Clinical trial NCT03068585: Efficiency, Safety and Portability of Neovasculgen
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Peripheral Arterial Disease
Keywords: PAD
CLI
stage 2a-3 of Pokrovsky-Fonteine
Lead sponsor: Human Stem Cell Institute, Russia
Sponsor class: OTHER
First posted: 2017-03-03
Enrollment: 100
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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;

Primary outcomes:
measure: Pain-free walking distance.
timeFrame: 6 months
Secondary outcomes:
measure: Ankle-brachial index
timeFrame: 6 months
measure: Transcutaneous oximetry
timeFrame: 6 months
measure: quality of life
timeFrame: 6 months
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Russian National Surgery Center by Petrovsky
state: Central Russia
city: Ryazan
country: Russian Federation
facility: Ryazansky State Medical University
state: Central Russia
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl State Medical Academy
state: Central Russia
Study officials:
References:
citation: Deev RV, Bozo IY, Mzhavanadze ND, Voronov DA, Gavrilenko AV, Chervyakov YV, Staroverov IN, Kalinin RE, Shvalb PG, Isaev AA. pCMV-vegf165 Intramuscular Gene Transfer is an Effective Method of Treatment for Patients With Chronic Lower Limb Ischemia. J Cardiovasc Pharmacol Ther. 2015 Sep;20(5):473-82. doi: 10.1177/1074248415574336. Epub 2015 Mar 13.
citation: Deev R, Plaksa I, Bozo I, Mzhavanadze N, Suchkov I, Chervyakov Y, Staroverov I, Kalinin R, Isaev A. Results of 5-year follow-up study in patients with peripheral artery disease treated with PL-VEGF165 for intermittent claudication. Ther Adv Cardiovasc Dis. 2018 Sep;12(9):237-246. doi: 10.1177/1753944718786926. Epub 2018 Jul 11.