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

End Stage Renal Disease Clinical Trial

— AdV-VANTAGE  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00895479
• Other study ID #: Ark 103
• Status: Terminated
• Phase: Phase 3
• First received: May 7, 2009
• Last updated: November 18, 2010
• Start date: April 2009
• Est. completion date: September 2011

Study information

• Verified date: November 2010
• Source: Ark Therapeutics Ltd
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 250
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• End Stage Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

Procedure:
• Graft placement surgery plus Trinam therapy
Trinam arm: graft placement surgery plus 1ml perivascular administration of Trinam vector. Control arm: graft placement surgery

Locations

Country	Name	City	State
United States	Baton Rouge General Hospital	Baton Rouge	Louisiana
United States	University of Cincinnati	Cincinnati	Ohio
United States	Ohio State University Division of Nephrology	Columbus	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Long Beach VA Healthcare System	Long Beach	California
United States	Texas Tech University Medical Center	Lubbock	Texas
United States	Mount Sinai Medical Center	New York	New York
United States	St Luke's Roosevelt Hospital	New York	New York
United States	Four Rivers Clinical Research Inc	Paducah	Kentucky
United States	Harborview Medical Center	Seattle	Washington
United States	Louisiana State University Health Sciences Center	Shreveport	Louisiana
United States	Washington University School of Medicine	St Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Ark Therapeutics Ltd

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Unassisted Patency		18 Months	No
Secondary	Graft Survival. Number and rate of graft interventions.		2.5 years	No