Delayed Graft Function
Conditions
Keywords
Early kidney graft dysfunction, renal transplantation
Brief summary
When a patient receives a kidney transplant particularly if the kidney is from an older donor or one who has had the kidney removed after their heart has stopped, there is a risk that the newly transplanted kidney may not function immediately. If the delay in function means that dialysis is needed in the first 7 days after the transplantation then this is known as delayed graft function or dDGF. Also delayed graft function that does not require dialysis but is present because the serum creatinine does not fall sufficiently is known as functional delayed graft function or fDGF. This problem is often due to an excessive inflammatory reaction to not having had a blood supply between the time of donation and transplant. OPN-305 is a monoclonal antibody that blocks Toll-like Receptor 2 which is thought to be partly responsible for increasing the risk of this inflammation. It is hoped that the effects of the inflammation will be reduced and therefore prevent dDGF and fDGF from occurring. The purpose of the study is to explore how effective OPN-305 is in preventing dDGF and fDGF as well as improving other measures of kidney function and the overall safety of the antibody. In the first part of the study, each patient received an Infusion of one of three possible doses of OPN-305 or a placebo and in the second part the most suitable dose of OPN-305 and a placebo would be used. The purpose of this second part of the study is to find out if a dose of OPN-305 which has already been tested in an earlier part of this study can prevent kidney graft dysfunction. For the purposes of this study, kidney function will be assessed using the composite of delayed graft function (dDGF) because dialysis is necessary in the first 7 days and functional delayed graft function that does not require dialysis but is present because the serum creatinine, a key measure of renal function, does not fall sufficiently (fDGF) in the first 7 days post-transplant. Protocol OPN305-103 follows out to 12 months post-transplant the clinical status and graft function of patients who have completed the 6-month post-transplant period under Part A or Part B of OPN305-102.
Interventions
DRUGOPN-305
Intravenous infusion for 1 hour at start of transplant procedure
DRUGPlacebo
Intravenous infusion for 1 hour at start of transplant procedure
Sponsors
Opsona Therapeutics Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
INCLUSION CRITERIA FOR TRANSPLANT RECIPIENTS * First or second renal transplant recipient - for second renal transplantations; * The second transplant should NOT be due to rejection * Panel Reactive Antibody (PRA) should be \<10% * Minimum 3 months since the loss of the first transplanted kidney * Dialysis-dependent at the time of transplantation as documented by: * Requirement for at least 2 dialysis sessions/week in the 56 days before transplantation INCLUSION CRITERIA FOR DONOR KIDNEY: * The donor kidney must be considered compatible according to local transplant guidelines * An ECD donor defined as: o Extended Criteria Donor defined as: * Donor ≥60 years of age * Donor 50-59 years of age with two of three of the following criteria present: * Death due to cerebrovascular accident * Pre-existing history of systemic hypertension * Terminal creatinine \> 1.5mg/dL (132.6 µmol/L) * Kidney allograft maintained in cold storage with or without machine perfusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measure of Early Graft Function EGF | First 7 days following renal transplantation | Initiation of dialysis in the first 7 days following renal transplantation and failure of serum creatinine to decrease by at least 10% daily on 3 successive days during the first week post transplantation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cystatin C at 7 and 14 days and at 1, 3 and 6 months | 7 and 14 days and at 1, 3 and 6 months | Measure of Cystatin C at 7 and 14 days and at 1, 3 and 6 months |
| Symmetrical dimethylarginine at 7 and 14 days and at 1, 3 and 6 months | 7 and 14 days and at 1, 3 and 6 months | Measure of symmetrical dimethylarginine at 7 and 14 days and at 1, 3 and 6 months |
| Incidence of slow graft function | 5 days post-transplant | Slow graft function to be assessed over first 5 days post-transplant |
| Serum creatinine over time | over the duration of follow-up | Measure of Serum creatinine over time |
| Composite endpoint | 6 months | Components of the composite endpoint are: 1. Incidence of biopsy-proven kidney allograft rejection (biopsies will be done on a for-cause basis only) 2. Graft loss 3. Reports of patient death(s) 4. Patients lost to follow-up |
| Time to biopsy-proven kidney allograft rejection | 6 months | Time to biopsy-proven kidney allograft rejection |
| Time to first dialysis or functional delayed graft function and delayed graft function duration | 30 days | Duration of DGF is defined as either: Time from transplantation to time of completion of final dialysis for DGF Time from transplantation to time when creatinine starts to fall by at least 10% without dialysis |
| Blood and urine biomarkers for acute kidney injury (AKI) | days 2, 7, 14, 28, 90 and 180 | Serum NGAL, urinary NGAL, α-GST, π-GST, KIM-1 and IL-18 |
| Creatinine at 7 and 14 days and at 1, 3 and 6 months | 7 and 14 days and at 1, 3 and 6 months | Measure of creatinine at 7 and 14 days and at 1, 3 and 6 months |
| Duration of subsequent readmissions | 6 months | Duration of subsequent readmissions |
| Reason for subsequent readmissions | 6 months | Reason for subsequent readmissions |
| Number of Adverse events (AEs) | 6 months | Number of Adverse events (AEs) |
| Nature of Adverse events (AEs) | 6 months | Nature of Adverse events (AEs) |
| Incidence of infections | 6 months | Incidence of infections by category and organism |
| Rate of primary non-function (permanent lack of function of the allograft) | 6 months | — |
| Number of dialysis sessions between 0 and 30 days post-transplantation | 30 days | Number of dialysis sessions between 0 and 30 days post-transplantation |
| Duration of initial hospitalization | 6 months | Duration of initial hospitalization |
Countries
Austria, Belgium, Czechia, France, Germany, Netherlands, Poland, Spain, Switzerland, United Kingdom, United States
Outcome results
None listed