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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01794663
Other study ID # OPN305-102
Secondary ID 2012-001455-39
Status Completed
Phase Phase 2
First received February 13, 2013
Last updated February 15, 2017
Start date October 2012
Est. completion date June 30, 2016

Study information

Verified date February 2017
Source Opsona Therapeutics Ltd.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 252
Est. completion date June 30, 2016
Est. primary completion date June 30, 2016
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Exclusion Criteria

EXCLUSION CRITERIA FOR TRANSPLANT RECIPIENTS:

- Use of an investigational drug in the 30 days before Study Day 1

- Participation in any other research

- Known hypersensitivity to human monoclonal antibodies or any of the study-drug excipients

- Previous hypersensitivity to basiliximab or anti-thymocyte globulin (ATG)

- History or known HIV, HBV, or HCV-positive

- History of malignancy within the last five years, except excised squamous or basal cell carcinoma of the skin or cervical intraepithelial neoplasia

- Scheduled to undergo multi-organ transplantation

- Planned dual kidney transplantation

- Presence of clinically significant infections requiring continued therapy

- Active tuberculosis

- Existence of any surgical or medical condition, other than the current transplantation which, in the opinion of the investigator, might significantly alter the distribution, metabolism or excretion of study medication

- Presence of uncontrolled diabetes mellitus.

- Current drug and/or alcohol abuse

- History or presence of a medical condition or disease that in the investigator's assessment would place the patient at an unacceptable risk for study participation

- Lactating or pregnant woman

- Patient institutionalized by administrative or court order

EXCLUSION CRITERIA FOR ALL DONOR KIDNEYS

- DCD or SCD donor kidney

- Terminal creatinine >3mg/dL

- Donor who is known to have received an investigational drug for I-R injury or graft rejection (immunosuppressant) in the 48h before organ recovery

- Participation in any other research (drug or non-drug)

- Kidney donor <5 years of age or <20kg body weight

- Living donor allograft

- HLA or ABO incompatible kidney as defined by a negative cytotoxic crossmatch

- Donor institutionalized by administrative or court order

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
OPN-305
Intravenous infusion for 1 hour at start of transplant procedure
Placebo
Intravenous infusion for 1 hour at start of transplant procedure

Locations

Country Name City State
Austria Research Site Linz
Belgium Research Site Brussels
Belgium Research Site Gent
Belgium Research Site Leuven
Belgium Research Site Liege
Czech Republic Research Site Praha
France Research Site Bordeaux
France Research Site Paris
France Research Site Toulouse
Germany Research Site Berlin
Germany Research Site Berlin
Germany Research Site Bochum
Germany Research Site Bonn
Germany Research Site Erlangen
Germany Research Site Heidelberg
Germany Research Site Koln
Germany Research Site Mannheim
Germany Research Site Munster
Germany Research Site Tubingen
Netherlands Research Site Groningen
Netherlands Research Site Leiden
Netherlands Research Site Nijmegen
Netherlands Research Site Rotterdam
Poland Research Site Bydgoszcz
Poland Research Site Lodz
Poland Research Site Szczecin
Poland Research Site Warsaw
Poland Research Site Warszawa
Spain Research Site Barcelona
Spain Research Site Barcelona
Spain Research Site Barcelona
Spain Research Site Madrid
Spain Research Site Santander
Switzerland Research Site Zurich
United Kingdom Research Site London
United Kingdom Research Site Newcastle upon Tyne
United States Research Site Bronx New York
United States Research Site Charleston South Carolina
United States Research Site Chicago Illinois
United States Research Site Dallas Texas
United States Research Site Fort Worth Texas
United States Research Site Harrisburg Pennsylvania
United States Research Site Livingston New Jersey
United States Research Site Los Angeles California
United States Research Site New Orleans Louisiana
United States Research Site New Orleans Louisiana
United States Research Site New York New York
United States Research Site Richmond Virginia
United States Research Site Tampa Florida
United States Research Site Washington District of Columbia

Sponsors (1)

Lead Sponsor Collaborator
Opsona Therapeutics Ltd.

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Czech Republic,  France,  Germany,  Netherlands,  Poland,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Measure of Early Graft Function EGF 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 First 7 days following renal transplantation
Secondary Creatinine at 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 7 and 14 days and at 1, 3 and 6 months
Secondary Cystatin C at 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 7 and 14 days and at 1, 3 and 6 months
Secondary Symmetrical dimethylarginine at 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 7 and 14 days and at 1, 3 and 6 months
Secondary Incidence of slow graft function Slow graft function to be assessed over first 5 days post-transplant 5 days post-transplant
Secondary Serum creatinine over time Measure of Serum creatinine over time over the duration of follow-up
Secondary Composite endpoint 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
6 months
Secondary Time to biopsy-proven kidney allograft rejection Time to biopsy-proven kidney allograft rejection 6 months
Secondary Time to first dialysis or functional delayed graft function and delayed graft function duration 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
30 days
Secondary Blood and urine biomarkers for acute kidney injury (AKI) Serum NGAL, urinary NGAL, a-GST, p-GST, KIM-1 and IL-18 days 2, 7, 14, 28, 90 and 180
Secondary Duration of initial hospitalization Duration of initial hospitalization 6 months
Secondary Duration of subsequent readmissions Duration of subsequent readmissions 6 months
Secondary Reason for subsequent readmissions Reason for subsequent readmissions 6 months
Secondary Number of Adverse events (AEs) Number of Adverse events (AEs) 6 months
Secondary Nature of Adverse events (AEs) Nature of Adverse events (AEs) 6 months
Secondary Incidence of infections Incidence of infections by category and organism 6 months
Secondary Rate of primary non-function (permanent lack of function of the allograft) 6 months
Secondary Number of dialysis sessions between 0 and 30 days post-transplantation Number of dialysis sessions between 0 and 30 days post-transplantation 30 days
See also
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Active, not recruiting NCT02568696 - Intra-graft Coagulation Events in Clinical Renal Transplantation and Delayed Graft Function
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Terminated NCT01878786 - A Pilot Study Comparing the Safety and Efficacy of Everolimus With Other Medicines in Recipients of ECD/DCD Kidneys Phase 2/Phase 3
Active, not recruiting NCT01395719 - Context - Remote Ischemic Conditioning in Renal Transplantation - Effect on Immediate and Extended Kidney Graft Function N/A