focus resources in the allogeneic platform and provide optimal value for patients

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.

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