PMID- 28050885
OWN - NLM
STAT- MEDLINE
DCOM- 20180227
LR  - 20240222
IS  - 1179-187X (Electronic)
IS  - 1175-3277 (Print)
IS  - 1175-3277 (Linking)
VI  - 17
IP  - 3
DP  - 2017 Jun
TI  - Results of an International Postmarketing Surveillance Study of pl-VEGF165 Safety 
      and Efficacy in 210 Patients with Peripheral Arterial Disease.
PG  - 235-242
LID - 10.1007/s40256-016-0210-3 [doi]
AB  - INTRODUCTION: The effective treatment of chronic lower limb ischemia is one of 
      the most challenging issues confronting vascular surgeons. Current 
      pharmacological therapies play an auxiliary role and cannot prevent disease 
      progression, and new treatment methods are needed. pl-VEGF165, a gene therapy 
      drug, was approved in Russia for the treatment of atherosclerotic peripheral 
      arterial disease (PAD) after clinical studies in 2011. The study drug is an 
      original gene construction in which pl-VEGF165 1.2 mg is the active substance. 
      OBJECTIVE: This postmarketing surveillance study was undertaken to evaluate the 
      safety (identification of uncommon side effects) and efficacy of gene therapy in 
      patients in routine clinical practice. METHODS: In total, 210 patients with stage 
      II-III chronic limb ischemia (according to the Fontaine classification modified 
      by AV Pokrovsky) in 33 healthcare facilities in Russia and the Ukraine were 
      enrolled in the study. The control group (n = 60) received conservative therapy 
      without prostaglandins and prostacyclins, and the treatment group (n = 150) 
      received treatment with pl-VEGF165 as two intramuscular injections for a total 
      dose of 2.4 mg. Pain-free walking distance (PWD) (the primary efficacy criterion 
      for Fontaine stages II-III), blood flow linear velocity (BFLV), and 
      ankle-brachial index (ABI) were monitored for 6 months. The safety of pl-VEGF165 
      gene transfer in terms of the trial protocol was initially evaluated 6 months 
      after the start of the study; adverse events (AEs) and serious adverse events 
      (SAEs) were recorded during both routine visits and unscheduled requests for 
      medical care. RESULTS: Overall, PWD increased by 177%, from 100.3 +/- 6.9 to 
      277.1 +/- 16.2 m (p = 0.0001), in the treatment group, whereas the mean value was 
      unchanged in the control group (p = 0.218). Both BFLV and ABI values increased by 
      24% (p = 0.0001) in the treatment group but decreased in the control group. The 
      greatest therapeutic effect was observed for stage III disease: PWD increased by 
      683% (p = 0.0001). No angiogenic therapy-related AEs or side effects were 
      recorded, and target limb salvage was 96 and 97% in the treatment and control 
      groups, respectively. The results obtained in this study are not significantly 
      different from those observed in the phase IIb/III registration clinical study 
      completed in 2011. CONCLUSION: pl-VEGF165 intramuscular gene transfer is an 
      effective treatment for moderate to severe claudication due to chronic lower limb 
      ischemia in routine clinical practice. ClinicalTrials.gov identifier: 
      NCT02369809.
FAU - Deev, Roman
AU  - Deev R
AD  - Human Stem Cells Institute, Bld. 2, 3 Gubkina Str., P.O. box 373, Moscow, 119333, 
      Russia.
AD  - Ryazan State I.P. Pavlov Medical University, Ryazan, Russia.
FAU - Plaksa, Igor
AU  - Plaksa I
AD  - Human Stem Cells Institute, Bld. 2, 3 Gubkina Str., P.O. box 373, Moscow, 119333, 
      Russia. i.plaksa2014@yandex.ru.
AD  - Pavlov First Saint-Petersburg State Medical University, Saint Petersburg, Russia. 
      i.plaksa2014@yandex.ru.
FAU - Bozo, Ilia
AU  - Bozo I
AD  - Human Stem Cells Institute, Bld. 2, 3 Gubkina Str., P.O. box 373, Moscow, 119333, 
      Russia.
AD  - Moscow State University of Medicine and Dentistry, Moscow, Russia.
FAU - Isaev, Artur
AU  - Isaev A
AD  - Human Stem Cells Institute, Bld. 2, 3 Gubkina Str., P.O. box 373, Moscow, 119333, 
      Russia.
LA  - eng
SI  - ClinicalTrials.gov/NCT02369809
PT  - Journal Article
PL  - New Zealand
TA  - Am J Cardiovasc Drugs
JT  - American journal of cardiovascular drugs : drugs, devices, and other 
      interventions
JID - 100967755
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - Aged
MH  - Ankle Brachial Index/methods
MH  - Extremities/*physiopathology
MH  - Female
MH  - Genetic Therapy/methods
MH  - Humans
MH  - Ischemia/*drug therapy
MH  - Male
MH  - Peripheral Arterial Disease/*drug therapy
MH  - Product Surveillance, Postmarketing
MH  - Treatment Outcome
MH  - Vascular Endothelial Growth Factor A/*adverse effects/*therapeutic use
PMC - PMC5435773
COIS- FUNDING: This study was funded by the Human Stem Cells Institute OJSC, Moscow, 
      Russia. CONFLICT OF INTEREST: A Isaev, I Bozo, R Deev, and I Plaksa are employees 
      of the OJSC Human Stem Cells Institute. A Isaev holds shares in the Human Stem 
      Cells Institute OJSC.
EDAT- 2017/01/05 06:00
MHDA- 2018/02/28 06:00
PMCR- 2017/01/03
CRDT- 2017/01/05 06:00
PHST- 2017/01/05 06:00 [pubmed]
PHST- 2018/02/28 06:00 [medline]
PHST- 2017/01/05 06:00 [entrez]
PHST- 2017/01/03 00:00 [pmc-release]
AID - 10.1007/s40256-016-0210-3 [pii]
AID - 210 [pii]
AID - 10.1007/s40256-016-0210-3 [doi]
PST - ppublish
SO  - Am J Cardiovasc Drugs. 2017 Jun;17(3):235-242. doi: 10.1007/s40256-016-0210-3.