Comparative Study of Gene-activated Bone Substitute and Autobone in Treatment of Long Bone Nonunions

Sponsor

Histograft Co., Ltd. (Industry)

Overall Status

Enrolling by invitation

CT.gov ID

NCT04705857

Collaborator

S. M. Kirov Military Medical Academy of the Ministry of Defense of the Russian Federation (Other)

Enrollment

Location

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study is aimed to compare the effectiveness of "Histograft" bone substitute (gene-activated bone substitute based on octacalcium phosphate and plasmid DNA encoding VEGFA gene) mixed with shredded autobone and pure shredded auto bone harvested from iliac crest in treatment of patients with long bone nonunions

Condition or Disease	Intervention/Treatment	Phase
Non Union Fracture Non-Union of Ankle Joint Without Infection	Combination Product: "Histograft", a bone substitute based on octacalcium phosphate (OCP) and plasmid DNA encoding VEGFA gene

Detailed Description

An open-label randomized controlled clinical trial, two cohorts. Patients who met the inclusion criteria are planned to be enrolled into the trial. Upon enrollment, all patients will undergo screening, a set of clinical examination, instrumental investigations and laboratory tests, including CT of the affected bone with the assessment of nonunion.

All patients enrolled in the study will be subjected to bone reconstructive surgery with nonunion excision and bone grafting with either investigational bone substitute mixed with shredded autobone (in a ratio of 50/50) harvested during the surgery or pure shredded autobone from iliac crest.

The clinical study results will be evaluated at the time points of 1, 15, 45, 90, 180 days with clinical examination, instrumental investigations and laboratory tests. Control CT will be carried out for the primary outcome measure at 90, 180, 360 days after surgery.

Study Design

Study Type:

Observational

Anticipated Enrollment :

20 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Comparative Study of Gene-activated Bone Substitute Based on Octacalcium Phosphate and Plasmid DNA Encoding VEGFA Gene Mixed With Autobone and Bone Autograft From Iliac Crest in Treatment of Long Bone Nonunions With Bone Loss: an Open-label Randomized Controlled Trial

Actual Study Start Date :

Aug 1, 2020

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Sep 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
test group bone reconstructive surgery with the use of "Histograft" bone substitute (gene-activated matrix based on octacalcium phosphate and plasmid DNA encoding VEGFA gene) mixed with shredded autobone (in a ratio of 50/50) harvested during the surgery	Combination Product: "Histograft", a bone substitute based on octacalcium phosphate (OCP) and plasmid DNA encoding VEGFA gene gene-activated bone substitute in granular form, concentration of the plasmid DNA is 100 μg per 1.0 g of the OCP scaffold
control group bone reconstructive surgery with the use of shredded bone autograft harvested from iliac crest

Arm

Intervention/Treatment

test group

bone reconstructive surgery with the use of "Histograft" bone substitute (gene-activated matrix based on octacalcium phosphate and plasmid DNA encoding VEGFA gene) mixed with shredded autobone (in a ratio of 50/50) harvested during the surgery

Combination Product: "Histograft", a bone substitute based on octacalcium phosphate (OCP) and plasmid DNA encoding VEGFA gene

gene-activated bone substitute in granular form, concentration of the plasmid DNA is 100 μg per 1.0 g of the OCP scaffold

control group

bone reconstructive surgery with the use of shredded bone autograft harvested from iliac crest

Outcome Measures

Primary Outcome Measures

Bone consolidation [12 months]
Radiographic assessment of bone healing using REBORNE scale

Secondary Outcome Measures

Adverse Events and Serious Adverse Events [12 months]
Evaluation of the Adverse Events and Serious Adverse Events frequency
Ability to use the operated limb [12 months]
Clinical assessment using DASH scale (for upper limb) or LEFS scale (for lower limb)
Pain level [12 months]
Level of pain measured using Numeric Rating Scale

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Inclusion Criteria:

traumatic isolated closed or open Gustilo I and II, IIIA and IIIB humerus, tibial or femur diaphyseal or metaphysodiaphyseal fracture with a status of atrophic, oligotrophic or normotrophic non-union;
signed voluntary informed consent

Exclusion Criteria:

hypertrophic non-union;
disability or unwillingness to give a voluntary informed consent or follow requirements of the clinical trial;
segmental bone loss requiring specific therapy (bone transport, vascularized graft, large structural allograft, megaprosthesis, etc);
other fractures causing interference with weight bearing;
visceral injuries or diseases interfering with callus formation (severe cranioencephalic trauma, etc.);
unrecovered vascular or neural injury;
infection of any location and aetiology;
pregnancy, breast feeding women and women who are of childbearing age and not practicing adequate birth control;
malignant tumour (past history or concurrent disease);
history of bone harvesting on iliac crest contraindicating new iliac crest bone graft harvesting or bone marrow collection;
conditions limiting study compliance (e.g., dementia, psycho-neurological diseases, drug addiction, and alcoholism);
medication affecting bone turnover (oral bisphosphonates, PTH, sodium fluoride, strontium ranelate, calcitonin, testosterone, systemic cortico- or anabolic steroids)