<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03024008</url>
  </required_header>
  <id_info>
    <org_study_id>CP-BNS05</org_study_id>
    <nct_id>NCT03024008</nct_id>
  </id_info>
  <brief_title>Enhancement of Bone Regeneration and Healing in the Extremities by the Use of Autologous BonoFill-II</brief_title>
  <official_title>A Multicenter Study to Evaluate the Enhancement of Bone Regeneration and Healing in the Extremities by the Use of Autologous BonoFill-II</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BonusBio Group Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>BonusBio Group Ltd</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this clinical study is to evaluate the safety and the efficacy of BonoFill-II&#xD;
      as an autologous bone-regenerating graft in the reconstruction of deficient bone in two&#xD;
      clinical indications:&#xD;
&#xD;
        1. Long and short bone extra-articular comminuted fracture&#xD;
&#xD;
        2. Long and short bones extra and intra articular defect /Gap or non-union, incapable of&#xD;
           self-regeneration&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Endpoint:&#xD;
&#xD;
      Safety: to establish that the transplantation of BonoFill-II into bone defect/gap is safe&#xD;
      under the following conditions:&#xD;
&#xD;
        -  No treatment-related appearance of heterotrophic bone ossification&#xD;
&#xD;
        -  No excessive bone formation at the transplantation sites&#xD;
&#xD;
        -  No abnormalities in the treated sites&#xD;
&#xD;
      Efficacy: to establish that the transplantation of BonoFill-II into bone defect/gap is&#xD;
      effective under the following conditions:&#xD;
&#xD;
      Bone continuity rate, measured radiographically by CT at 6 and 12 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 27, 2017</start_date>
  <completion_date type="Anticipated">September 2022</completion_date>
  <primary_completion_date type="Anticipated">June 2022</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of subjects with treatment-emergent appearance of safety issues</measure>
    <time_frame>Throughout the post-intervention 12-month follow-up</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Bone continuity</measure>
    <time_frame>Starting 4-week follow-up and through to the end of the 12-month follow-up</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to union</measure>
    <time_frame>Starting 4-week follow-up and through to the end of the 12-month follow-up</time_frame>
    <description>Time to bone union will be recorded. Outcome measure will be reported in months and weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weight bearing ability</measure>
    <time_frame>3, 6 and 12 months</time_frame>
    <description>clinical examination of weight bearing ability for lower extremities or coffee-cup weight bearing ability for upper extremities</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lack of pain at the surgical site</measure>
    <time_frame>3, 6 and 12 months</time_frame>
    <description>Clinical evaluated by movements of the joints above and below the surgical site area</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Bone Fracture</condition>
  <arm_group>
    <arm_group_label>Intervention Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Clinical Interventions:&#xD;
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.&#xD;
Xray&#xD;
Urine Test&#xD;
CT&#xD;
Liposuction - harvest of 50-300ml autologous adipose tissue from the subject's abdomen&#xD;
Single transplantation of Investigational Medicinal Product BonoFill-II into long bone extra-articular comminuted fracture or large bone defect/critical gap</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>BonoFill-II</intervention_name>
    <description>Surgery will be performed under local or general anesthetics according to the Investigator's and anesthesiologist discretion.&#xD;
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.&#xD;
internal fixation (plate and screws and intramedullary nails) will not be routinely removed. External fixators will be removed upon achievement of satisfactory bone union.</description>
    <arm_group_label>Intervention Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Long and short bones extra articular comminuted fracture or&#xD;
&#xD;
          -  Long and short bones extra and intra articular defect/gap or non union, incapable of&#xD;
             self-regeneration&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age is under 18 or above 80&#xD;
&#xD;
          -  A simple fracture manageable by one definitive treatment&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Patients with active infection anywhere in the body except in the injured bone site&#xD;
             that is in question and needs osteogenic treatment.&#xD;
&#xD;
          -  Subjects with recorded medical history diseases such as heart diseases, renal failure.&#xD;
&#xD;
          -  Subject treated currently with systemic steroids.&#xD;
&#xD;
          -  Subjects with known autoimmune diseases, such as Addison's disease, Celiac disease -&#xD;
             sprue (gluten-sensitive enteropathy), Dermatomyositis, Graves disease, Hashimoto's&#xD;
             thyroiditis, Multiple sclerosis, Myasthenia gravis, Pernicious anemia, Reactive&#xD;
             arthritis, Rheumatoid arthritis, Sjogren syndrome, Systemic lupus erythematosus.&#xD;
&#xD;
          -  Subjects diagnosed with osteoporosis&#xD;
&#xD;
