Placebo-Controlled Study to Evaluate the Safety and Efficacy of OPN-305 in Preventing Delayed Renal Graft Function

Phase 2

Completed

• Conditions: Delayed Graft Function
• Interventions: Drug: OPN-305; Drug: Placebo

• Registration Number: NCT01794663
• Lead Sponsor: Opsona Therapeutics Ltd.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-10
• Study First Submitted: 2013-02-13
• Study First Submitted QC: 2013-02-15
• Study First Posted: 2013-02-20
• Primary Completion: 2016-06-30
• Study Completion: 2016-06-30
• Status Verified: 2017-02
• Disposition First Submitted: 2017-02-10
• Disposition First Submitted QC: 2017-02-10
• Disposition First Posted: 2017-02-13
• Last Update Submitted: 2017-02-15
• Last Update Posted: 2017-02-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 252

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
OPN-305	OPN-305	-
Matching placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Number of Adverse events (AEs)	6 months	Number of Adverse events (AEs)
Reason for subsequent readmissions	6 months	Reason for subsequent readmissions
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
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
Duration of initial hospitalization	6 months	Duration of initial hospitalization
Duration of subsequent readmissions	6 months	Duration of subsequent readmissions
Nature of Adverse events (AEs)	6 months	Nature of Adverse events (AEs)
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
Incidence of infections	6 months	Incidence of infections by category and organism

Trial Locations

Locations (1)

Research Site; 🇬🇧 Newcastle upon Tyne, United Kingdom