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

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

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

Study Overview

• Status: Recruiting
• Conditions: Bone Fracture
• Intervention / Treatment: Biological: BonoFill-II

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, measured radiographically by CT at 6 and 12 months.
• Weight-bearing ability, assessed at 6 and 12 months.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Nimrod Rozen, MD, PhD; Phone Number: +972-4-649-4201; Email: nimrod_rozen@hotmail.com
• Study Contact Backup: Name: Vered Kivity, PhD, MBA; Phone Number: +972-73-206-7103; Email: veredki@bonus-bio.com

Study Locations

• Israel
  • Afula, Israel, 1834111
    • Recruiting
    • Emek Medical Center
    • Contact: Nimrod Rozen, MD, PhD; Phone Number: 04-6494201; Email: nimrod_rozen@hotmail.com
  • Ashkelon, Israel, 7830604
    • Recruiting
    • Barzilai Medical Center
    • Contact: Omri Lubovski, MD; Phone Number: 972-8-6745034; Email: omril@bmc.gov.il
  • Hadera, Israel
    • Recruiting
    • Hillel Yafe
    • Contact: Yaniv Yonay, MD; Phone Number: 972-4-7744738; Email: yanivy@hy.health.gov.il
    • Principal Investigator: Yaniv Yonay, MD
  • Haifa, Israel
    • Recruiting
    • Carmel Medical Center
    • Contact: Benny Bernfeld, MD; Phone Number: 972-4-8250506; Email: bernfeld_benny@clalit.org.il
    • Principal Investigator: Benny Bernfeld, MD
  • Haifa, Israel
    • Recruiting
    • Rambam Health Campus
    • Contact: Doron Norman, MD, PhD; Email: d_norman@rmc.gov.il
    • Principal Investigator: Doron Norman, MD, PhD
  • Kfar Saba, Israel
    • Recruiting
    • Meir Medical Center
    • Contact: Nissim Ohana, MD; Phone Number: 972-9-7472502; Email: ohanan@clalit.org.il
    • Principal Investigator: Nissim Ohana, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 that is in question and needs osteogenic treatment.
• More than 3 previous failed interventions at the surgical site
• History of advanced congestive heart failure or active acute myocardial infarction (AMI), renal failure (estimated GFR of <30 ml/min/1.73 m2 at screening), or hepatic disease (hepatic insufficiency classified as Child-Pugh B or C)
• Diabetic subjects (HbA1c > 8)
• 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
• Chronic severe PVD (Peripheral Vascular Disease) subjects
• Post major vascular operation in the treated limb/s and above the surgical site (with or without Gore-Tex grafting)
• Subjects that have a known scar healing problem (keloid formation).
• Subjects treated with Bisphosphonate drugs
• Oncology patient or subjects who received chemotherapy or radiotherapy treatment in the past 12 months
• Immunocompromised condition from any reason, at screening
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intervention Arm; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary safety endpoint: Absence of treatment-emergent appearance of safety issues	Subjects demonstrating no 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 X-ray and/or CT.	Throughout the post-intervention 12-month follow-up
Efficacy endpoint: Bone continuity	Bone union, as assessed by X-ray and CT. CT scans are performed 6 and 12 months post operation, to verify bone regeneration and complete bone continuity was achieved.	Starting 4-week follow-up and through to the end of the 12-month follow-up
Functional efficacy endpoint: Weight bearing ability	clinical examination of weight bearing ability for lower extremities or coffee-cup weight bearing ability for upper extremities. The physician assesses the functionality of the operated limb, by testing the patients ability to bear their weight when standing (in case of lower limb bone defect) or by coffee cup holding simulation (in case of upper limb bone defect).	The test is performed at 3, 6 and 12 months post operation.

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lack of pain at the surgical site	Pain at the surgical site will be evaluated using a VAS pain scale, this assessment will be used in cases of bone defect where weight-bearing is not applicable due to further limb injuries (such as nerve injuries or other non-bone defects).	3, 6 and 12 months

Collaborators and Investigators

• Sponsor: BonusBio Group Ltd
• Investigators: Principal Investigator: Nimrod Rozen, MD, PhD, Emek Medical Center, Afula, Israel

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2017
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: January 11, 2017
• First Submitted That Met QC Criteria: January 15, 2017
• First Posted (Estimated): January 18, 2017

Study Record Updates

• Last Update Posted (Estimated): December 10, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Critical Gap; Comminuted Fracture; Extra-Articular
• Additional Relevant MeSH Terms: Wounds and Injuries; Fractures, Bone; Fractures, Comminuted
• Other Study ID Numbers: CP-BNS05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No