Tibial fracture considered at risk of DU/NU (based on the combination of risk factors documented to be associated with increased proportion of DU/NU). MedDRA version: 20.0 Level: PT Classification code 10043827 Term: Tibia fracture System Organ Class: 10022117 - Injury, poisoning and procedural complications
Conditions
Sponsors
Bone Therapeutics S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All subjects must satisfy ALL of the following criteria to be included in the study: 1. Men and women at least 18 years of age 2. Subject diagnosed with a fresh proximal, midshaft or distal tibial fracture with stable definitive reduction and stabilization performed with nail(s) and wound closure (as required) within 14 days of fracture occurrence. This time window of 14 days allows for potential intermediate stabilization, wound cleaning and closure. 3. Factor(s) at risk of DU/NU: - Mechanism of injury: High energy impact fracture OR - Any 2 of following patient-related factors: current smoker, chronic NSAID use, high Body Mass Index BMI (>30), polytrauma 4. Soft-tissue injury pattern including: - Severe open fracture (Gustilo-Anderson grade IIIa and IIIb) OR - Open fracture (Gustilo-Anderson grade I-II) with at least one additional risk (current smoker, chronic NSAID use, high BMI (>30), polytrauma, comminuted fracture or cortical continuity =50%) OR - Closed fracture (Tscherne grade I-III) with at least one additional risk (current smoker, chronic NSAID use, high BMI (>30), polytrauma, comminuted fracture or cortical continuity = 50%) The following fracture patterns are included based on the 2018 AO online classification system: - 41A (Proximal Extraarticular) includes 41A1; 41A2; 41A3 - 42A (Simple Diaphyseal) includes 42A1; 42A2; 42A3 - 42B (Wedge Fracture) includes 42B2; 42B3 (also called butterfly fracture) - 43A (Distal extra-articular) includes 43A1; 43A2; 43A3 (and all sub-components) 5. Ability to obtain a written, dated, and signed informed consent prior to any study related procedures and ability to understand and comply with study requirements Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 160 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: Current symptoms and/or signs related to the disease under study: 1. Definitive reduction at the fracture site under investigation performed with plate, screw, or external fixator (Note: It is acceptable to first stabilize the fracture with an external fixator prior to definitive stabilization with intramedullary nail) 2. Subjects who did not receive a standard antibiotic prophylaxis before definitive reduction at the fracture site under investigation 3. Intra-articular tibial pilon and/or plateau fracture at the site under investigation (i.e., AO classification 41B; 41C; 43B; 43C) 4. Known osteomyelitis at the fracture site under investigation 5. Residual bone defect post-definitive reduction greater than 1cm at least on 2 cortices at the fracture site under investigation 6. Fracture requiring vascular surgery at the site under investigation 7. Pathological fractures as judged by the Investigator, such as tumor or metabolic bone disease 8. Multi-segmental fracture at the site under investigation (where there are more than 2 separate segments and thus requiring more than a single dose of the investigational product) Current or previous diagnoses, signs and/or symptoms: 9. Presence of fever (defined as body temperature = 38°C) or other signs/symptoms suggestive of active systemic infection before randomization 10. Severe brain trauma with a Glasgow Coma Scale (GCS) [3 – 8] or severe spinal cord injury with impossibility of weight-bearing 11. Current or history (within 5 years) of any neoplasia (except for basal cell carcinoma of the skin and for carcinoma in situ of the cervix that has been treated with no evidence of recurrence) 12. Known metabolic diseases potentially interfering with bone healing as judged by the Investigator, such as thyroid dysfunction, Paget disease or severe osteoporosis 13. Planned or history of solid organ transplantation or bone marrow transplantation 14. Known disease, including genetic disease, that may possibly need solid organ transplantation 15. Subject with renal impairment requiring dialysis or with clinically significant renal impairment defined as serum creatinine >2.0 x ULN 16. Clinically significant hepatic function impairment defined as ALT/AST levels > 3x ULN or total bilirubin levels > 2 x ULN 17. Known hematologic disease as evidenced by hematocrit < 25%, white blood cell < 2,500/µl or platelet values < 100,000/µl without another explanation 18. Subject with an history of long standing poorly controlled