Clinical trial NCT03076138: Gene-activated Bone Substitute for Maxillofacial Bone Regeneration
Official title: The Clinical Trial of the Safety and Efficacy of the Medical Device "Bone Substitute Based on Octacalcium Phosphate and Biologically Active Nucleic Acids for Bone Tissue Regeneration" (Nucleostim-VEGF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Bone Cysts
Bone Atrophy
Bone Deformity
Bone Fracture
Bone Loss
Tooth Loss
Keywords: Gene-activated matrix
Bone substitute
Bone grafting
Dental implantation
gene therapy
plasmid DNA
VEGF gene
octacalcium phosphate
Lead sponsor: Histograft Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Moscow State University of Medicine and Dentistry
First posted: 2017-03-10
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and efficacy of the gene-activated bone substitute consisting of octacalcium phosphate and plasmid DNA encoding vascular endothelial growth factor (VEGF) for maxillofacial bone regeneration. The patients with congenital and acquired maxillofacial bone defects and alveolar ridge atrophy will be enrolled.

Detailed description: All participants of the study will receive standard treatment according to the medical care standards for diseases and pathological conditions characterized by maxillofacial bone defects and/or alveolar ridge atrophy. Bone grafting procedures as part of the surgical treatment will be performed with the use of investigated medical device. The safety and efficacy of the implanted gene-activated bone substitute will be evaluated by clinical examination, comprehensive laboratory tests, and computer tomography within 6 months after surgery.

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, removal of benign neoplasms and pseudotumors, etc.) or alveolar ridge 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 trials (or administration of study products) within 3 months prior the study;
* conditions limiting study compliance (dementia, psycho-neurological diseases, drug addiction, alcoholism, etc.);
* pregnancy or lactation;
* malignancies including post-treatment period (surgical, chemotherapy, radiation therapy both alone and in different combinations) less than 5 years prior the study.

Primary outcomes:
measure: Bone tissue formation in the field of gene-activated bone substitute implantation
timeFrame: 6 months
Secondary outcomes:
measure: Adverse Events and Serious Adverse Events
timeFrame: 6 months
measure: Surgical failure rate
timeFrame: 6 months
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: A.I. Moscow State University of Medicine and Dentistry
Study officials:
affiliation: A.I. Evdokimov Moscow State University of Medicine and Dentistry
name: Alexey Y. Drobyshev, MD,PhD,Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Deev RV, Drobyshev AY, Bozo IY, Isaev AA. Ordinary and Activated Bone Grafts: Applied Classification and the Main Features. Biomed Res Int. 2015;2015:365050. doi: 10.1155/2015/365050. Epub 2015 Nov 15.
citation: Komlev VS, Barinov SM, Bozo II, Deev RV, Eremin II, Fedotov AY, Gurin AN, Khromova NV, Kopnin PB, Kuvshinova EA, Mamonov VE, Rybko VA, Sergeeva NS, Teterina AY, Zorin VL. Bioceramics composed of octacalcium phosphate demonstrate enhanced biological behavior. ACS Appl Mater Interfaces. 2014 Oct 8;6(19):16610-20. doi: 10.1021/am502583p. Epub 2014 Sep 16.
citation: Komlev VS, Popov VK, Mironov AV, Fedotov AY, Teterina AY, Smirnov IV, Bozo IY, Rybko VA, Deev RV. 3D Printing of Octacalcium Phosphate Bone Substitutes. Front Bioeng Biotechnol. 2015 Jun 8;3:81. doi: 10.3389/fbioe.2015.00081. eCollection 2015.
citation: Deev R, Plaksa I, Bozo I, Isaev A. Results of an International Postmarketing Surveillance Study of pl-VEGF165 Safety and Efficacy in 210 Patients with Peripheral Arterial Disease. Am J Cardiovasc Drugs. 2017 Jun;17(3):235-242. doi: 10.1007/s40256-016-0210-3.
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.