<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/NCT03826784</url>
  </required_header>
  <id_info>
    <org_study_id>CAR-BHA-U31</org_study_id>
    <nct_id>NCT03826784</nct_id>
  </id_info>
  <brief_title>Bone Healing Accelerant Versus Standard of Care for Open Tibia Fractures</brief_title>
  <official_title>A Multicenter, Randomized, Controlled, Blinded Study of the Efficacy and Safety of Bone Healing Accelerant Versus Standard of Care in Subjects With Open Tibia Fractures</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Carmell Therapeutics Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Carmell Therapeutics Corporation</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This clinical study is being conducted to demonstrate the safety and effectiveness of the&#xD;
      Bone Healing Accelerant (BHA) product when applied to tibia (leg bone) fractures with an&#xD;
      external wound or skin break (also called open tibia fractures). It is hypothesized that by 6&#xD;
      months, the number of subjects with successful bone healing will be greater in the&#xD;
      BHA-treated group compared to subjects treated with standard of care alone. Open tibia&#xD;
      fractures were chosen for this study because healing rates are typically longer than for&#xD;
      other bone fractures due to the limited vascular supply, limited soft tissue coverage, and&#xD;
      higher risk of infection.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Combined into an international study (CAR-BHA-I21)&#xD;
  </why_stopped>
  <start_date type="Anticipated">November 2019</start_date>
  <completion_date type="Anticipated">February 2022</completion_date>
  <primary_completion_date type="Anticipated">January 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Composite healing measure</measure>
    <time_frame>6 months</time_frame>
    <description>Proportion of subjects in each arm meeting the healing success criteria. A binary (Yes/No) outcome for overall healing will be derived from the following three outcomes: Radiographic healing as measured by a score of at least 13 on the modified Radiographic Union Scale in Tibia fractures (mRUST, range bad to good 1-16), ambulation as measured by a score of at least 2 on the Function IndeX for Trauma scale (range bad to good 0-3), and no secondary intervention to promote bone healing. All three components must be met for a &quot;yes&quot; on composite healing.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Radiographic healing</measure>
    <time_frame>6 months</time_frame>
    <description>Population mean Modified Radiographic Union Scale in Tibia Fractures (mRUST) scores (range bad to good is 4-16)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary intervention (surgical or nonsurgical)</measure>
    <time_frame>6 months</time_frame>
    <description>Proportion of subjects not having secondary intervention conducted specifically to promote bone healing needed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Surgical site infection</measure>
    <time_frame>12 months</time_frame>
    <description>Proportion of subjects having surgical site infection through 12 months as determined by CDC guidelines</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Tibial Fractures</condition>
  <arm_group>
    <arm_group_label>BHA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects treated with BHA + standard of care</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Subjects treated as per standard of care</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>BHA</intervention_name>
    <description>BHA active ingredients include a blood-derived component and beta-tricalcium phosphate. It is applied directly to the bone fracture and nearby viable bone at the time of wound closure.</description>
    <arm_group_label>BHA</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        In order to be eligible to participate in this study, subjects must meet all of the&#xD;
        following criteria:&#xD;
&#xD;
          1. Patient is between the ages of 18-75 inclusive at time of randomization.&#xD;
&#xD;
          2. Patient has an acute open Gustilo-Anderson Type IIIA or IIIB fracture of the tibia&#xD;
             shaft, with or without a fibula fracture, secondary to trauma.&#xD;
&#xD;
          3. Patient received antibiotic treatment within 2 hours of presentation at initial&#xD;
             medical facility.&#xD;
&#xD;
          4. Patient underwent their first operative debridement within 24 hours of presentation at&#xD;
             initial medical facility.&#xD;
&#xD;
          5. Patient is scheduled to have DWC within 14 days of initial injury.&#xD;
&#xD;
          6. The tibia fracture requires open fracture reduction and internal fixation with&#xD;
             intramedullary (IM) nailing;&#xD;
&#xD;
               -  IM nailing has been cross-locked for stability with a 4-5mm interlock, with a&#xD;
                  minimum of 1 static screw above the fracture site and 1 static screw below the&#xD;
                  fracture site, and&#xD;
&#xD;
               -  All IM nails have a diameter between 8.5-12mm with 1.0-1.5mm over-reaming of the&#xD;
                  canal.&#xD;
&#xD;
             The temporary use of external fixation prior to IM rodding and DWC is allowed.&#xD;
&#xD;
          7. Upon stabilization of the tibia fracture, the patient has a cortical deficit of less&#xD;
             than or equal to 1.0cm involving no more than 50% of the tibia circumference. The&#xD;
             cortical deficit of the residual 50% circumference must be less than 1.0cm. Gap&#xD;
             assessments to be made with calibrated radiographs or visual inspection. In addition,&#xD;
