Adenovirus Vascular Endothelial Growth Factor (VEGF) Therapy in Vascular Access - Novel Trinam AGainst Control Evidence (AdV-VANTAGE)

A Phase III, Randomized, Controlled, Open Label, Multicenter Study of the Efficacy and Safety of Trinam® (EG004); an Assessment of Primary Unassisted Patency and Survival of Vascular Access Grafts in Hemodialysis Patients With End Stage Renal Disease

Patients in renal failure on hemodialysis depend on adequate and sustained vascular access. This can be achieved by surgical placement of a synthetic polytetrafluoroethylene (PTFE) graft. These patients frequently experience graft complications arising from the development of smooth muscle cell (SMC) neointimal hyperplasia in the proximity of the graft-vein anastomosis. Such complications eventually lead to stenosis, access thrombosis and graft failure. Trinam® is being developed to prolong graft survival. It is a combination product consisting of a replication deficient Adenovirus containing the human Vascular Endothelial Growth Factor D (Ad-VEGF-D) gene and a biodegradable local delivery device (collar) made of collagen. At the end of the surgical procedure to insert the PTFE graft the collagen collar is applied around the anastomosis and sealed with a collagen surgical sealant. This procedure creates a reservoir between the site of anastomosis and the collagen collar. The adenoviral vector is then injected into this reservoir, localizing the expression of the transgene to the site of the anastomosis. Expression of VEGF-D has been shown to have a vascular protective role and inhibit SMC neointimal proliferation, therefore expression of VEGF-D should prolong graft survival.

Study Overview

• Status: Terminated
• Conditions: End Stage Renal Disease
• Intervention / Treatment: Procedure: Graft placement surgery plus Trinam therapy

• Study Type: Interventional
• Enrollment (Anticipated): 250
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, CA 90822
      • Long Beach VA Healthcare System
  • Kentucky
    • Paducah, Kentucky, United States, KY 42003
      • Four Rivers Clinical Research Inc
  • Louisiana
    • Baton Rouge, Louisiana, United States, LA 70809
      • Baton Rouge General Hospital
    • Shreveport, Louisiana, United States, LA 71103
      • Louisiana State University Health Sciences Center
  • Missouri
    • St Louis, Missouri, United States, MO 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, NY 10029
      • Mount Sinai Medical Center
    • New York, New York, United States, NY10025
      • St Luke's Roosevelt Hospital
  • North Carolina
    • Durham, North Carolina, United States, NC 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, OH 45267
      • University of Cincinnati
    • Columbus, Ohio, United States, OH 43210
      • Ohio State University Division of Nephrology
  • Texas
    • Lubbock, Texas, United States, TX 79415
      • Texas Tech University Medical Center
  • Washington
    • Seattle, Washington, United States, WA 98104
      • Harborview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with end stage renal disease undergoing either initial placement or replacement (after failure of previous vascular access) of an end-to-side or end-to-end 6.0 mm synthetic PTFE arteriovenous hemodialysis access arm graft.
• Male or female aged 18 years or over.
• Patients who signed the informed consent form.
• Patients who are expected to undergo dialysis at nominated facilities for the duration of the study.
• Patients who have agreed to participate in the additional four year gene therapy safety monitoring.
• Patients who are willing to agree they will not have a kidney transplant for four weeks post treatment with Trinam®.
• Patients who have undergone arterial and venous mapping to ensure an adequate and appropriate access site is available for placement of either an end-to-side or an end-to-end 6.0 mm synthetic PTFE arteriovenous hemodialysis access arm graft with or without the addition of Trinam®.

Exclusion Criteria:

• Patients who are unable to understand and sign the consent form.
• Patients undergoing surgical revision of an existing graft.
• Exclude patients from the study if they have moderate or severe macular edema moderate or severe proliferative diabetic retinopathy
• Current diagnosis of cancer with exception of non-melanoma skin cancers.
• Hepatic dysfunction defined as AST and / or ALT > 2 times the Upper Limit of Normal.
• Diabetic patients with Hemoglobin A1C value of >10%.
• White blood cell (WBC) count < 2.0 x 109/L.
• Prior anticoagulant therapy within 14 days prior to surgery is an exclusion.
• Known sensitivity to collagen.
• Pregnancy, lactation or lack of effective contraception both in women and in men of childbearing potential.
• Previous participation in any Trinam® study.
• Receipt of any investigational drug within 30 days prior to study enrollment or participation in any concurrently running trial involving investigational intervention.
• Any medical or psychiatric condition that compromises the ability to participate in the study.
• Known or suspected drug or alcohol abuse in the past six months.
• Life expectancy of less than one year.
• Known immunodeficiency disease.
• Known chronic hepatitis of viral or non-viral etiology and / or a history of decompensated liver failure of any etiology.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trinam; Graft placement plus Trinam therapy	Procedure: Graft placement surgery plus Trinam therapy; Trinam arm: graft placement surgery plus 1ml perivascular administration of Trinam vector. Control arm: graft placement surgery
No Intervention: Control; Graft placement surgery alone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Primary Unassisted Patency	18 Months

Secondary Outcome Measures

Outcome Measure	Time Frame
Graft Survival. Number and rate of graft interventions.	2.5 years

Collaborators and Investigators

• Sponsor: Ark Therapeutics Ltd

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Anticipated): September 1, 2011
• Study Completion (Anticipated): September 1, 2011

Study Registration Dates

• First Submitted: May 7, 2009
• First Submitted That Met QC Criteria: May 7, 2009
• First Posted (Estimate): May 8, 2009

Study Record Updates

• Last Update Posted (Estimate): November 19, 2010
• Last Update Submitted That Met QC Criteria: November 18, 2010
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Keywords: End Stage Renal Disease; ESRD; Hemodialysis; Access Graft
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: Ark 103

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No