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

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

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

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: Diannexin; Drug: Diannexin; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • St Barnabas Medical Center
  • New York
    • New York, New York, United States, 10065
      • New York-Presbyterian Hospital/Weill Cornell Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Baptist Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Medical School, Dept of Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Diannexin; single dose, 200 µg/kg IV; Drug: Diannexin; Single dose, 400 µg/kg IV
Experimental: 2	Drug: Diannexin; single dose, 200 µg/kg IV; Drug: Diannexin; Single dose, 400 µg/kg IV
Placebo Comparator: 3	Drug: Placebo; Single dose, IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	Time Frame
Population pharmacokinetics	Through Hour 48 after dosing

Collaborators and Investigators

• Sponsor: Alavita Pharmaceuticals Inc
• Collaborators: CTI Clinical Trial and Consulting Services
• Investigators: Principal Investigator: Stuart Knechtle, MD, Emory University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: February 1, 2008
• First Submitted That Met QC Criteria: February 1, 2008
• First Posted (Estimate): February 14, 2008

Study Record Updates

• Last Update Posted (Estimate): June 29, 2011
• Last Update Submitted That Met QC Criteria: June 24, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: kidney transplantation; ischemia-reperfusion injury; phosphatidylserine binding
• Other Study ID Numbers: DAV-CL002