             patients are not likely to require a secondary procedure(s) to promote bone healing.&#xD;
&#xD;
          8. BHA is able to be applied through existing soft tissue defects created by the injury&#xD;
             or those created during surgical treatment. No new incisions should be required&#xD;
             specifically for application of BHA.&#xD;
&#xD;
          9. Patient is willing and able to comply with all study procedures including all&#xD;
             pre-operative, post-operative and rehabilitation requirements.&#xD;
&#xD;
         10. Patient is able to give voluntary IC to participate and has signed an IC form specific&#xD;
             to this study prior to study treatment and DWC.&#xD;
&#xD;
         11. Patients of childbearing potential must use adequate methods of contraception during&#xD;
             the duration of follow-up (12-months). Adequate methods include abstinence, female and&#xD;
             male sterilization, hormonal contraceptives, intrauterine devices (IUDs), implants,&#xD;
             injectables, and double barrier methods.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who are currently participating in another investigational trial or having&#xD;
             participated in a clinical investigation within the last 90 days or intend to during&#xD;
             the course of the study.&#xD;
&#xD;
          2. Patients who are currently prisoners.&#xD;
&#xD;
          3. Patients who are unable to give informed consent.&#xD;
&#xD;
          4. Patients who are skeletally immature (&lt;18 years of age or radiographic evidence of&#xD;
             open tibial physes).&#xD;
&#xD;
          5. Patients with Type I, II, or IIIC open tibia fractures according to the&#xD;
             Gustilo-Anderson classification.&#xD;
&#xD;
          6. Current injury is a pathological fracture.&#xD;
&#xD;
          7. Patients with additional injuries that could impact their ability to complete the&#xD;
             required assessments and postoperative rehabilitation. Examples include but are not&#xD;
             limited to the following:&#xD;
&#xD;
               1. Head injury with impaired cognitive function,&#xD;
&#xD;
               2. Spinal injury with resultant neurologic weakness or paralysis,&#xD;
&#xD;
               3. Multi-trauma requiring prolonged hospitalization or recovery that, in the opinion&#xD;
                  of the investigator, the treatment and/or rehabilitation of such injuries will&#xD;
                  substantially interfere with the treatment, rehabilitation or other requirements&#xD;
                  outlined in this protocol,&#xD;
&#xD;
               4. Concomitant ipsilateral or contralateral lower extremity injury/fracture(s) if,&#xD;
                  in the opinion of the investigator, the treatment and/or rehabilitation of such&#xD;
                  fracture(s) will substantially interfere with the treatment, rehabilitation or&#xD;
                  other requirements outlined in this protocol.&#xD;
&#xD;
               5. Sustained severe burns (&gt;10% total body surface area [TBSA] or &gt;5% TBSA with full&#xD;
                  thickness or circumferential injury)&#xD;
&#xD;
               6. Compartment syndrome of the leg diagnosed preoperatively&#xD;
&#xD;
          8. Patients with pre-existing conditions, mental/psychosocial disorders, or who are&#xD;
             taking medication that may delay or impair the fracture healing process or that could&#xD;
             impact their ability to return for follow-up visits and/or complete the required&#xD;
             assessments and postoperative rehabilitation. Examples include but are not limited to&#xD;
             the following:&#xD;
&#xD;
               1. Renal insufficiency with serum creatinine of 3.5 mg/dL or higher or being treated&#xD;
                  with renal dialysis,&#xD;
&#xD;
               2. Uncontrolled diabetes mellitus with A1C of greater than or equal to 10%,&#xD;
&#xD;
               3. Serum Aspartate Aminotransferase (AST) greater than 2 times the upper limit of&#xD;
                  normal or diagnosed hepatitis C or hepatitis B,&#xD;
&#xD;
               4. Neurological or neuromuscular disorders affecting ambulatory capability or&#xD;
                  cognition, such as Parkinson's disease, myasthenia gravis, or stroke with&#xD;
                  relevant residual neurological deficit,&#xD;
&#xD;
               5. Current medications that could interfere with fracture healing such as systemic&#xD;
                  corticosteroids,&#xD;
&#xD;
               6. Morbid Obesity with BMI greater than or equal to 40 kg/m2,&#xD;
&#xD;
               7. A current endocrine or metabolic disorder known to affect osteogenesis (e.g.,&#xD;
                  Paget's disease, renal osteodystrophy, hyperthyroidism, parathyroid hormone&#xD;
                  disorder, Ehler-Danlos syndrome, osteogenesis imperfecta, or Cushing's disease),&#xD;
&#xD;
               8. History of osteomyelitis of index lower extremity or evidence of active soft&#xD;
                  tissue or bone infection at this site of injury at the time of DWC,&#xD;
&#xD;
               9. Patients with immune deficiency or history of auto-immune disease.&#xD;
&#xD;
          9. Patients with an active malignancy or a history of any invasive malignancy (except&#xD;
             non-melanoma skin cancer), unless the patient has been treated with curative intent&#xD;
             and there have been no clinical signs or symptoms of malignancy for at least 5 years.&#xD;
&#xD;
         10. Patients with any medical condition or life circumstances that in the surgeon's&#xD;
             opinion could impact their ability to return for follow-up visits and/or complete the&#xD;
