A pivotal Phase IIb/III, multicentre, randomised, open, controlled study on the efficacy and safety of autologous osteoblastic cells (PREOB®) implantation in non-infected hypotrophic non-union fractures.

Pseudoarthrosis is a bone disorder characterised by a failure of the fracture
to heal within 6 months after the fracture occured. The normal time for
fracture healing is about 3 months. Possible causes for pseudoarthrosis can be
poor fracture stabilisation or local infection. When these causes are excluded,
the reason for this impaired fracture healing seems to be a failure of sepcific
bone cells ( called osteoblasts) to multiply. Currently, the most common
treatment involves surgery done under general anesthesia during which a piece
of bone is taken from the pelvis to be reimplanted directly at the site of the
pseudoarthrosis. This treatment also known as autologous bone graft, generates
good results but requires major surgery of several hours under general
anesthesia, followed by about 4 to 5 days of hospitalisation.

To determine the efficacy and the safety of PREOB, a proprietary population of
autologous bone-forming cells, in the treatment of non-infected hypotrophic
non-union fractures of long bones.

The study will be performed over two years as a randomised, open, controlled
intervention study. A total of 210 patients with non-infected hypotrophic
non-union fractures of long bones will be randomized into 2 study arms: 105
patients in the PREOB group and 105 patients in the conservative treatment
group. The study will consist of maximum 9 visits and 2 follow-up phone calls.

Study part 1:
Study group: percutaneous injection of 2, 3, or 4 ml PREOB suspension
(depending on the fracture interline, at a concentration of 4 x 10E6 cells/ml)
using a 3 mm trephine into the fracture site.
Control group: no intervention.

Study part 2:
Study group: percutaneous injection of 2, 3, or 4 ml PREOB suspension
(depending on the fracture interline, at a concentration of 4 x 10E6 cells/ml)
using a 3 mm trephine into the fracture site.
Control group: bone autograft surgery following standard of care practices of
the centre.

A randomised patient will undergo the following procedures during the study:
- 9 blood samples
- 11 x SF-12 questionnaire (also 2x during follow-up period)
- 7 x X-ray of the fracture
- 5 x CT of the fracture
For participating women, a pregnancy test will be performed at each visit.

The burden associated with study participation, besides the standard
procedures, lay mainly with the bone marrow and blood sampling.
There is more consulting and medical imaging (X-ray and CT), besides extra lab
testing.
The questionnaires patients have to complete, can also be seen as a burden.