The Endovascular Plus GENe Therapy Versus Only EndoVascular Therapy for Severe Limb ischaemiA Trial

NCT06473740 | Recruiting Phase 4 DMC

• 1 other identifier: GENEVA
• Study Type: interventional
• Target: 386
• Locations: 1 country
• Sites: 1

Brief Summary

GENEVA is the world's first multicenter, randomized, prospective, controlled trial of the clinical effectiveness of best endovascular treatment versus best endovascular treatment combined with gene therapy for severe lower limb ischemia (Rutherford categories 4 and 5). The researchers hypothesized that the combination treatment would significantly reduce the number of re-interventions on the operated segment and high amputations, and also significantly increase the time interval between re-interventions.

Conditions

Severe Lower Limb Ischemia

Keywords

gene therapy; amputation; severe lower limb ischemia; endovascular treatment; stenting; balloon angioplasty

Outcome Measures

Primary Outcomes (2)

• Numper of participants with freedom from repeated interventions on the operated segment

  the need for re-intervention on the operated segment will be determined based on the clinical data (return of severe ischemia of the operated limb) together with ultrasound and/or computed tomography data; counting the number of re-interventions in the study group

  within 2 years after the intervention

• Numper of participants with freedom from high amputations

  amputations will be performed in patients with the development of gangrene of the lower limb; counting the number of high amputations in each study group

  within 2 years after the intervention

Secondary Outcomes (11)

• amputation-free survival

  within 2 years after the intervention

• overall survival

  within 2 years after the intervention

• time to major amputation

  within 2 years after the intervention

• time to MALE (Major adverse limb event )

  within 2 years after the intervention

• time to MACE (Major adverse cardiovascular event )

  within 2 years after the intervention

Study Arms (2)

Observation group

EXPERIMENTAL

Best endovascular treatment + Introduction Neovasculgen (International nonproprietary or group name: deoxyribonucleic acid plasmid supercoiled pCMV-VEGF165). Dosage form: Lyophilisate for the preparation of a solution for intramuscular administration in the form of a white powder. Composition for 1 bottle: Active ingredient: supercoiled plasmid deoxyribonucleic acid pCMV-VEGF165 1.2 mg. Excipients: dextrose monohydrate - 60.0 mg, sodium hydrogen phosphate dodecahydrate - 3.94 mg, sodium dihydrogen phosphate dihydrate - 0.16 mg. Description: White lyophilisate. Administer 1 bottle diluted in 20-50 ml of saline on days 7 and 21 after endovascular intervention intramuscularly along the affected vessel.

Drug: Deoxyribonucleic acid supercoiled plasmid pCMV-VEGF165 (Neovasculgen)

Standart of Care

NO INTERVENTION

Arterial stenting with stent grafts or balloon angioplasty

Interventions

Deoxyribonucleic acid supercoiled plasmid pCMV-VEGF165 (Neovasculgen) DRUG

The drug "Neovasculgen" is a highly purified supercoiled form of the pCMV-VEGF165 plasmid, encoding the Vascular endothelial growth factor (VEGF) under the control of a promoter (DNA control region). Recombinant plasmid DNA consists of the following components: a fragment of the regulatory region (22 nucleotide pairs), which determines the transcription of the gene, the VEGF minigene, upon expression of which the VEGF isoform is synthesized, consisting of 165 amino acids, a splicing signal, a polyadenylation signal and the SV40 transcription terminator, ensuring the synthesis of the mature RNA gene and auxiliary regions required for efficient biosynthesis of plasmid DNA in the cells of the producer strain of Escherichia coli. When molecules of this plasmid penetrate into mammalian cells, VEGF is produced, which stimulates endothelial cells, which leads to the growth of blood vessels (vascularization) in the area of injection.

Observation group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women 18 years of age and older;
• Atherosclerotic infrainguinal disease of the peripheral arteries (occlusive-stenotic lesion below the inguinal fold);
• Severe ischemia of the lower extremity, characterized by pain at rest or a non-healing ischemic ulcer, which corresponds to Rutherford categories 4-5 and Fontaine grades III-IV;
• Without any previous surgical intervention of the ipsilateral n/a below the inguinal fold;
• Suitable for endovascular treatment according to researchers;
• Adequate inflow through the aorto-iliac segment;
• Willingness to comply with the study protocol, attend follow-up examinations, comply with all instructions and provide written informed consent.
• Infrainguinal disease of peripheral arteries of non-atherosclerotic origin (aortoarteritis, thromboangiitis, congenital anomalies, vascular injuries, etc.) or acute ischemia;
• Severe ischemia of the lower limb, characterized by gangrene (Rutherford category 6);
• The presence of a popliteal aneurysm (\>2.0 cm) on the area of interest;
• Life expectancy \<2 years, for reasons not related to occlusive-stenotic disease of the arteries of the n/c;
• Planned high amputation on the ipsilateral lower extremity within 4 weeks after the planned endovascular procedure;
• Hypersensitivity to any components included in the study drug;
• Previous surgical intervention below the inguinal fold (open vascular, endovascular or hybrid treatment);
• Open treatment of the inflow tract of the ipsilateral lower limb within 6 weeks before enrollment in the study (aortofemoral, iliofemoral, axillofemoral, femorofemoral bypass);

You may not qualify if:

• Refusal of the patient to further participate in the study;
• Use of drugs from the list of prohibited concomitant therapy;
• The use of any other concomitant therapy that, in the opinion of the investigator, may interfere with the assessment of the effectiveness and safety of the investigational medicinal product and/or distort the results of the study;
• Onset of pregnancy;
• Injuries and damage to the ipsilateral lower limb, which, in the opinion of the investigator, may interfere with the assessment of the effectiveness and safety of the study drug and/or distort the results of the study;
• The presence of an adverse event that, in the opinion of the investigator, indicates that continued participation in the study poses an unacceptable risk for the patient.
• The occurrence or identification of concomitant diseases that prevent the patient's further participation in the clinical trial, in the opinion of the investigator.

Sponsors & Collaborators

• Amur State Medical Academy: lead

Study Sites (1)

Amur State Medical Academy

Blagoveshchensk, Amur Oblast, 675001, Russia

RECRUITING

Related Publications (1)

• Vasil'ev AP, Strel'tsova NN, Bessonov IS, Korotkikh AV. [State of microcirculation in patients with atherosclerosis and diabetes mellitus after limb revascularization]. Angiol Sosud Khir. 2020;26(1):22-29. doi: 10.33529/ANGIO2020112. Russian.

  PMID: 32240132 BACKGROUND

Study Officials

• Alrxander Korotkikh, PhD

  Amur State Medical Academy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alrxander Korotkikh, PhD

CONTACT

+7 (922) 079-06-22; dr.alex.korotkikh@gmail.cpm

Sergey Radaev

CONTACT

+70(969) 255-14-30; radaev@nextgene.ru

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 29, 2024
• First Posted: June 25, 2024
• Study Start: June 20, 2024
• Primary Completion (Estimated): May 19, 2027
• Study Completion (Estimated): May 19, 2029
• Last Updated: August 5, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR

Locations

RU (1)