Clinical trial NCT00615966: Phase 2 Study of the Safety of Diannexin in Kidney Transplant Recipients
Official title: A Phase 2, Two-Part Study of the Safety and Tolerability of Diannexin in Kidney Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Kidney Transplantation
Keywords: kidney transplantation
ischemia-reperfusion injury
phosphatidylserine binding
Lead sponsor: Alavita Pharmaceuticals Inc
Sponsor class: INDUSTRY
Collaborators: name: CTI Clinical Trial and Consulting Services
First posted: 2008-02-14
Enrollment: 58
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is evaluate the safety and tolerability of Diannexin in kidney transplant recipients.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety assessments -- physical examinations, vital signs, clinical safety laboratory tests, ECGs, immunogenicity testing, adverse events
timeFrame: 28 days following administration of study medication
Secondary outcomes:
measure: Population pharmacokinetics
timeFrame: Through Hour 48 after dosing
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Livingston
country: United States
facility: St Barnabas Medical Center
state: New Jersey
city: New York
country: United States
facility: New York-Presbyterian Hospital/Weill Cornell Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
city: Madison
country: United States
facility: University of Wisconsin Medical School, Dept of Surgery
state: Wisconsin
Study officials:
affiliation: Emory University
name: Stuart Knechtle, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cheng EY, Sharma VK, Chang C, Ding R, Allison AC, Leeser DB, Suthanthiran M, Yang H. Diannexin decreases inflammatory cell infiltration into the islet graft, reduces beta-cell apoptosis, and improves early graft function. Transplantation. 2010 Oct 15;90(7):709-16. doi: 10.1097/TP.0b013e3181ed55d8.