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

Phase 2

Terminated

• Conditions: Long Bone Non-Union
• Interventions: Procedure: Bone Autograft; Drug: PREOB® Implantation

• Registration Number: NCT01756326
• Lead Sponsor: Bone Therapeutics S.A

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-06
• Study First Submitted: 2012-12-20
• Study First Submitted QC: 2012-12-24
• Study First Posted: 2012-12-25
• Primary Completion: 2018-04
• Study Completion: 2019-04
• Status Verified: 2020-06
• Last Update Submitted: 2020-06-09
• Last Update Posted: 2020-06-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 5

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bone Autograft	Bone Autograft	Each patient will be treated by Bone Autograft according to standard-of-care procedure of the investigating site.
PREOB® Implantation	PREOB® Implantation	Each patient will undergo a single administration of PREOB® into the non-union site, under local or loco-regional anesthesia.

Primary Outcome Measures

Name	Time	Method
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
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

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (16)

Investigating site BE04; 🇧🇪 Genk, Belgium

Investigating site FR03; 🇫🇷 Paris, France

Investigating site BE01; 🇧🇪 Anderlecht, Belgium

Investigating site BE05; 🇧🇪 Brugge, Belgium

Investigating site BE09; 🇧🇪 Brussels, Belgium

Investigating site BE02; 🇧🇪 Charleroi, Belgium

Investigating site BE06; 🇧🇪 Gent, Belgium

Investigating site BE07; 🇧🇪 Hasselt, Belgium

Investigating site BE08; 🇧🇪 Mons, Belgium

Investigating site FR01; 🇫🇷 Amiens, France

Investigating site BE03; 🇧🇪 Ottignies, Belgium

Investigating site FR04; 🇫🇷 Bordeaux, France

Investigating site FR06; 🇫🇷 Evry, France

Investigating site FR02; 🇫🇷 Rouen, France

Investigating site NL02; 🇳🇱 Maastricht, Netherlands

Investigating site NL01; 🇳🇱 Rotterdam, Netherlands