Enhancement of Bone Regeneration and Healing in the Extremities by the Use of Autologous BonoFill-II

Study Overview
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Brief Summary
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The purpose of this clinical study is to evaluate the safety and the efficacy of BonoFill-II as an autologous bone-regenerating graft in the reconstruction of deficient bone in two clinical indications: Long and short bone extra-articular comminuted fracture Long and short bones extra and intra articular defect /Gap or non-union, incapable of self-regeneration

Detailed Description
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Primary Endpoint: Safety: to establish that the transplantation of BonoFill-II into bone defect/gap is safe under the following conditions: No treatment-related appearance of heterotrophic bone ossification No excessive bone formation at the transplantation sites No abnormalities in the treated sites Efficacy: to establish that the transplantation of BonoFill-II into bone defect/gap is effective under the following conditions: Bone continuity rate, measured radiographically by CT at 6 and 12 months.

Official Title
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A Multicenter Study to Evaluate the Enhancement of Bone Regeneration and Healing in the Extremities by the Use of Autologous BonoFill-II

Conditions
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Bone Fracture

Intervention / Treatment
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* Biological: BonoFill-II


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Long and short bones extra articular comminuted fracture or Long and short bones extra and intra articular defect/gap or non union, incapable of self-regeneration Exclusion Criteria: Age is under 18 or above 80 A simple fracture manageable by one definitive treatment Pregnant or lactating women Patients with active infection anywhere in the body except in the injured bone site that is in question and needs osteogenic treatment. Subjects with recorded medical history diseases such as heart diseases, renal failure. Subject treated currently with systemic steroids. Subjects with known autoimmune diseases, such as Addison's disease, Celiac disease - sprue (gluten-sensitive enteropathy), Dermatomyositis, Graves disease, Hashimoto's thyroiditis, Multiple sclerosis, Myasthenia gravis, Pernicious anemia, Reactive arthritis, Rheumatoid arthritis, Sjogren syndrome, Systemic lupus erythematosus. Subjects diagnosed with osteoporosis Subjects that have a known scar healing problem (keloid formation). Subjects treated with Bisphosphonate drugs Oncology patients in treatment Subjects who received chemotherapy or radiotherapy treatment in the past Subjects participating in another clinical trial 30 days prior to and during the study period. Drug addicts and psychiatric patients patients incapable of giving consent. Subjects with a known history of any significant medical disorder, which in the investigator's judgment contraindicates the subject's participation. Subjects with any known allergy for local/general anesthesia. Positive serology for either HIV, hepatitis B or hepatitis C. Abnormal clinically significant laboratory test and findings, as per the investigator's judgment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Arm<br>Clinical Interventions: Blood tests: complete blood count, full blood chemistry and biochemistry including phosphate, alkaline phosphatase, calcium, renal and liver function, and coagulation. Serology tests: HIV, Hepatitis B, Hepatitis C. Xray Urine Test CT Liposuction - harvest of 50-300ml autologous adipose tissue from the subject's abdomen Single transplantation of Investigational Medicinal Product BonoFill-II into long bone extra-articular comminuted fracture or large bone defect/critical gap | Biological: BonoFill-II<br>* Surgery will be performed under local or general anesthetics according to the Investigator's and anesthesiologist discretion. A standard orthopedic approach will be made according to the fracture site.Then the transplantation of BonoFill-II into the fracture site and the fixation of the fracture by intramedullary nail or plate and screws or external fixator as required will be performed. internal fixation (plate and screws and intramedullary nails) will not be routinely removed. External fixators will be removed upon achievement of satisfactory bone union.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with treatment-emergent appearance of safety issues | Subjects will be followed-up for appearance of heterotrophic bone ossification, excessive bone formation and/or any abnormalities in the treated site, in the proximal or distal joint by visual examination of the transplantation site and by Xray. Outcome measure will be reported in number of incidences. Results will be aggregated into one single value of each one of the safety issues, indicating the number of subjects displaying these treatment-related safety issues. | Throughout the post-intervention 12-month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone continuity | Bone union will be assessed by Xray and confirmed by CT. Outcome measure will be reported by Results will be aggregated into one single value indicating the number of subjects displaying bone union/continuity. | Starting 4-week follow-up and through to the end of the 12-month follow-up | 
| Time to union | Time to bone union will be recorded. Outcome measure will be reported in months and weeks. | Starting 4-week follow-up and through to the end of the 12-month follow-up | 
| Weight bearing ability | clinical examination of weight bearing ability for lower extremities or coffee-cup weight bearing ability for upper extremities | 3, 6 and 12 months | 
| Lack of pain at the surgical site | Clinical evaluated by movements of the joints above and below the surgical site area | 3, 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Critical Gap, Comminuted Fracture, Extra-Articular