chronic hypertension or diabetes that could put him at risk of needing a kidney transplant later on according to the Investigator 19. History of hypersensitivity to human biological material including blood and blood derived products 20. Known allergy to DMSO, dextran, gentamicin and any other aminoglycosides Current or previous treatment: 21. Participation in another interventional clinical study within 3 months prior to screening 22. Any chronic intake of medication within one month that might affect bone metabolism or the quality of bone formation such as but not limited to bisphosphonates, teriparatide, systemic steroids, anticoagulant therapies, methotrexate and other immunosuppressant drugs or related immunotherapy 23. Previous (within 10 years) treatment with bisphosphonates 24. Current treatment with bone morphogenic protein or any other osteo-biologic intervention at the site of the tibial fracture Safety aspects concerning female subjects of childbearing potential
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that treatment with ALLOB leads to a significant improvement in radiological success with respect to placebo in subjects with a tibial fracture.;Secondary Objective: Secondary objectives: - To assess the impact of ALLOB on the speed of fracture healing, radiological fracture healing and clinical fracture healing - To assess the impact of ALLOB on the rate of fracture healing, radiological fracture healing, clinical fracture healing, DU and NU - To assess the impact of ALLOB on the rate of rescue intervention due to tibial DU and NU - To assess the impact of ALLOB on functional status and return to normal activities - To assess the impact of ALLOB on RUST score - To assess the accuracy of RUST threshold value predictive of bone healing - To demonstrate the overall safety of ALLOB particularly based on key safety outcomes (product failure, infection related to implantation, hypersensitivity reaction, ectopic bone formation) ;Primary end point(s): The primary endpoint is the proportion of subjects with a radiological success at Week 12 (Visit #4). A radiological success is defined as a subject with a RUST score above the threshold value predictive of a normal bone healing. The threshold value that would best predict bone healing is hypothesized to be between 6 and 8 (on a scale from 4 to 12). It will be selected at an interim analysis by an Independent Data Monitoring Committee (IDMC) based on predefined decision rules.;Timepoint(s) of evaluation of this end point: 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy endpoints: Key efficacy secondary endpoints: - Proportion of subjects with radiological success at Week 16 (Visit #5), Week 20 (Visit #6) and Month 6 (Visit #7) - Change in RUST at Week 12 (Visit #4), Week 16 (Visit #5), Week 20 (Visit #6) and Month 6 (Visit #7) compared to baseline visit Other efficacy secondary endpoints: - Time to fracture healing: based on Investigator judgement, fracture healing is defined by a full weight bearing of the treated tibia, a lack of pain at palpation, and a radiological fracture union. Radiological fracture union is defined by a bone bridging on at least three of the four cortices and absence of fracture line - Time to clinical fracture healing: based on Investigator judgement with the condition of a full weight bearing of the treated tibia and a lack of pain at palpation - Time to radiological fracture healing: performed by Independent Radiologists with the condition of a radiological fracture union - Proportion of subjects with fracture healing at each follow-up visit - Proportion of subjects with clinical fracture healing at each follow-up visit - Proportion of subjects with radiological fracture healing at each follow-up visit - Proportion of subjects with full weight-bearing at each follow-up visit - Time to rescue intervention - Time to full weight-bearing - Proportion of subjects requiring rescue intervention within 12 months - Proportion of subjects diagnosed with NU at Month 9 (Visit #8) - Proportion of subjects diagnosed with DU at Week 20 (Visit #6) - Pain at palpation at each follow-up visit - Lower Extremity Functional Scale (LEFS) score at each follow-up visit - Short Form 12 (SF-12) score at each follow-up visit - Sensitivity and specificity of RUST threshold value at 6 months predictive of bone healing with regard to fracture outcome Safety endpoints: - Any Adverse Event (AE)/Serious Adverse Event (SAE) - Adverse Event of Special Interest (AESI): o Suspe | — |
Countries
Belgium, Czech Republic, France, Germany, Hungary, Poland, Spain
Contacts
Public ContactClinical Trial Team
Bone Therapeutics S.A.
Outcome results
None listed