          -  Subjects that have a known scar healing problem (keloid formation).&#xD;
&#xD;
          -  Subjects treated with Bisphosphonate drugs&#xD;
&#xD;
          -  Oncology patients in treatment&#xD;
&#xD;
          -  Subjects who received chemotherapy or radiotherapy treatment in the past&#xD;
&#xD;
          -  Subjects participating in another clinical trial 30 days prior to and during the study&#xD;
             period.&#xD;
&#xD;
          -  Drug addicts and psychiatric patients patients incapable of giving consent.&#xD;
&#xD;
          -  Subjects with a known history of any significant medical disorder, which in the&#xD;
             investigator's judgment contraindicates the subject's participation.&#xD;
&#xD;
          -  Subjects with any known allergy for local/general anesthesia.&#xD;
&#xD;
          -  Positive serology for either HIV, hepatitis B or hepatitis C.&#xD;
&#xD;
          -  Abnormal clinically significant laboratory test and findings, as per the&#xD;
             investigator's judgment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nimrod Rozen, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emek Medical Center, Afula, Israel</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Nimrod Rozen, MD, PhD</last_name>
    <phone>+972-4-649-4201</phone>
    <email>nimrod_rozen@hotmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Vered Kivity, PhD, MBA</last_name>
    <phone>+972-73-206-7103</phone>
    <email>veredki@bonus-bio.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Emek Medical Center</name>
      <address>
        <city>'Afula</city>
        <zip>1834111</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nimrod Rozen, MD, PhD</last_name>
      <phone>04-6494201</phone>
      <email>nimrod_rozen@hotmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hillel Yafe</name>
      <address>
        <city>Hadera</city>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yaniv Yonay, MD</last_name>
      <phone>972-4-7744738</phone>
      <email>yanivy@hy.health.gov.il</email>
    </contact>
    <investigator>
      <last_name>Yaniv Yonay, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Carmel Medical Center</name>
      <address>
        <city>Haifa</city>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Benny Bernfeld, MD</last_name>
      <phone>972-4-8250506</phone>
      <email>bernfeld_benny@clalit.org.il</email>
    </contact>
    <investigator>
      <last_name>Benny Bernfeld, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Rambam Health Campus</name>
      <address>
        <city>Haifa</city>
        <country>Israel</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Doron Norman, MD, PhD</last_name>
      <email>d_norman@rmc.gov.il</email>
    </contact>
    <investigator>
      <last_name>Doron Norman, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Meir Medical Center</name>
      <address>
        <city>Kfar Saba</city>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nissim Ohana, MD</last_name>
      <phone>972-9-7472502</phone>
      <email>ohanan@clalit.org.il</email>
    </contact>
    <investigator>
      <last_name>Nissim Ohana, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>January 11, 2017</study_first_submitted>
  <study_first_submitted_qc>January 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 18, 2017</study_first_posted>
  <last_update_submitted>June 30, 2021</last_update_submitted>
  <last_update_submitted_qc>June 30, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Critical Gap</keyword>
  <keyword>Comminuted Fracture</keyword>
  <keyword>Extra-Articular</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fractures, Bone</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03024008
org study id: CP-BNS05
nct id: NCT03024008
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of subjects with treatment-emergent appearance of safety issues
time frame: Throughout the post-intervention 12-month follow-up
description: 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.
measure: Bone continuity
time frame: Starting 4-week follow-up and through to the end of the 12-month follow-up
description: 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.
measure: Time to union
time frame: Starting 4-week follow-up and through to the end of the 12-month follow-up
description: Time to bone union will be recorded. Outcome measure will be reported in months and weeks.
measure: Weight bearing ability
time frame: 3, 6 and 12 months
description: clinical examination of weight bearing ability for lower extremities or coffee-cup weight bearing ability for upper extremities
measure: Lack of pain at the surgical site
time frame: 3, 6 and 12 months
description: Clinical evaluated by movements of the joints above and below the surgical site area
arm group label: Intervention Arm
arm group type: Experimental
description: 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
intervention type: Biological
intervention name: BonoFill-II
description: 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.
arm group label: Intervention Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Nimrod Rozen, MD, PhD
role: Principal Investigator
affiliation: Emek Medical Center, Afula, Israel
last name: Nimrod Rozen, MD, PhD
phone: +972-4-649-4201
email: nimrod_rozen@hotmail.com
last name: Vered Kivity, PhD, MBA
phone: +972-73-206-7103
email: veredki@bonus-bio.com
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Israel
responsible party type: Sponsor
mesh term: Fractures, Bone
sharing ipd: No