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

Phase 1

• Conditions: Bone Fracture
• Interventions: Biological: BonoFill-II

• Registration Number: NCT03024008
• Lead Sponsor: BonusBio Group Ltd

Brief Summary

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:

1. Long and short bone extra-articular comminuted fracture

2. Long and short bones extra and intra articular defect /Gap or non-union, incapable of self-regeneration

Detailed Description

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.

Study Timeline

• Study First Submitted: 2017-01-11
• Study First Submitted QC: 2017-01-15
• Study First Posted: 2017-01-18
• Study Start: 2017-07-27
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-30
• Last Update Posted: 2021-07-02
• Primary Completion: 2022-06
• Study Completion: 2022-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intervention Arm	BonoFill-II	Clinical Interventions: 1. 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. 2. Xray 3. Urine Test 4. CT 5. Liposuction - harvest of 50-300ml autologous adipose tissue from the subject's abdomen 6. Single transplantation of Investigational Medicinal Product BonoFill-II into long bone extra-articular comminuted fracture or large bone defect/critical gap

Primary Outcome Measures

Name	Time	Method
Number of subjects with treatment-emergent appearance of safety issues	Throughout the post-intervention 12-month follow-up	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.

Secondary Outcome Measures

Name	Time	Method
Lack of pain at the surgical site	3, 6 and 12 months	Clinical evaluated by movements of the joints above and below the surgical site area
Time to union	Starting 4-week follow-up and through to the end of the 12-month follow-up	Time to bone union will be recorded. Outcome measure will be reported in months and weeks.
Weight bearing ability	3, 6 and 12 months	clinical examination of weight bearing ability for lower extremities or coffee-cup weight bearing ability for upper extremities
Bone continuity	Starting 4-week follow-up and through to the end of the 12-month follow-up	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.

Trial Locations

Locations (5)

Hillel Yafe; 🇮🇱 Hadera, Israel

Emek Medical Center; 🇮🇱 'Afula, Israel

Rambam Health Campus; 🇮🇱 Haifa, Israel

Carmel Medical Center; 🇮🇱 Haifa, Israel

Meir Medical Center; 🇮🇱 Kfar Saba, Israel