Filling Bone Defects/Voids With Autologous BonoFill-II for Maxillofacial Bone Regeneration

Phase I/II Open Label First in Human Single Center Clinical Study Aimed to Evaluate the Safety and Efficacy of BonoFill-II in Reconstructing Maxillofacial Bone

The purpose of this clinical study is to evaluate the safety and the efficacy of BonoFill-II as a bone filler containing the patient's own (autologous) adipose (fat) tissue-derived cells in reconstructing bone in two clinical indications:

1. Bone augmentation (e.g. sinus augmentation)
2. Bone grafting after removal of cysts from jaws

Study Overview

• Status: Recruiting
• Conditions: Bone Augmentation; Bone Grafts
• Intervention / Treatment: Biological: BonoFill-II

Detailed Description

Primary endpoint:

The transplantation of BonoFill-II to the maxillary or mandible defect/void is safe under the following conditions: No chronic bone infection (Osteomyelitis); no significant changes in complete blood count (CBC) and in general health.

Secondary endpoint:

The transplantation of BonoFill-II to the maxillary or mandible void is efficient under the following conditions: Following BonoFill-II implantation, the bone regeneration in the operated site was significantly accelerated. Also, the bone defects/voids were filled with a significant amount of bone tissue.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ephraim Tzur, DMD; Phone Number: 972-53-734-5356; Email: drefitzur@gmail.com

Study Locations

• Israel
  • Kfar Saba, Israel
    • Recruiting
    • Oral and Maxillofacial Surgery Clinic - Beit Merik
    • Contact: Sahar Tzur; Phone Number: 972-50-7891113; Email: moonstruck6@gmail.com
    • Sub-Investigator: Alex Levenberg, MD
    • Sub-Investigator: Shlomo Bulvik, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

GENERAL

1. Subject in general good health in the opinion of the investigator as determined by medical history, vital signs physical examination and safety lab tests
2. Subject has a rehabilitation dentist and rehabilitation program
3. Up to date panoramic X-Ray/CT
4. Subject has provided written informed consent to participate in the study, understands all study procedures and agrees to follow up procedures
5. Subject is in good oral hygiene condition as per investigator's discretion

SINUS AUGMENTATION

1. The subjects requires sinus augmentation as per investigator's discretion
2. Healthy condition of Maxillary Sinuses and Oral Mucosa determined by X-ray

BONE GRAFTING AFTER REMOVAL OF CYSTS FROM JAWS

1. Subject who according to investigator diagnosis required removal of cysts from jaws. Limited to cysts diagnosed as: radicular cysts, residual cysts, congenital cysts, developmental and acquired cysts.
2. Subject's cyst was removed after diagnosis of the cyst type

Exclusion Criteria:

1. Subject with a recorded medical history of diseases such as diabetes mellitus, heart diseases, renal failure, osteoporosis, Multiple sclerosis,
2. Subject treated with systemic steroids
3. Subject with a known autoimmune disease, such as Addison's disease, Myasthenia gravis, Pernicious anemia, Reactive arthritis, Rheumatoid arthritis, Sjogren syndrome, Systemic lupus erythematosus, Type I diabetes.
4. Subject has vitiligo or a known scar healing problems (keloid formation)
5. Subject treated with Oral Bisphosphonate drugs (such as Fosalan and other similar medications)
6. Subjects underwent one of the following treatments up to 12 months prior to Visit 1: Chemotherapy, Radiotherqapy
7. In case of sinus augmentation - unhealthy conditions of Maxillary Sinuses.
8. Subject with current active infection or illness.
9. Subject participating in another clinical trial 30 days prior to and during the study period.
10. Subject is a pregnant or lactating woman. Pregnancy will be verified by urine test during screening.
11. Subject has a known history of any significant medical disorder, which in the investigator's discretion contraindicates the subject's participation.
12. Subject has a known allergy for anesthesia.
13. Subjects with known allergy to hyaluronic acid.
14. Subjects with known allergy to HypoThermosol® or Dextran-40.
15. Subjects with known allergy to any of the antibiotics: Bacitracin, Gentamicin and/or Polymyxin B Sulfate.
16. Positive serology for either HIV, hepatitis B or hepatitis C.
17. Abnormal clinically significant laboratory test and exams findings as per investigator's discretion.

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; 1 Arm - IMP treatment arm

Biological: BonoFill-II; Sinus augmentation - Surgery will be performed by either open or close sinus augmentation as per investigator discretion and as per common medical practice. After the elevation, BonoFill-II will be transplanted on the residual sub-antral bone. Bone grafting after removal of cysts from jaws - Treatment will be performed according to the size of the cyst: in relatively small cyst total enucleation will be performed. In large cysts, a process of marsupialization will be performed. The entire cyst will be removed, including the epithelium layer, and the BonoFill-II product will be used for filling.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Bonofill-ll Administration	The study will assess the safety of the BonoFill-II drug product post transplantation by demonstrating no treatment-related adverse events such as chronic bone infection (Osteomyelitis) or significant changes in complete blood counts. adverse events will be assessed by type, severity, seriousness, relatedness, incidence, and duration.	6-month clinical Follow Up
Efficacy of Bonofill-ll Administration	Following BonoFill-II transplantation, the bone regeneration in the operated site will be evaluated using CT or panoramic X Ray. Bone formation at the implantation site inside the maxillary sinus will be evaluated by measuring the bone height (mm) at the end of the study (residual + Augmented bone at 3 evenly-spaced locations) and comparing to measurements of bone height of the residual bone only prior to Bonofill-ll administration. Efficacy will be evaluated also by having a stable dental implants at the uncovering procedure by the end of the study.	6-month clinical Follow Up

Collaborators and Investigators

• Sponsor: BonusBio Group Ltd
• Investigators: Study Director: Vered Kivity, PhD, MBA, Bonus BioGroup

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2016
• Primary Completion (Anticipated): June 30, 2022
• Study Completion (Anticipated): December 30, 2022

Study Registration Dates

• First Submitted: November 24, 2015
• First Submitted That Met QC Criteria: July 20, 2016
• First Posted (Estimate): July 25, 2016

Study Record Updates

• Last Update Posted (Actual): July 2, 2021
• Last Update Submitted That Met QC Criteria: June 30, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: CP-BNS03

Plan for Individual participant data (IPD)

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