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

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

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.

Study Overview

• Status: Terminated
• Conditions: Long Bone Non-Union
• Intervention / Treatment: Drug: PREOB® Implantation; Procedure: Bone Autograft

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Anderlecht, Belgium
    • Investigating site BE01
  • Brugge, Belgium
    • Investigating site BE05
  • Brussels, Belgium
    • Investigating site BE09
  • Charleroi, Belgium
    • Investigating site BE02
  • Genk, Belgium
    • Investigating site BE04
  • Gent, Belgium
    • Investigating site BE06
  • Hasselt, Belgium
    • Investigating site BE07
  • Mons, Belgium
    • Investigating site BE08
  • Ottignies, Belgium
    • Investigating site BE03
• France
  • Amiens, France
    • Investigating site FR01
  • Bordeaux, France
    • Investigating site FR04
  • Evry, France
    • Investigating site FR06
  • Paris, France
    • Investigating site FR03
  • Rouen, France
    • Investigating site FR02
• Netherlands
  • Maastricht, Netherlands
    • Investigating site NL02
  • Rotterdam, Netherlands
    • Investigating site NL01

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Bone Therapeutics S.A

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2019

Study Registration Dates

• First Submitted: December 20, 2012
• First Submitted That Met QC Criteria: December 24, 2012
• First Posted (Estimate): December 25, 2012

Study Record Updates

• Last Update Posted (Actual): June 11, 2020
• Last Update Submitted That Met QC Criteria: June 9, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Bone; Musculoskeletal Disorders; Fractures; Orthopedics; Non-Union Fractures; Impaired Healing
• Additional Relevant MeSH Terms: Fractures, Bone; Wounds and Injuries; Fractures, Ununited
• Other Study ID Numbers: PREOB-NU3