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

This study has been terminated.
(Strategic reasons. Seeking partner for future development.)
Sponsor:
Information provided by:
Ark Therapeutics Ltd
ClinicalTrials.gov Identifier:
NCT00895479
First received: May 7, 2009
Last updated: November 18, 2010
Last verified: November 2010
  Purpose

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.


Condition Intervention Phase
End Stage Renal Disease
Procedure: Graft placement surgery plus Trinam therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Ark Therapeutics Ltd:

Primary Outcome Measures:
  • Primary Unassisted Patency [ Time Frame: 18 Months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Graft Survival. Number and rate of graft interventions. [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 250
Study Start Date: April 2009
Estimated Study Completion Date: September 2011
Estimated Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00895479

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

No publications provided

Responsible Party: Director of Research and Development, Ark Therapetics Ltd
ClinicalTrials.gov Identifier: NCT00895479     History of Changes
Other Study ID Numbers: Ark 103
Study First Received: May 7, 2009
Last Updated: November 18, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Ark Therapeutics Ltd:
End Stage Renal Disease
ESRD
Hemodialysis
Access Graft

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Endothelial Growth Factors
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 15, 2014