Safety and Efficacy Study of Gene Therapy Drug (Neovasculgen) to Treat Secondary Raynaud's Phenomenon

Study Overview
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Brief Summary
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The purpose of this study is to determine whether pl-vegf165 (Neovasculgen) is effective in the treatment of digital ulcers related to secondary Raynaud's phenomenon associated with systemic scleroderma

Detailed Description
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This is a randomized, open, comparing clinical trial assessing the therapeutic efficacy of pl-vegf165 (Neovasculgen) in treating scleroderma-associated Raynaud's syndrome. Each patient of clinical group will undergo several intramuscular injections with a treatment dose of pl-vegf165 (Neovasculgen) in hand where digital ulcers locate. In the control group patients will receive only standard of care without gene therapy drug. Study participants at the first study visit will complete study questionnaires, their hands will be assessed clinically for digital ulceration, and their hands will undergo non-invasive capillaroscopy. After this initial assessment, the patients of clinical group will undergo intramuscular injections of pl-vegf165 (Neovasculgen) in a hand altered with digital ulcers. Patient will report the severity of their Raynaud's symptoms weekly over the six month study period. At three month post-injection, the patient will complete study questionnaires, their hands will be assessed clinically for digital ulceration, and their hands will undergo non-invasive capillaroscopy. At six months post-injection, the patient will again complete study questionnaires, their hands will be assessed clinically for digital ulceration, and their hands will undergo non-invasive capillaroscopy.

Official Title
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Safety and Efficacy Study of Pl-vegf165 to Treat Secondary Raynaud's Phenomenon Caused by Systemic Scleroderma

Conditions
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Secondary Raynaud's Phenomenon

Intervention / Treatment
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* Drug: Neovasculgen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: obtained voluntary informed consent for participation in the clinical study presence of systemic scleroderma features satisfied to criteria of American College of Rheumatology classification presence at least one active digital ulcer at baseline Exclusion Criteria: presence of another systemic connective tissue disease; absence at least one active digital ulcer at baseline; smoking within 3 months or smoking cessation using nicotine products; subjects currently taking sildenafil, tadalafil or vardenafil; history of sympathectomy over previous 12 months not able or unwilling to give voluntary informed consent for the study or follow requirements of the clinical study; decompensated chronic visceral diseases; clinically significant laboratory abnormalities; HIV, HBV and HCV antibodies in serum; alcohol or drug addiction; participation in other clinical studies (or administration of study products) within 3 months prior the study; conditions limiting study compliance (dementia, psycho-neurological diseases, drug addiction, alcoholism, etc.); malignancies including post-surgical period with chemo- and (or) radiation therapy); vascular malformations; pregnancy or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: pl-vegf165<br>Patients of this group will receive 2,4 mg of pl-vegf165 administered by intramuscular injection which is given in the hand | Drug: Neovasculgen<br>* Neovasculgen is an original gene construction that contains supercoiled plasmid DNA (1.2 mg) that encodes pCMV-vegf165 as the active substance. The drug will be supplied to the study centre as a sterile lyophilisate that will be then dissolved in 2 ml of water for injections immediately prior to administration. The drug will be administered intramuscularly (interosseous muscles of hand) at 4-5 injection sites in the dorsal surface of the hand.<br>|
| No Intervention: standard care<br>Patients of this group will receive standard therapy accepted in a clinical centre | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of new digital ulcers | To determine the ability of pl-vegf165 to prevent development of new digital ulcers the frequency of new digital ulcers will be measured in both groups and then compared | 180 days | 
| Frequency of adverse events |  | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of complete healing of digital ulcers | The ability of pl-vegf165 to accelerate the healing of the digital ulcer will be measured by estimating the area of the defect in progress | 180 days | 
| Pain scores on the visual analog scale | Visual analog scale is a diagnostic tool providing an assessment of the severity and quality of pain experienced by patients. | 180 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gene therapy, plasmid, vegf, systemic scleroderma,secondary raynaud's phenomenon