Study on Autologous Osteoblastic Cells Implantation in Hypotrophic Non-Union Fractures

Study Overview
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Brief Summary
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Fracture healing is a complex physiological process caused by interaction of cellular elements, cytokines and signaling proteins, which results in the formation of new bone (Gerstenfeld et al., 2003). Depending on fracture site, complexity, co-morbidities and other factors, 10% of all fractures will eventually fail to unite. Non-union fractures are defined as fractures that are at least six to nine months old and in which there have been no signs of healing for the last three months. Various causes have been evoked for impaired healing in hypotrophic (atrophic and oligotrophic) non-unions, including poor fracture stabilization, local infection and failure of the osteoblastic cells to multiply. Currently the treatment of choice for non-unions, particularly atrophic non-unions, is bone autograft (or allograft), combined or not with intramedullary nailing, plating, and external fixation devices (Kanakaris et al., 2007). This procedure produces good results but requires an invasive surgery of several hours under general anesthesia and a few days of hospitalization. Because of this, major complications have been reported in up to 20-30% of patients (Pieske et al., 2009, Zimmerman et al., 2009). This Phase 2b/3 study aims at demonstrating the safety and efficacy of PREOB®, a proprietary population of autologous osteoblastic cells, in the treatment of hypotrophic non-union fractures of long bones. PREOB® will be compared to Bone Autograft in a non-inferiority design.

Official Title
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A Pivotal Phase 2b/3, Multicentre, Randomised, Open, Controlled Study on the Efficacy and Safety of Autologous Osteoblastic Cells (PREOB®) Implantation in Non-Infected Hypotrophic Non-Union Fractures

Conditions
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Long Bone Non-Union

Intervention / Treatment
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* Drug: PREOB® Implantation
* Procedure: Bone Autograft


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to provide a written, dated, and signed informed consent prior to any study related procedure, and to understand and comply with study requirements Diagnosis of a non-infected hypotrophic non-union fracture of a long bone of at least 6 months at the time of treatment Normal hematology function Exclusion Criteria: Positive serology for HIV, hepatitis B, hepatitis C, syphilis, HTLV-1 Presence or previous history, or risk factors for diseases caused by prions Renal impairment, hepatic impairment Patient with poorly controlled diabetes mellitus, severe arterial diseases and/or neuropathy Insufficient fracture stability Recent osteosynthesis material or bone graft Multifocal fracture/non-unions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PREOB® Implantation<br>Each patient will undergo a single administration of PREOB® into the non-union site, under local or loco-regional anesthesia. | Drug: PREOB® Implantation<br> <br> |
| Active Comparator: Bone Autograft<br>Each patient will be treated by Bone Autograft according to standard-of-care procedure of the investigating site. | Procedure: Bone Autograft<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Disease Evaluation as perceived by the patient using a Visual Analogue Scale |  | 12 months | 
| Radiological healing progression using the RUS(T) as assessed by CT scan |  | 12 months | 
| Potential occurrence of any AE or SAE, related to the product or to the procedure, using patient open non-directive questionnaire, physical examination and laboratory measurements |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain using a Visual Analogue Scale |  | 12 months | 
| Weight-bearing using Likert Scale |  | 12 months | 
| Well-being score as assessed by the SF-12 questionnaire |  | 12 months | 
| Radiological improvement using the RUS(T) as assessed by X-ray |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Union Fractures, Impaired Healing, Fractures, Orthopedics, Bone, Musculoskeletal Disorders