             required assessments and postoperative rehabilitation. Examples include but are not&#xD;
             limited to the following:&#xD;
&#xD;
               1. Patient lives too far away making the return for study visits to the surgeon's&#xD;
                  facility unlikely,&#xD;
&#xD;
               2. The patient has known alcohol or drug abuse within 3 months of screening to a&#xD;
                  degree that makes it unlikely the patient will follow study requirements.&#xD;
&#xD;
         11. Patients who are known to have anaphylactic or severe systemic reaction to human blood&#xD;
             products, genipin, β-TCP, glycerin or to other components of the investigative product&#xD;
             formulation.&#xD;
&#xD;
         12. Female patients of child-bearing potential who meet any of the following criteria:&#xD;
&#xD;
               -  Patient is currently pregnant (prior diagnosis or a positive pregnancy test at&#xD;
                  baseline), or planning to become pregnant any time during the course of the study&#xD;
&#xD;
               -  Currently breastfeeding or planning to breastfeed at any time during the course&#xD;
                  of the study&#xD;
&#xD;
         13. Upon stabilization of the tibia fracture, the patient has a bone gap greater than&#xD;
             1.0cm apparent by calibrated radiographs or by visual inspection and/or the patient is&#xD;
             highly likely to require secondary intervention procedure(s), surgical or nonsurgical&#xD;
             (e.g., bone stimulation or ultrasound treatment) for the index fracture.&#xD;
&#xD;
         14. Patients who have mal-alignment post-IM nailing of &gt;10° in the coronal plane or &gt;15°&#xD;
             in the sagittal plane.&#xD;
&#xD;
         15. Patients who received only plates and screws for tibia fracture stabilization.&#xD;
&#xD;
         16. At the time of the DWC surgery, patients who have a planned secondary intervention&#xD;
             procedure, surgical or nonsurgical (e.g., bone stimulation or ultrasound treatment)&#xD;
             for the index fracture.&#xD;
&#xD;
         17. Patients being treated with any form of local antibiotics at the time of DWC.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janet M Vargo, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Carmell Therapeutics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Carmell Therapeutics</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>January 29, 2019</study_first_submitted>
  <study_first_submitted_qc>January 30, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <last_update_submitted>January 21, 2020</last_update_submitted>
  <last_update_submitted_qc>January 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fractures, Bone</mesh_term>
    <mesh_term>Tibial Fractures</mesh_term>
  </condition_browse>
  <!-- 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/NCT03826784
org study id: CAR-BHA-U31
nct id: NCT03826784
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: Yes
is unapproved device: Yes
This clinical study is being conducted to demonstrate the safety and effectiveness of the
      Bone Healing Accelerant (BHA) product when applied to tibia (leg bone) fractures with an
      external wound or skin break (also called open tibia fractures). It is hypothesized that by 6
      months, the number of subjects with successful bone healing will be greater in the
      BHA-treated group compared to subjects treated with standard of care alone. Open tibia
      fractures were chosen for this study because healing rates are typically longer than for
      other bone fractures due to the limited vascular supply, limited soft tissue coverage, and
      higher risk of infection.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Composite healing measure
time frame: 6 months
description: Proportion of subjects in each arm meeting the healing success criteria. A binary (Yes/No) outcome for overall healing will be derived from the following three outcomes: Radiographic healing as measured by a score of at least 13 on the modified Radiographic Union Scale in Tibia fractures (mRUST, range bad to good 1-16), ambulation as measured by a score of at least 2 on the Function IndeX for Trauma scale (range bad to good 0-3), and no secondary intervention to promote bone healing. All three components must be met for a "yes" on composite healing.
measure: Radiographic healing
time frame: 6 months
description: Population mean Modified Radiographic Union Scale in Tibia Fractures (mRUST) scores (range bad to good is 4-16)
measure: Secondary intervention (surgical or nonsurgical)
time frame: 6 months
description: Proportion of subjects not having secondary intervention conducted specifically to promote bone healing needed
measure: Surgical site infection
time frame: 12 months
description: Proportion of subjects having surgical site infection through 12 months as determined by CDC guidelines
arm group label: BHA
arm group type: Experimental
description: Subjects treated with BHA + standard of care
arm group label: Control
arm group type: No Intervention
description: Subjects treated as per standard of care
intervention type: Combination Product
intervention name: BHA
description: BHA active ingredients include a blood-derived component and beta-tricalcium phosphate. It is applied directly to the bone fracture and nearby viable bone at the time of wound closure.
arm group label: BHA
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Janet M Vargo, PhD
role: Study Director
affiliation: Carmell Therapeutics
facility: 
country: United States
responsible party type: Sponsor
mesh term: Fractures, Bone
mesh term: Tibial Fractures