transplantation. The diagnosis of PNF generally does not become established before 2 to 3 months after transplantation. Assessed up to 12 months after transplantation |
| Number of Participants with prolonged DGF | 14 days post transplantation | Number of Participants with prolonged DGF (defined as requirement for dialysis more than 14 days post transplantation) |
| Number of Participants with functional DGF | First 7 days post-transplantation | Number of Participants with functional DGF (defined as no serum creatinine decrease by at least 10% daily on 3 consecutive days within the first 7 days post-transplantation) |
| Duration of dialysis sessions (hours) | First 30- and 90-days post-transplantation | Duration of dialysis sessions within the first 30- and 90-days post-transplantation. Measured in hours. |
| eGFR over 12 months post transplantation | 12 months post transplantation | Estimated Glomerular Filtration Rate using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation with four (4) variables (serum creatinine, age, gender, and ethnicity) |
| Changes in Quality of Life | 12 months post transplantation | Quality of Life EuroQol - five dimensions - three levels (EQ-5D-3L) Assessed through standardized questionnaires, results combined to single summary index (0-1: 0 is death, 1 is perfect health). |
| Incidence of de novo Human Leukocyte Antigen (HLA) antibodies within 12 months | 12 months post transplantation | Incidence of de novo Human Leukocyte Antigen antibodies within 12 months |
| Incidence of biopsy-proven allograft rejection within 12 months | 12 months post transplantation | Incidence of biopsy-proven allograft rejection within 12 months |
| Tubular cell injury assessed by exploratory urinary biomarkers | 12 months post transplantation | Tubular cell injury assessed by exploratory urinary biomarkers; details not yet decided. |
| Number of dialysis sessions | First 30- and 90-days post-transplantation | Number of dialysis sessions within the first 30- and 90-days post-transplantation |
Contacts
Primary ContactIngegerd Dalfelt
Outcome results
None listed