Clinical Trial: Placebo-Controlled Study to Evaluate the Safety and Efficacy of OPN-305 in Preventing Delayed Renal Graft Function
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: A Three-Part, Multi-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel-Group, Sequential Adaptive, Phase II Study to Evaluate the Safety, Tolerability and Efficacy of OPN-305, a Humanised
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,
Detailed Summary:
Sponsor: Opsona Therapeutics Ltd.
Current Primary Outcome: Measure of Early Graft Function EGF [ Time Frame: First 7 days following renal transplantation ]
Original Primary Outcome: Incidence of Delayed Graft Function (dDGF) [ Time Frame: First 7 days following renal transplantation ]
Current Secondary Outcome:
- Creatinine at 7 and 14 days and at 1, 3 and 6 months [ Time Frame: 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
- Cystatin C at 7 and 14 days and at 1, 3 and 6 months [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 5 days post-transplant ]Slow graft function to be assessed over first 5 days post-transplant
- Serum creatinine over time [ Time Frame: over the duration of follow-up ]Measure of Serum creatinine over time
- Composite endpoint [ Time Frame: 6 months ]
Components of the composite endpoint are:
- Incidence of biopsy-proven kidney allograft rejection (biopsies will be done on a for-cause basis only)
- Graft loss
- Reports of patient death(s)
- Patients lost to follow-up
- Time to biopsy-proven kidney allograft rejection [ Time Frame: 6 months ]Time to biopsy-proven kidney allograft rejection
- Time to first dialysis or functional delayed graft function and delayed graft function duration [ Time Frame: 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) [ Time Frame: days 2, 7, 14, 28, 90 and 180 ]Serum NGAL, urinary NGAL, α-GST, π-GST, KIM-1 and IL-18
- Duration of initial hospitalization [ Time Frame: 6 months ]Duration of initial hospitalization
- Duration of subsequent readmissions [ Time Frame: 6 months ]Duration of subsequent readmissions
- Reason for subsequent readmissions [ Time Frame: 6 months ]Reason for subsequent readmissions
- Number of Adverse events (AEs) [ Time Frame: 6 months ]Number of Adverse events (AEs)
- Nature of Adverse events (AEs) [ Time Frame: 6 months ]Nature of Adverse events (AEs)
- Incidence of infections [ Time Frame: 6 months ]Incidence of infections by category and organism
- Rate of primary non-function (permanent lack of function of the allograft) [ Time Frame: 6 months ]
- Number of dialysis sessions between 0 and 30 days post-transplantation [ Time Frame: 30 days ]Number of dialysis sessions between 0 and 30 days post-transplantation
Original Secondary Outcome:
- Functional Delayed Graft Function (fDGF) [ Time Frame: 7 days following transplantation ]Failure to reduce serum creatinine by at least 10% per day during 3 successive days in the first 7 days following transplant surgery
- Serum creatinine at day 7 and 6 months [ Time Frame: day 7 and 6 months ]Measure of creatinine at day 7 and 6 months
- Iohexol clearance at day 7 and 6 months [ Time Frame: day 7 and 6 months ]Measure of iohexol clearance at day 7 and 6 months
- Composite endpoint [ Time Frame: 6 months ]
Components of the composite endpoint are:
- Incidence of biopsy-proven kidney allograft rejection (biopsies will be done on a for-cause basis only)
- Graft loss
- Incidence of patient death(s)
- Patients lost to follow-up
- Time to biopsy-proven kidney allograft rejection [ Time Frame: 6 months ]Time to biopsy-proven kidney allograft rejection
- Time to first dialysis and DGF duration [ Time Frame: 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) [ Time Frame: days 2, 7, 14, 28, 90 and 180 ]Serum NGAL and Cystatin C, urinary NGAL, α-GST, π-GST, KIM and IL-18
- Duration of initial hospitalization [ Time Frame: 6 months ]Duration of initial hospitalization
- Number of subsequent readmissions [ Time Frame: 6 months ]Number of subsequent readmissions
- Duration of subsequent readmissions [ Time Frame: 6 months ]Duration of subsequent readmissions
- Reason for subsequent readmissions [ Time Frame: 6 months ]Reason for subsequent readmissions
- Number of Adverse events (AEs) [ Time Frame: 6 months ]Number of Adverse events (AEs)
- Nature of Adverse events (AEs) [ Time Frame: 6 months ]Nature of Adverse events (AEs)
- Incidence of infections [ Time Frame: 6 months ]Incidence of infections by category and organism
- Rate of primary non-function (permanent lack of function of the allograft) [ Time Frame: 6 months ]
- Incidence of the initiation of dialysis between 7 and 30 days post-transplantation [ Time Frame: 30 days ]Incidence of the initiation of dialysis between 7 and 30 days post-transplantation
Information By: Opsona Therapeutics Ltd.
Dates:
Date Received: February 13, 2013
Date Started: October 2012
Date Completion:
Last Updated: February 15, 2017
Last Verified: February 2017
