Long Bone Non-UnionPhase 2/3NCT01756326
Study on Autologous Osteoblastic Cells Implantation in Hypotrophic Non-Union Fractures
A Phase 2/3 study testing PREOB® Implantation and Bone Autograft in people with Long Bone Non-Union, run by Bone Therapeutics S.A at 16 sites in 3 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Long Bone Non-Union
- What is being tested?
- PREOB® Implantation and Bone Autograft
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 16 sitesin 3 countries
- Study dates
- Jun 2012to Apr 2019
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
16 sites in 3 countries.
16 sites in 3 countries
Belgium9 sites
Investigating site BE01
Anderlecht
Investigating site BE05
Bruges
Investigating site BE09
Brussels
Investigating site BE02
Charleroi
Investigating site BE04
Genk
Investigating site BE06
Ghent
Investigating site BE07
Hasselt
Investigating site BE08
Mons
Investigating site BE03
Ottignies
France5 sites
Investigating site FR01
Amiens
Investigating site FR04
Bordeaux
Investigating site FR06
Évry
Investigating site FR03
Paris
Investigating site FR02
Rouen
Netherlands2 sites
Investigating site NL02
Maastricht
Investigating site NL01
Rotterdam
About this study
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
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.
- Conditions
- Long Bone Non-Union
- Being tested
- PREOB® Implantation, Bone Autograft
- Keywords
- Non-Union Fractures, Impaired Healing, Fractures, Orthopedics, Bone, Musculoskeletal Disorders
- Medical subject headings
- Fractures, Bone, Musculoskeletal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PREOB® ImplantationDrug
Bone AutograftProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| PREOB® Implantation | Experimental | Each patient will undergo a single administration of PREOB® into the non-union site, under local or loco-regional anesthesia. Receives: Drug: PREOB® Implantation |
| Bone Autograft | Active comparator | Each patient will be treated by Bone Autograft according to standard-of-care procedure of the investigating site. Receives: Procedure: Bone Autograft |
What is being measured
The primary outcome is the main question the study is designed to answer.
Global Disease Evaluation as perceived by the patient using a Visual Analogue Scale
Measured: 12 months
Radiological healing progression using the RUS(T) as assessed by CT scan
Measured: 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
Measured: 12 months
Secondary outcomes (4)
Pain using a Visual Analogue Scale
Measured: 12 months
Weight-bearing using Likert Scale
Measured: 12 months
Well-being score as assessed by the SF-12 questionnaire
Measured: 12 months
Radiological improvement using the RUS(T) as assessed by X-ray
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Dec 2012 (estimated)
- Study startJun 2012
- Primary completionApr 2018
- Study completionApr 2019
Why it stopped: focus resources in the allogeneic platform and provide optimal value for patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Long Bone Non-UnionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bone Therapeutics S.A
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01756326
- Sponsor's protocol ID
- PREOB-NU3
- Status last verified
- Jun 2020
- First submitted
- 20 Dec 2012
- Last updated
- 11 Jun 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01756326
- Acronym / sponsor ID
- PREOB-NU3
- Conditions
- Long Bone Non-Union
- Keywords
- Non-Union Fractures, Impaired Healing, Fractures, Orthopedics, Bone, Musculoskeletal Disorders
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: focus resources in the allogeneic platform and provide optimal value for patients
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Bone Therapeutics S.AIndustry (pharma, biotech, devices)
- Study start
- Jun 2012
- Primary completion
- Apr 2018 (actual)
- Study completion
- Apr 2019 (actual)
- First posted
- 25 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PREOB® Implantation | Experimental | Drug: PREOB® ImplantationEach patient will undergo a single administration of PREOB® into the non-union site, under local or loco-regional anesthesia. |
| Bone Autograft | Active comparator | Procedure: Bone AutograftEach patient will be treated by Bone Autograft according to standard-of-care procedure of the investigating site. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PREOB® Implantation | Drug | PREOB® Implantation |
| Bone Autograft | Procedure or surgery | Bone Autograft |
Primary outcome
Global Disease Evaluation as perceived by the patient using a Visual Analogue Scale
Time frame: 12 months
Radiological healing progression using the RUS(T) as assessed by CT scan
Time frame: 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
Time frame: 12 months
4 secondary outcomes
Pain using a Visual Analogue Scale
Time frame: 12 months
Weight-bearing using Likert Scale
Time frame: 12 months
Well-being score as assessed by the SF-12 questionnaire
Time frame: 12 months
Radiological improvement using the RUS(T) as assessed by X-ray
Time frame: 12 months
Results and safety
The study was stopped early (reason given: focus resources in the allogeneic platform and provide optimal value for patients). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
16 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing PREOB® Implantation and Bone Autograft in people with Long Bone Non-Union, run by Bone Therapeutics S.A at 16 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Belgium, France, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: focus resources in the allogeneic platform and provide optimal value for patients). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Global Disease Evaluation as perceived by the patient using a Visual Analogue Scale (time frame: 12 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2020.