Study to Assess the Efficacy and Safety of ALLOB in Tibial Fracture

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 178

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

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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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