Efficacy and Safety Study of NV1FGF in Patients With Severe Peripheral Artery Occlusive Disease

Study Overview
=================
Brief Summary
-----------------
This study is a double-blind study to evaluate the efficacy and safety of NV1FGF, a pCOR plasmid constructed by inserting the gene coding for the FGF compared to placebo in patients with severe Peripheral Arterial Occlusive Disease, Fontaine's stage IV. The efficacy was assessed by the complete healing of at least one ulcer in the treated limb, 25 week post-baseline and secondary by the rate of amputation and death.

Official Title
-----------------
A Phase II, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Efficacy and Safety Study of NV1FGF in Patients With Severe Peripheral Artery Occlusive Disease.

Conditions
-----------------
Peripheral Arterial Disease

Intervention / Treatment
-----------------
* Drug: XRP0038 (NV1FGF)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Outpatients with severe Peripheral Artery Occlusive Disease defined as Rutherford's Grade III, category 5 or 6, or Fontaine's stage IV. Trophic lesions with no signs of healing (no reduction in ulcer size or depth) for at least 2 weeks prior to first study treatment administration (Day 1). Patients with objective evidence of peripheral vascular disease (resting ankle pressure < 70 mmHg and/or toe pressure < 50 mmHg, and/or resting ankle-brachial index (ABI) < 0.4 and/or resting toe-brachial index (TBI) < 0.3 and/or metatarsal pulse volume recording (PVR) flat or barely pulsatile) in the diseased limb on two consecutive examinations performed at least 1 week apart. Demonstration or documentation (historical data not older than 6 months prior to first study treatment administration) of total occlusion of the affected limb of one or more of the iliac, superficial femoral, popliteal and/or one or more infrapopliteal arteries as assessed by angiography. Life expectancy > 6 months from the first study treatment administration. Poor/not candidates for revascularization (patients suitable for revascularization but with a high risk of failure/ amputation/ or patients not suitable for revascularization). Exclusion Criteria: Previous or current history of malignant disease. Patients who had successful tumor resection or radio-chemotherapy more than 5 years prior to inclusion in the study and no recurrence will be allowed for inclusion. Suspicion of malignant disease (abnormal X ray,positive. stool hemoccult, positive Prostate Specific Antigen , abnormal mammography, papanicolaou smear of Class IV or Class V characterization. Lower extremity surgery : bypass/angioplasty of the leg to be treated within 2 months prior to the first administration of study treatment (Day 1). Active proliferative retinopathy. Buerger's disease

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: XRP0038 (NV1FGF)|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary efficacy parameter: ulcer healing. |  |  | 
| Ulcers will be evaluated at each visit primarily by collecting quantitative and qualitative information. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemodynamic parameters:ABI, TcPO2 |  |  | 
| Pain |  |  | 
| Amputation (Date of amputation, Indication for amputation, amputation level (minor and major) |  |  | 
| Death |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Gene Therapy, PAOD, CLI