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

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.

Study Overview

• Status: Completed
• Conditions: Tibial Fractures; Open Fractures
• Intervention / Treatment: Device: BonyPid-1000; Other: Standard of Care (SOC) treatment

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Be'er Sheva', Israel
    • Soroka Medical Center
  • Haifa, Israel, 31096
    • Rambam Health Care Campus
  • Jerusalem, Israel
    • Hadassah University Hospital
  • Tel Aviv, Israel, 64239
    • The Tel Aviv Sourasky Medical Center
  • Tel Hashomer, Israel, 5262100
    • The Chaim Sheba Medical Center
  • Merkaz
    • Petah Tiqva, Merkaz, Israel
      • Rabin Medical Center
• Philippines
  • Cavite, Philippines
    • De La Salle HSI
  • Manila City, Philippines
    • Philippines General Hospital
  • Quezon City, Philippines
    • Philippine Orthopedic Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or non-pregnant female aged between 18 to 70 years of age.
2. 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.
3. 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.

4. 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.

5. 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:

1. Female who is pregnant or breastfeeding.
2. 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.
3. Subjects with fractures due to known medical history of Osteoporosis.
4. Subject with known medical history of Diabetes.
5. Heavy smokers (a smoker with a daily cigarettes consumption of more than 20 pieces) in the last 6 months.
6. Drug/alcohol abusers
7. Acute infection in another sites/organs.
8. Non-ambulating subjects prior to the trauma.
9. More than 24 hours between injury and systemic antibiotic treatment initiation
10. Subjects with bone fracture due to known medical history of metabolic bone diseases.
11. Subjects with high velocity gunshot bone fractures.
12. Subjects with major intra-articular fractures
13. Subjects with hypersensitivity to doxycycline and or tetracycline family of drugs.
14. Subjects treated with systemic doxycycline during the last 4 weeks prior to screening.
15. Previous surgical intervention in the target tibia
16. Subject with previous open fractures within one year in the target tibia
17. Subjects currently receiving or have received an investigational product in the last 30 days and/or participate in another clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BonyPid-1000; 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; BonyPid-1000 implantation concomitantly to standard of care (SOC) treatment; Other: Standard of Care (SOC) treatment; Standard of Care (SOC) treatment only
Other: Study control arm; Standard of care treatment (SOC) only	Other: Standard of Care (SOC) treatment; Standard of Care (SOC) treatment only

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: PolyPid Ltd.
• Investigators: Study Director: Shany Blum, Dr., PolyPid Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): September 1, 2018
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: July 2, 2015
• First Submitted That Met QC Criteria: July 6, 2015
• First Posted (Estimate): July 7, 2015

Study Record Updates

• Last Update Posted (Actual): May 19, 2020
• Last Update Submitted That Met QC Criteria: May 17, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Leg Injuries; Fractures, Bone; Tibial Fractures; Fractures, Open
• Other Study ID Numbers: BonyPid-1000TM-103