Clinical trial NCT01756326: Study on Autologous Osteoblastic Cells Implantation in Hypotrophic Non-Union Fractures
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Long Bone Non-Union
Keywords: Non-Union Fractures
Impaired Healing
Fractures
Orthopedics
Bone
Musculoskeletal Disorders
Lead sponsor: Bone Therapeutics S.A
Sponsor class: INDUSTRY
First posted: 2012-12-25
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Global Disease Evaluation as perceived by the patient using a Visual Analogue Scale
timeFrame: 12 months
measure: Radiological healing progression using the RUS(T) as assessed by CT scan
timeFrame: 12 months
measure: 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
timeFrame: 12 months
Secondary outcomes:
measure: Pain using a Visual Analogue Scale
timeFrame: 12 months
measure: Weight-bearing using Likert Scale
timeFrame: 12 months
measure: Well-being score as assessed by the SF-12 questionnaire
timeFrame: 12 months
measure: Radiological improvement using the RUS(T) as assessed by X-ray
timeFrame: 12 months
Other outcomes:
Locations:
city: Anderlecht
country: Belgium
facility: Investigating site BE01
city: Brugge
country: Belgium
facility: Investigating site BE05
city: Brussels
country: Belgium
facility: Investigating site BE09
city: Charleroi
country: Belgium
facility: Investigating site BE02
city: Genk
country: Belgium
facility: Investigating site BE04
city: Gent
country: Belgium
facility: Investigating site BE06
city: Hasselt
country: Belgium
facility: Investigating site BE07
city: Mons
country: Belgium
facility: Investigating site BE08
city: Ottignies
country: Belgium
facility: Investigating site BE03
city: Amiens
country: France
facility: Investigating site FR01
city: Bordeaux
country: France
facility: Investigating site FR04
city: Evry
country: France
facility: Investigating site FR06
city: Paris
country: France
facility: Investigating site FR03
city: Rouen
country: France
facility: Investigating site FR02
city: Maastricht
country: Netherlands
facility: Investigating site NL02
city: Rotterdam
country: Netherlands
facility: Investigating site NL01
Study officials:
References: