## Protocol Section
### Identification Module
**NCT ID:** NCT00895479

**Acronym:** AdV-VANTAGE

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

**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

#### Organization Study ID Info
**ID:** Ark 103
#### Organization
**Class:** INDUSTRY
**Full Name:** Ark Therapeutics Ltd
### Status Module
#### Completion Date
**Date:** 2011-09

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2010-11-19

**Type:** ESTIMATED

**Last Update Submit Date:** 2010-11-18

**Overall Status:** TERMINATED

#### Primary Completion Date
**Date:** 2011-09

**Type:** ESTIMATED

#### Start Date
**Date:** 2009-04

**Status Verified Date:** 2010-11

#### Study First Post Date
**Date:** 2009-05-08
**Type:** ESTIMATED
**Study First Submit Date:** 2009-05-07
**Study First Submit QC Date:** 2009-05-07
**Why Stopped:** Strategic reasons. Seeking partner for future development.
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Ark Therapeutics Ltd

#### Responsible Party

**Old Name Title:** Director of Research and Development

**Old Organization:** Ark Therapetics Ltd

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**Brief 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.

### Conditions Module

**Conditions:**

- End Stage Renal Disease

**Keywords:**

- End Stage Renal Disease

- ESRD

- Hemodialysis

- Access Graft

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 250

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Graft placement plus Trinam therapy

**Intervention Names:**

- Procedure: Graft placement surgery plus Trinam therapy

**Label:** Trinam

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Graft placement surgery alone

**Label:** Control

**Type:** NO_INTERVENTION

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Trinam

**Description:** Trinam arm: graft placement surgery plus 1ml perivascular administration of Trinam vector.

Control arm: graft placement surgery

**Name:** Graft placement surgery plus Trinam therapy

**Type:** PROCEDURE

### Outcomes Module

#### Primary Outcomes

**Measure:** Primary Unassisted Patency

**Time Frame:** 18 Months

#### Secondary Outcomes

**Measure:** Graft Survival. Number and rate of graft interventions.

**Time Frame:** 2.5 years

### Eligibility Module

**Eligibility 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.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Long Beach

**Country:** United States

**Facility:** Long Beach VA Healthcare System

**State:** California

**Zip:** CA 90822

**Location 2:**

**City:** Paducah

**Country:** United States

**Facility:** Four Rivers Clinical Research Inc

**State:** Kentucky

**Zip:** KY 42003

**Location 3:**

**City:** Baton Rouge

**Country:** United States

**Facility:** Baton Rouge General Hospital

**State:** Louisiana

**Zip:** LA 70809

**Location 4:**

**City:** Shreveport

**Country:** United States

**Facility:** Louisiana State University Health Sciences Center

**State:** Louisiana

**Zip:** LA 71103

**Location 5:**

**City:** St Louis

**Country:** United States

**Facility:** Washington University School of Medicine

**State:** Missouri

**Zip:** MO 63110

**Location 6:**

**City:** New York

**Country:** United States

**Facility:** Mount Sinai Medical Center

**State:** New York

**Zip:** NY 10029

**Location 7:**

**City:** New York

**Country:** United States

**Facility:** St Luke's Roosevelt Hospital

**State:** New York

**Zip:** NY10025

**Location 8:**

**City:** Durham

**Country:** United States

**Facility:** Duke University Medical Center

**State:** North Carolina

**Zip:** NC 27710

**Location 9:**

**City:** Cincinnati

**Country:** United States

**Facility:** University of Cincinnati

**State:** Ohio

**Zip:** OH 45267

**Location 10:**

**City:** Columbus

**Country:** United States

**Facility:** Ohio State University Division of Nephrology

**State:** Ohio

**Zip:** OH 43210

**Location 11:**

**City:** Lubbock

**Country:** United States

**Facility:** Texas Tech University Medical Center

**State:** Texas

**Zip:** TX 79415

**Location 12:**

**City:** Seattle

**Country:** United States

**Facility:** Harborview Medical Center

**State:** Washington

**Zip:** WA 98104

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000014570

- Term: Urologic Diseases

- ID: D000052776

- Term: Female Urogenital Diseases

- ID: D000005261

- Term: Female Urogenital Diseases and Pregnancy Complications

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000052801

- Term: Male Urogenital Diseases

- ID: D000051436

- Term: Renal Insufficiency, Chronic

- ID: D000051437

- Term: Renal Insufficiency

- ID: D000002908

- Term: Chronic Disease

- ID: D000020969

- Term: Disease Attributes

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: BC01

- Name: Infections

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10698

- Name: Kidney Diseases

- Relevance: HIGH

- As Found: Renal Disease

- ID: M10699

- Name: Kidney Failure, Chronic

- Relevance: HIGH

- As Found: End Stage Renal Disease

- ID: M3610

- Name: Adenoviridae Infections

- Relevance: LOW

- As Found: Unknown

- ID: M26718

- Name: Renal Insufficiency

- Relevance: LOW

- As Found: Unknown

- ID: M17319

- Name: Urologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27093

- Name: Female Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14127

- Name: Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M8399

- Name: Female Urogenital Diseases and Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M27095

- Name: Male Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M26717

- Name: Renal Insufficiency, Chronic

- Relevance: LOW

- As Found: Unknown

- ID: M6147

- Name: Chronic Disease

- Relevance: LOW

- As Found: Unknown

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

- ID: T1303

- Name: Chronic Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000007674

- Term: Kidney Diseases

- ID: D000007676

- Term: Kidney Failure, Chronic

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M18681

- Name: Endothelial Growth Factors

- Relevance: LOW

- As Found: Unknown

- ID: M11900

- Name: Mitogens

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
