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

Primary Purpose

Delayed Graft Function

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
OPN-305
Placebo
Sponsored by
Opsona Therapeutics Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Delayed Graft Function focused on measuring Early kidney graft dysfunction, renal transplantation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

OPN-305

Matching placebo

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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
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
Incidence of slow graft function
Slow graft function to be assessed over first 5 days post-transplant
Serum creatinine over time
Measure of Serum creatinine over time
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
Time to biopsy-proven kidney allograft rejection
Time to biopsy-proven kidney allograft rejection
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
Blood and urine biomarkers for acute kidney injury (AKI)
Serum NGAL, urinary NGAL, α-GST, π-GST, KIM-1 and IL-18
Duration of initial hospitalization
Duration of initial hospitalization
Duration of subsequent readmissions
Duration of subsequent readmissions
Reason for subsequent readmissions
Reason for subsequent readmissions
Number of Adverse events (AEs)
Number of Adverse events (AEs)
Nature of Adverse events (AEs)
Nature of Adverse events (AEs)
Incidence of infections
Incidence of infections by category and organism
Rate of primary non-function (permanent lack of function of the allograft)
Number of dialysis sessions between 0 and 30 days post-transplantation
Number of dialysis sessions between 0 and 30 days post-transplantation

Full Information

First Posted
February 13, 2013
Last Updated
February 15, 2017
Sponsor
Opsona Therapeutics Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT01794663
Brief Title
Placebo-Controlled Study to Evaluate the Safety and Efficacy of OPN-305 in Preventing Delayed Renal Graft Function
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 Monoclonal Antibody That Blocks Toll-Like Receptor 2, in Renal Transplant Patients at High Risk of Delayed Graft Function
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
June 30, 2016 (Actual)
Study Completion Date
June 30, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Opsona Therapeutics Ltd.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Delayed Graft Function
Keywords
Early kidney graft dysfunction, renal transplantation

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
252 (Actual)

8. Arms, Groups, and Interventions

Arm Title
OPN-305
Arm Type
Experimental
Arm Title
Matching placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
OPN-305
Intervention Description
Intravenous infusion for 1 hour at start of transplant procedure
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Intravenous infusion for 1 hour at start of transplant procedure
Primary Outcome Measure Information:
Title
Measure of Early Graft Function EGF
Description
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
Time Frame
First 7 days following renal transplantation
Secondary Outcome Measure Information:
Title
Creatinine at 7 and 14 days and at 1, 3 and 6 months
Description
Measure of 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
Title
Cystatin C at 7 and 14 days and at 1, 3 and 6 months
Description
Measure of 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
Title
Symmetrical dimethylarginine at 7 and 14 days and at 1, 3 and 6 months
Description
Measure of 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
Title
Incidence of slow graft function
Description
Slow graft function to be assessed over first 5 days post-transplant
Time Frame
5 days post-transplant
Title
Serum creatinine over time
Description
Measure of Serum creatinine over time
Time Frame
over the duration of follow-up
Title
Composite endpoint
Description
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 Frame
6 months
Title
Time to biopsy-proven kidney allograft rejection
Description
Time to biopsy-proven kidney allograft rejection
Time Frame
6 months
Title
Time to first dialysis or functional delayed graft function and delayed graft function duration
Description
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
Time Frame
30 days
Title
Blood and urine biomarkers for acute kidney injury (AKI)
Description
Serum NGAL, urinary NGAL, α-GST, π-GST, KIM-1 and IL-18
Time Frame
days 2, 7, 14, 28, 90 and 180
Title
Duration of initial hospitalization
Description
Duration of initial hospitalization
Time Frame
6 months
Title
Duration of subsequent readmissions
Description
Duration of subsequent readmissions
Time Frame
6 months
Title
Reason for subsequent readmissions
Description
Reason for subsequent readmissions
Time Frame
6 months
Title
Number of Adverse events (AEs)
Description
Number of Adverse events (AEs)
Time Frame
6 months
Title
Nature of Adverse events (AEs)
Description
Nature of Adverse events (AEs)
Time Frame
6 months
Title
Incidence of infections
Description
Incidence of infections by category and organism
Time Frame
6 months
Title
Rate of primary non-function (permanent lack of function of the allograft)
Time Frame
6 months
Title
Number of dialysis sessions between 0 and 30 days post-transplantation
Description
Number of dialysis sessions between 0 and 30 days post-transplantation
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert M Miller, FRCS MBBS
Organizational Affiliation
OpsonaTherapeutics Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Research Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Research Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
Research Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Research Site
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Research Site
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Research Site
City
Livingston
State/Province
New Jersey
ZIP/Postal Code
07039
Country
United States
Facility Name
Research Site
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Research Site
City
Harrisburg
State/Province
Pennsylvania
ZIP/Postal Code
17105
Country
United States
Facility Name
Research Site
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Research Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Research Site
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Research Site
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Research Site
City
Linz
ZIP/Postal Code
A-4020
Country
Austria
Facility Name
Research Site
City
Brussels
ZIP/Postal Code
1090
Country
Belgium
Facility Name
Research Site
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Research Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Research Site
City
Liege
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Research Site
City
Praha
ZIP/Postal Code
14021
Country
Czech Republic
Facility Name
Research Site
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Research Site
City
Paris
ZIP/Postal Code
75743
Country
France
Facility Name
Research Site
City
Toulouse
ZIP/Postal Code
31409
Country
France
Facility Name
Research Site
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Research Site
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Research Site
City
Bochum
ZIP/Postal Code
44892
Country
Germany
Facility Name
Research Site
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
Research Site
City
Erlangen
ZIP/Postal Code
90154
Country
Germany
Facility Name
Research Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Research Site
City
Koln
ZIP/Postal Code
51109
Country
Germany
Facility Name
Research Site
City
Mannheim
ZIP/Postal Code
68135
Country
Germany
Facility Name
Research Site
City
Munster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Research Site
City
Tubingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Research Site
City
Groningen
ZIP/Postal Code
9700
Country
Netherlands
Facility Name
Research Site
City
Leiden
ZIP/Postal Code
NL-2300 RC
Country
Netherlands
Facility Name
Research Site
City
Nijmegen
ZIP/Postal Code
6525
Country
Netherlands
Facility Name
Research Site
City
Rotterdam
ZIP/Postal Code
3015
Country
Netherlands
Facility Name
Research Site
City
Bydgoszcz
ZIP/Postal Code
85-094
Country
Poland
Facility Name
Research Site
City
Lodz
ZIP/Postal Code
90-153
Country
Poland
Facility Name
Research Site
City
Szczecin
ZIP/Postal Code
70-111
Country
Poland
Facility Name
Research Site
City
Warsaw
ZIP/Postal Code
02507
Country
Poland
Facility Name
Research Site
City
Warszawa
ZIP/Postal Code
02-006
Country
Poland
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Research Site
City
Santander
ZIP/Postal Code
39008
Country
Spain
Facility Name
Research Site
City
Zurich
ZIP/Postal Code
8091
Country
Switzerland
Facility Name
Research Site
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
Research Site
City
Newcastle upon Tyne
ZIP/Postal Code
NE7 7DN
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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