Delayed Graft FunctionPhase 2NCT01794663
Placebo-Controlled Study to Evaluate the Safety and Efficacy of OPN-305 in Preventing Delayed Renal Graft Function
A Phase 2 study testing OPN-305 in people with Delayed Graft Function, run by Opsona Therapeutics Ltd. at 50 sites in 11 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Delayed Graft Function
- What is being tested?
- OPN-305
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 252 participants
- Where
- 50 sitesin 11 countries
- Study dates
- Oct 2012to 30 Jun 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
- 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
Trial locations and contacts
50 sites in 11 countries.
50 sites in 11 countries
United States14 sites
Research Site
Charleston, South Carolina, 29425
Research Site
Chicago, Illinois, 60612
Research Site
Dallas, Texas, 75246
Research Site
Fort Worth, Texas, 76104
Research Site
Harrisburg, Pennsylvania, 17105
Research Site
Livingston, New Jersey, 07039
Research Site
Los Angeles, California, 90033
Research Site
New Orleans, Louisiana, 70112
Research Site
New Orleans, Louisiana, 70121
Research Site
New York, New York, 10065
Research Site
Richmond, Virginia, 23298
Research Site
Tampa, Florida, 33606
Research Site
The Bronx, New York, 10467
Research Site
Washington D.C., District of Columbia, 20007
Germany10 sites
Research Site
Berlin, 10117
Research Site
Berlin, 13353
Research Site
Bochum, 44892
Research Site
Bonn, 53127
Research Site
Cologne, 51109
Research Site
Erlangen, 90154
Research Site
Heidelberg, 69120
Research Site
Mannheim, 68135
Research Site
Münster, 48149
Research Site
Tübingen, 72076
Poland5 sites
Research Site
Bydgoszcz, 85-094
Research Site
Lodz, 90-153
Research Site
Szczecin, 70-111
Research Site
Warsaw, 02-006
Research Site
Warsaw, 02507
Spain5 sites
Research Site
Barcelona, 08003
Research Site
Barcelona, 08036
Research Site
Barcelona, 08907
Research Site
Madrid, 28041
Research Site
Santander, 39008
Belgium4 sites
Research Site
Brussels, 1090
Research Site
Ghent, 9000
Research Site
Leuven, 3000
Research Site
Liège, 4000
Netherlands4 sites
Research Site
Groningen, 9700
Research Site
Leiden, NL-2300 RC
Research Site
Nijmegen, 6525
Research Site
Rotterdam, 3015
France3 sites
Research Site
Bordeaux, 33076
Research Site
Paris, 75743
Research Site
Toulouse, 31409
United Kingdom2 sites
Research Site
London, SE1 9RT
Research Site
Newcastle upon Tyne, NE7 7DN
About this study
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
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.
Read more
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.
