Efficiency, Safety and Portability of Neovasculgen

Study Overview
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Brief Summary
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In 2010, we completed a phase 1 to 2a clinical trial of pCMV-vegf165 in patients with chronic lower limb ischemia (stage 2a to 3 according to Fontaine classification modified by A. V. Pokrovsky) who were not suitable for reconstructive surgery or endovascular treatment. This study demonstrated the safety, feasibility, and short-term(3 months) efficacy of pCMV-vegf165 gene transfer,12,13which lead to conducting a phase 2b to 3 multicenter clinical trial. The study was conducted under the control of the Russian Ministry of Health and was completed in 2011. Patients enrolled in the study were subjected to a 6-month

Detailed Description
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We conducted a phase 2b/3 multicenter randomized controlled clinical trial of the intramuscular transfer of a plasmid DNA encoding vascular endothelial growth factor (VEGF) 165 with cytomegalovirus promotor (CMV) in patients with atherosclerotic lower limb ischemia. A total of 100 patients were enrolled in the study, that is, 75 patients were randomized into the test group and received 2 intramuscular injections of 1.2 mg of pCMV- vegf165, 14 days apart together with standard pharmacological treatment. In all, 25 patients were randomized into the control group and received standard treatment only. The following end points were evaluated within the first 6 months of the study and during a 1.5-year additional follow-up period: pain-free walking distance (PWD), ankle-brachial index (ABI), and blood flow velocity (BFV).

Official Title
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Phase 3 Study of Efficiency, Safety and Portability of Gene Therapy Drug Neovasculgen (DNA Encoding the 165-amino-acid Isoform of Human Vascular Endothelial Growth Factor (pCMV - VEGF165) for Peripheral Arterial Disease Complex Treatment

Conditions
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Peripheral Arterial Disease

Intervention / Treatment
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* Drug: Neovasculgen (Cambiogeneplasmid)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age more than 40 years; a history of stable claudication for at least 3 months; stage 2 to 3 chronic ischemia according to Fontaine classification (modified by A. V. Pokrovsky); presence of hemodynamically significant (stenosis >70% and/or occlusion) diffuse lesions of the interior and (or) posterior tibial arteries (distal lesion); voluntary informed consent signed and dated by the patient. Exclusion Criteria: chronic lower limb ischemia of nonatherosclerotic genesis; stage 4 chronic ischemia according to Fontaine classification modified by A. V. Pokrovsky (ischemic ulcers and necrotic lesions); severe concomitant pathology with life expectancy <1 year; infectious diseases, history of cancer, or suspected malignancy;

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neovasculgen<br>DNA encoding the 165-amino-acid isoform of human vascular endothelial growth factor (pCMV - VEGF165) | Drug: Neovasculgen (Cambiogeneplasmid)<br>* treatment<br>* Other names: Neovasculgen;|
| No Intervention: Control<br>Control therapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain-free walking distance. | The PWD was determined using a treadmill test with reduced initial speed (1 km/h), as the majority of elderly patients were unable to perform Gardner test or its equivalents. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ankle-brachial index | The ankle-brachial pressure index (ABPI) or ankle-brachial index (ABI) is the ratio of the blood pressure at the ankle to the blood pressure in the upper arm (brachium). Compared to the arm, lower blood pressure in the leg is an indication of blocked arteries due to peripheral artery disease (PAD). | 6 months | 
| Transcutaneous oximetry | Transcutaneous oximetry, tcpO2 or TCOM, is a local, non-invasive measurement reflecting the amount of O2 that has diffused from the capillaries, through the epidermis. | 6 months | 
| quality of life | SF-36 is a set of generic, coherent, and easily administered quality-of-life measures. These measures rely upon patient self-reporting and are now widely utilized by managed care organizations and by Medicare for routine monitoring and assessment of care outcomes in adult patients. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PAD, CLI, stage 2a-3 of Pokrovsky-Fonteine