Gene-activated Matrix for Bone Tissue Repair in Maxillofacial Surgery

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate safety and efficacy of gene-activated matrix (Nucleostim) for regeneration of bone tissue in maxillofacial area. Patients with congenital and acquired maxillofacial defects (sockets of extracted teeth, bone defects after injuries, surgeries, excision of benign neoplasms and pseudotumors, etc.) or alveolar bone atrophy will be included into the study.

Detailed Description
-----------------
All patients enrolled into the study will receive standard surgery procedures indicated in accordance with medical care standards for the certain disease. Maxillofacial bone defects (formed after injuries, surgeries, excision of benign neoplasms and pseudotumors, teeth extraction, etc.) or areas of alveolar bone atrophy will be the filled by gene-activated matrix Nucleostim. Safety and efficacy of implanted osteoplastic material will be assessed by physical examination, comprehensive laboratory tests, X-ray examination within 60 days after operation.

Official Title
-----------------
Clinical Trial of Safety and Efficacy of the Medical Item Collagen Plates With Hydroxyapol Inducing Angiogenesis, Nukleostim, for Bone Tissue Regeneration

Conditions
-----------------
Maxillofacial Bone Defects, Alveolar Bone Atrophy, Jaw Fractures, Maxillofacial Bone Deformities, Bone Neoplasm, Benign, Disorders of Teeth and Jaw

Intervention / Treatment
-----------------
* Device: Gene-activated matrix Nucleostim


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: obtained voluntary informed consent for participation in the clinical study; congenital and acquired maxillofacial bone defects (sockets of extracted teeth, bone defects after injuries, surgeries, excision of benign neoplasms and pseudotumors, etc.) or alveolar bone atrophy. Exclusion Criteria: 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 consumption within 4 days prior the study; history of 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 lactation.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gene-activated matrix Nucleostim<br>Implantation of gene-activated matrix Nucleostim into the bone defects or sites of bone atrophy | Device: Gene-activated matrix Nucleostim<br>* Gene-activated matrix Nucleostim is bone graft substitute consisting of collagen-hydroxyapatite composite scaffold and DNA plasmids with gene encoding vascular endothelial grothw factor (VEGF-A165) in concentration 100-120 ng/mg which is an active substance of gene-therapeutic drug Neovasculgen®.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantity of newly-formed bone tissue in the field of gene-activated matrix implantation | To determine the quantity of newly-formed bone tissue the morphometric parameters of regenerate will be measured on CT scan using special tools (ROI, region of interest, etc.) The morphometric parameters of bone regenerate include: average density (in HU); size (length, width, height) and volume. | 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain scores on the visual analog scale |  | 60 days | 
| Surgical failure rate |  | 60 days | 
| Adverse Events |  | 60 days | 
| Edema scores on the 0-10 Numeric Rating Scale | Level of edema at the surgical site will be assessed by physician using 0-10 Numeric Rating Scale. | 60 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
maxillofacial bone defects, alveolar ridge atrophy, gene-activated matrix, VEGF gene, DNA plasmid, bone gene therapy