- Conditions
- Delayed Graft Function
- Being tested
- OPN-305, Placebo
- Keywords
- Early kidney graft dysfunction, renal transplantation
- Medical subject headings
- Delayed Graft Function
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OPN-305Drug
Intravenous infusion for 1 hour at start of transplant procedure
PlaceboDrug
Intravenous infusion for 1 hour at start of transplant procedure
| Study group | Role | What they receive |
|---|---|---|
| OPN-305 | Experimental | Not described Receives: Drug: OPN-305 |
| Matching placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: First 7 days following renal transplantation
Secondary outcomes (17)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 5 days post-transplant
Serum creatinine over time
Measure of Serum creatinine over time
Measured: over the duration of follow-up
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
Measured: 6 months
Time to biopsy-proven kidney allograft rejection
Time to biopsy-proven kidney allograft rejection
Measured: 6 months
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
Measured: 30 days
Blood and urine biomarkers for acute kidney injury (AKI)
Serum NGAL, urinary NGAL, α-GST, π-GST, KIM-1 and IL-18
Measured: days 2, 7, 14, 28, 90 and 180
Duration of initial hospitalization
Duration of initial hospitalization
Measured: 6 months
Duration of subsequent readmissions
Duration of subsequent readmissions
Measured: 6 months
Reason for subsequent readmissions
Reason for subsequent readmissions
Measured: 6 months
Number of Adverse events (AEs)
Number of Adverse events (AEs)
Measured: 6 months
Nature of Adverse events (AEs)
Nature of Adverse events (AEs)
Measured: 6 months
Incidence of infections
Incidence of infections by category and organism
Measured: 6 months
Rate of primary non-function (permanent lack of function of the allograft)
Measured: 6 months
Number of dialysis sessions between 0 and 30 days post-transplantation
Number of dialysis sessions between 0 and 30 days post-transplantation
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2013 (estimated)
- Study startOct 2012
- Primary completion30 Jun 2016
- Study completion30 Jun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Delayed Graft FunctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 252 participants (actual)
Sponsor and investigators
- Lead sponsor
- Opsona Therapeutics Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Robert M Miller, FRCS MBBS, Study director, OpsonaTherapeutics Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01794663
- Sponsor's protocol ID
- OPN305-102
- Other IDs
- 2012-001455-39
- Status last verified
- Feb 2017
- First submitted
- 13 Feb 2013
- Last updated
- 16 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01794663
- Acronym / sponsor ID
- OPN305-102
- Conditions
- Delayed Graft Function
- Keywords
- Early kidney graft dysfunction, renal transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 252 participants (actual)
- Lead sponsor
- Opsona Therapeutics Ltd.Industry (pharma, biotech, devices)
- Study start
- Oct 2012
- Primary completion
- 30 Jun 2016 (actual)
- Study completion
- 30 Jun 2016 (actual)
- First posted
- 20 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| OPN-305 | Experimental | Drug: OPN-305 |
| Matching placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- First or second renal transplant recipient - for second renal transplantations;
- Dialysis-dependent at the time of transplantation as documented by:
- The donor kidney must be considered compatible according to local transplant guidelines
- An ECD donor defined as:
- Kidney allograft maintained in cold storage with or without machine perfusion
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OPN-305Intravenous infusion for 1 hour at start of transplant procedure | Drug | OPN-305 |
| PlaceboIntravenous infusion for 1 hour at start of transplant procedure | Drug | Matching placebo |
Primary outcome
Measure of Early Graft Function EGF
Time frame: 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
17 secondary outcomes
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
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
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
Incidence of slow graft function
Time frame: 5 days post-transplant
Serum creatinine over time
Time frame: over the duration of follow-up
Composite endpoint
Time frame: 6 months
Time to biopsy-proven kidney allograft rejection
Time frame: 6 months
Time to first dialysis or functional delayed graft function and delayed graft function duration
Time frame: 30 days
Blood and urine biomarkers for acute kidney injury (AKI)
Time frame: days 2, 7, 14, 28, 90 and 180
Duration of initial hospitalization
Time frame: 6 months
Duration of subsequent readmissions
Time frame: 6 months
Reason for subsequent readmissions
Time frame: 6 months
Number of Adverse events (AEs)
Time frame: 6 months
Nature of Adverse events (AEs)
Time frame: 6 months
Incidence of infections
Time frame: 6 months
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2017.
Related trials for Delayed Graft Function
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Feasibility of Physical Prehabilitation for High-Risk Patients Undergoing Cardiac Surgery Via Sternotomy
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ARGX-117 in Deceased Donor Kidney Transplant Recipients at Risk for Delayed Graft Function
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Drone Transport of Deceased-Donor Kidney Grafts Between Two French Hospitals Before Transplantation: a Pilot Safety Study
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert M Miller, FRCS MBBS study director
OpsonaTherapeutics Ltd.
50 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing OPN-305 in people with Delayed Graft Function, run by Opsona Therapeutics Ltd. at 50 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 50 sites in United States, Germany, Poland, Spain, Belgium and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measure of Early Graft Function EGF (time frame: First 7 days following renal transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2017.