Safety and Performance of BonyPid-1000™ in the Treatment of Gustilo I, II, IIIA and IIIB Tibial Open Fractures

Study Overview
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Brief Summary
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This is a prospective, multi-national, multicenter, randomized, two arms, single blind, Standard of Care (SOC) controlled, with blinded central reading center study. This study will assess the safety and performance of BonyPid-1000™ in severe open tibial fractures (Gustilo IIIA and IIIB) when implanted as adjunct to SOC and compared to SOC alone.

Detailed Description
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The study population include subjects with a classification of Gustilo I, II, IIIA or IIIB of tibial open fractures, assigned for surgical procedure, who meet eligibility criteria and provide signed informed consent. Subjects will be randomized into either Study investigational arm or Study control arm, using a 1:1 ratio. Randomization will be stratified by Gustilo classification (I and II; IIIA ; IIIB). Total duration of the study is expected to be approximately 32 months from first subject enrolled until last subject completed. It is expected that each subject will be in the study for approximately 52 weeks Subjects will be followed at the following time points: Immediately post index procedure During hospitalization Discharge visit 4 weeks and then monthly up to 24 weeks, 36 and at 52 weeks. This is a single blind clinical trial. Subjects and their family members will be blinded to the treatment arms assignment. The study site personnel present at the baseline procedure as well as the physician performing the procedure will be trained not to disclose the treatment arm to the subject, his/her family, and to health care providers outside of the Orthopedic department. An independent X-ray reading center assessing all subjects' images will be blinded to the treatment arms assignments, for the entire trial period. However, due to the radiographic appearance of the BonyPid-1000 as compared to SOC may differ, it is not entirely possible to blind the evaluating radiologists.

Official Title
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Safety and Performance of BonyPid-1000™ in the Treatment of Gustilo I, II, IIIA and IIIB Tibial Open Fractures

Conditions
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Tibial Fractures, Open Fractures

Intervention / Treatment
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* Device: BonyPid-1000
* Other: Standard of Care (SOC) treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant female aged between 18 to 70 years of age. Female of childbearing potential should have a negative urine pregnancy test prior to index procedure Note: All female of childbearing potential must agree to use a highly effective method of contraception consistently and correctly for the duration of the study. Subjects with tibia open fractures of Gustilo grade I, II, IIIA or IIIB, who are assigned for surgery and are suitable for bone filler implantation, are eligible to participate in the study. Single or multi-injured subjects who are hemodynamically and physiologically stable. Note: A multi-injured subject is defined as one who sustains ≥2 injuries, each injury requiring hospitalization, independently of the presence of other injuries. Subjects who are able and willing to sign an informed consent form, prior to any protocol-specific procedures being performed and accept to comply with protocol requirements for the duration of the study. In specific cases, due to medical condition (e.g. a medical condition which necessitate an immediate medical treatment), a shortened consenting process may take place in accordance with local regulations. Exclusion Criteria: Female who is pregnant or breastfeeding. Subjects with known current disseminated malignancies, active cancer or autoimmune diseases. Note: active cancer defined as - cancer for which therapeutic or palliative treatment is either ongoing at the time of enrolment or has stopped less than six (6) months before enrolment. Subjects with fractures due to known medical history of Osteoporosis. Subject with known medical history of Diabetes. Heavy smokers (a smoker with a daily cigarettes consumption of more than 20 pieces) in the last 6 months. Drug/alcohol abusers Acute infection in another sites/organs. Non-ambulating subjects prior to the trauma. More than 24 hours between injury and systemic antibiotic treatment initiation Subjects with bone fracture due to known medical history of metabolic bone diseases. Subjects with high velocity gunshot bone fractures. Subjects with major intra-articular fractures Subjects with hypersensitivity to doxycycline and or tetracycline family of drugs. Subjects treated with systemic doxycycline during the last 4 weeks prior to screening. Previous surgical intervention in the target tibia Subject with previous open fractures within one year in the target tibia Subjects currently receiving or have received an investigational product in the last 30 days and/or participate in another clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be randomized into either Study investigational arm or Study control arm, using a 1:1 ratio. Randomization will be stratified by Gustilo classification (I and II; IIIA ; IIIB). In the study treatment arm patients will receive BonyPid-1000 in addition to the standard of care treatment. in the control arm patients will receive the standard of care treatment alone.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BonyPid-1000<br>Implantation of BonyPid-1000 medical device, constructed of bone filler coated with controlled release antibiotic formulation, concomitantly with standard of care treatment (SOC) | Device: BonyPid-1000<br>* BonyPid-1000 implantation concomitantly to standard of care (SOC) treatment<br>Other: Standard of Care (SOC) treatment<br>* Standard of Care (SOC) treatment only<br>|
| Other: Study control arm<br>Standard of care treatment (SOC) only | Other: Standard of Care (SOC) treatment<br>* Standard of Care (SOC) treatment only<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Deep Infection in the target fracture site | Deep Infection in the target fracture site during the 4 weeks post index procedure. The endpoint will be assessed by calculating the rate /percent per group. | During the 4 weeks post index procedure | 
| Performance: Radiographic-assessed bone healing | Radiographic-assessed bone healing during the 24-week follow-up period, based on independent blinded central radio-graphic evaluations of the target fracture's X-rays. | During the 24-week follow-up period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Performance: Time to Radiographic-assessed bone healing | Time to radiographic-assessed bone healing, based on independent blinded central radio-graphic evaluations of the target fracture's X-rays. | During the 24-week follow-up period |