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RecruitingNCT03024008Updated Dec 10, 2025

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

A Phase 1/2 interventional study of BonoFill-II in Bone Fracture, sponsored by BonusBio Group Ltd. Recruiting at 6 sites in Israel. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2025-12-10.

Sponsored by BonusBio Group Ltd · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
40
Allocation
Not applicable
Ages
18 Years to 80 Years
Sex
All
01

Study 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
Read the 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.
02

Conditions studied

  • Bone Fracture

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Keywords

  • Critical Gap
  • Comminuted Fracture
  • Extra-Articular
03

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
40 participants (estimated)

Study arms

  • Experimental
    Intervention Arm

    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

    Biological: BonoFill-II

Interventions

  • BiologicalBonoFill-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.

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Throughout the post-intervention 12-month follow-up

  2. 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.

    Time frame: Starting 4-week follow-up and through to the end of the 12-month follow-up

  3. 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).

    Time frame: The test is performed at 3, 6 and 12 months post operation.

Other outcomes

  1. 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).

    Time frame: 3, 6 and 12 months

06

Study locations

6 of 6 sites recruiting
  • Emek Medical Center
    Afula, 1834111, Israel
    Recruiting
  • Barzilai Medical Center
    Ashkelon, 7830604, Israel
    Recruiting
  • Hillel Yafe
    Hadera, Israel
    Recruiting
  • Carmel Medical Center
    Haifa, Israel
    Recruiting
  • Rambam Health Campus
    Haifa, Israel
    • Doron Norman, MD, PhD · Contact · d_norman@rmc.gov.il
    • Doron Norman, MD, PhD · Principal investigator
    Recruiting
  • Meir Medical Center
    Kfar Saba, Israel
    • Nissim Ohana, MD · Contact · ohanan@clalit.org.il · 972-9-7472502
    • Nissim Ohana, MD · Principal investigator
    Recruiting
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03024008
Lead sponsor
BonusBio Group Ltd
Responsible party
Sponsor
First posted
Jan 18, 2017
Start date
Jul 27, 2017
Primary completion
Mar 2027 (estimated)
Completion
Jun 2027 (estimated)
Last update
Dec 10, 2025

Study contacts

Nimrod Rozen, MD, PhD
Contact
nimrod_rozen@hotmail.com
+972-4-649-4201
Vered Kivity, PhD, MBA
Contact
veredki@bonus-bio.com
+972-73-206-7103
Nimrod Rozen, MD, PhD
principal investigator · Emek Medical Center, Afula, Israel

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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