Phase 2 Study of the Safety of Diannexin in Kidney Transplant Recipients

Study Overview
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Brief Summary
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The purpose of this study is evaluate the safety and tolerability of Diannexin in kidney transplant recipients.

Detailed Description
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Ischemia-reperfusion injury, which occurs when the blood supply to an organ, or part of an organ, is cut off and subsequently restored, is an important clinical problem in the organ transplant setting. Diannexin, a recombinant form of the endogenous human Annexin V protein, is in development as a therapeutic agent designed to prevent ischemia-reperfusion injury following organ transplantation. Pharmacology studies indicate that Diannexin has protective effect in various ischemia-reperfusion injury and organ transplantation models. Diannexin binds to phosphatidylserine on cell surfaces, which is believed to underlie its ability to attenuate ischemia-reperfusion injury. In a completed Phase 1 trial, Diannexin was judged safe and well tolerated in healthy adult subjects. The present study is designed to determine the safety and tolerability of single escalating doses of Diannexin in kidney transplant recipients.

Official Title
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A Phase 2, Two-Part Study of the Safety and Tolerability of Diannexin in Kidney Transplant Recipients

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: Diannexin
* Drug: Placebo
* Drug: Diannexin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Scheduled to receive a kidney transplant from a deceased expanded criterion donor (ECD) or a donor cardiac death (DCD) donor that was exposed to no more than 36 hr of cold ischemia prior to transplantation, or scheduled to receive a kidney transplant from a standard criterion donor (SCD) that was exposed to 24-36 hr of cold ischemia prior to transplantation Willing to use adequate contraception for at least 4 weeks after dosing Willing and able to provide written Informed Consent and to comply with the requirements of the study Exclusion Criteria: If female, subject is pregnant or lactating Known bleeding diathesis INR at Screening > 1.5 Platelet count at Screening below LLN and judged clinically significant Use of Plavix, anticoagulants other than aspirin, antithrombotics, and/or blood-thinning agents within 10 days prior to study entry Previous receipt of an organ transplant Will receive concurrent transplant of any additional organ(s) Clinically significant active infection at study entry Surgery within 2 weeks prior to study entry Believed to have used an illicit drug and/or abused alcohol within 3 months prior to study entry Presence of a psychiatric illness that might interfere with study participation Cancer, other than basal cell or squamous cell cancer of the skin, within 2 years prior to study entry Scheduled to receive a kidney transplant from a low risk donor Currently participation, or participated within 30 days prior to study entry, in an investigational drug study Known allergy to kanamycin History or presence of any medical condition or disease that could place the subject an unacceptable risk for study participation

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Diannexin<br>* single dose, 200 µg/kg IV<br>|
| Experimental: 2<br> | Drug: Diannexin<br>* Single dose, 400 µg/kg IV<br>|
| Placebo Comparator: 3<br> | Drug: Placebo<br>* Single dose, IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessments -- physical examinations, vital signs, clinical safety laboratory tests, ECGs, immunogenicity testing, adverse events |  | 28 days following administration of study medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Population pharmacokinetics |  | Through Hour 48 after dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kidney transplantation, ischemia-reperfusion injury, phosphatidylserine binding