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

NCT01794663 | Completed Phase 2 DMC

• 2 other identifiers: OPN305-1022012-001455-39
• Study Type: interventional
• Target: 252
• Locations: 11 countries
• Sites: 50

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.

Conditions

Delayed Graft Function

Keywords

Early kidney graft dysfunction; renal transplantation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (17)

• Creatinine at 7 and 14 days and at 1, 3 and 6 months

  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

• 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

• Incidence of slow graft function

  5 days post-transplant

• Serum creatinine over time

  over the duration of follow-up

Study Arms (2)

OPN-305

EXPERIMENTAL

Drug: OPN-305

Matching placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

OPN-305 DRUG

Intravenous infusion for 1 hour at start of transplant procedure

OPN-305

Placebo DRUG

Intravenous infusion for 1 hour at start of transplant procedure

Matching placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Opsona Therapeutics Ltd.: lead

Study Sites (50)

Research Site

Los Angeles, California, 90033, United States

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Washington D.C., District of Columbia, 20007, United States

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Tampa, Florida, 33606, United States

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Chicago, Illinois, 60612, United States

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New Orleans, Louisiana, 70112, United States

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New Orleans, Louisiana, 70121, United States

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Livingston, New Jersey, 07039, United States

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New York, New York, 10065, United States

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The Bronx, New York, 10467, United States

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Harrisburg, Pennsylvania, 17105, United States

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Charleston, South Carolina, 29425, United States

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Dallas, Texas, 75246, United States

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Fort Worth, Texas, 76104, United States

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Richmond, Virginia, 23298, United States

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Linz, A-4020, Austria

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Brussels, 1090, Belgium

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Ghent, 9000, Belgium

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Leuven, 3000, Belgium

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Liège, 4000, Belgium

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Prague, 14021, Czechia

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Bordeaux, 33076, France

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Paris, 75743, France

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Toulouse, 31409, France

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Berlin, 10117, Germany

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Berlin, 13353, Germany

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Bochum, 44892, Germany

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Bonn, 53127, Germany

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Cologne, 51109, Germany

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Erlangen, 90154, Germany

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Heidelberg, 69120, Germany

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Mannheim, 68135, Germany

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Münster, 48149, Germany

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Tübingen, 72076, Germany

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Groningen, 9700, Netherlands

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Leiden, NL-2300 RC, Netherlands

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Nijmegen, 6525, Netherlands

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Rotterdam, 3015, Netherlands

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Bydgoszcz, 85-094, Poland

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Lodz, 90-153, Poland

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Szczecin, 70-111, Poland

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Warsaw, 02-006, Poland

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Warsaw, 02507, Poland

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Barcelona, 08003, Spain

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Barcelona, 08036, Spain

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Barcelona, 08907, Spain

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Madrid, 28041, Spain

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Santander, 39008, Spain

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Zurich, 8091, Switzerland

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London, SE1 9RT, United Kingdom

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Newcastle upon Tyne, NE7 7DN, United Kingdom

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MeSH Terms

Conditions

Delayed Graft Function

Interventions

tomaralimab

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Robert M Miller, FRCS MBBS

  OpsonaTherapeutics Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2013
• First Posted: February 20, 2013
• Study Start: October 1, 2012
• Primary Completion: June 30, 2016
• Study Completion: June 30, 2016
• Last Updated: February 16, 2017

Record last verified: 2017-02

Locations

BE (4); AU (1); CZ (1); NL (4); CH (1); DE (10); PL (5); US (14); FR (3); GB (2); ES (5)