Clinical trial NCT01794663: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Delayed Graft Function
Keywords: Early kidney graft dysfunction
renal transplantation
Lead sponsor: Opsona Therapeutics Ltd.
Sponsor class: INDUSTRY
First posted: 2013-02-20
Enrollment: 252
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: Measure of Early Graft Function EGF
timeFrame: First 7 days following renal transplantation
Secondary outcomes:
measure: Creatinine at 7 and 14 days and at 1, 3 and 6 months
timeFrame: 7 and 14 days and at 1, 3 and 6 months
measure: Cystatin C at 7 and 14 days and at 1, 3 and 6 months
timeFrame: 7 and 14 days and at 1, 3 and 6 months
measure: Symmetrical dimethylarginine at 7 and 14 days and at 1, 3 and 6 months
timeFrame: 7 and 14 days and at 1, 3 and 6 months
measure: Incidence of slow graft function
timeFrame: 5 days post-transplant
measure: Serum creatinine over time
timeFrame: over the duration of follow-up
measure: Composite endpoint
timeFrame: 6 months
measure: Time to biopsy-proven kidney allograft rejection
timeFrame: 6 months
measure: Time to first dialysis or functional delayed graft function and delayed graft function duration
timeFrame: 30 days
measure: Blood and urine biomarkers for acute kidney injury (AKI)
timeFrame: days 2, 7, 14, 28, 90 and 180
measure: Duration of initial hospitalization
timeFrame: 6 months
measure: Duration of subsequent readmissions
timeFrame: 6 months
measure: Reason for subsequent readmissions
timeFrame: 6 months
measure: Number of Adverse events (AEs)
timeFrame: 6 months
measure: Nature of Adverse events (AEs)
timeFrame: 6 months
measure: Incidence of infections
timeFrame: 6 months
measure: Rate of primary non-function (permanent lack of function of the allograft)
timeFrame: 6 months
measure: Number of dialysis sessions between 0 and 30 days post-transplantation
timeFrame: 30 days
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: New Orleans
country: United States
facility: Research Site
state: Louisiana
city: New Orleans
country: United States
facility: Research Site
state: Louisiana
city: Livingston
country: United States
facility: Research Site
state: New Jersey
city: Bronx
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Harrisburg
country: United States
facility: Research Site
state: Pennsylvania
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Fort Worth
country: United States
facility: Research Site
state: Texas
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Linz
country: Austria
facility: Research Site
city: Brussels
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Liege
country: Belgium
facility: Research Site
city: Praha
country: Czech Republic
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bochum
country: Germany
facility: Research Site
city: Bonn
country: Germany
facility: Research Site
city: Erlangen
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Koln
country: Germany
facility: Research Site
city: Mannheim
country: Germany
facility: Research Site
city: Munster
country: Germany
facility: Research Site
city: Tubingen
country: Germany
facility: Research Site
city: Groningen
country: Netherlands
facility: Research Site
city: Leiden
country: Netherlands
facility: Research Site
city: Nijmegen
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Szczecin
country: Poland
facility: Research Site
city: Warsaw
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: Zurich
country: Switzerland
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Research Site
Study officials:
affiliation: OpsonaTherapeutics Ltd.
name: Robert M Miller, FRCS MBBS
role: STUDY_DIRECTOR
References: