Phase IIb/III on the Efficacy and Safety of Autologous Osteoblastic Cells (PREOB®) Implantation in Non-infected Hypotrophic Non-union Fractures
This study is currently recruiting participants.
Verified December 2012 by Bone Therapeutics S.A
Sponsor:
Bone Therapeutics S.A
Information provided by (Responsible Party):
Bone Therapeutics S.A
ClinicalTrials.gov Identifier:
NCT01756326
First received: December 20, 2012
Last updated: December 24, 2012
Last verified: December 2012
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Purpose
Non-union fracture is a bone disorder characterised by a failure of the fracture to heal within 6 to 9 months after onset. The normal time for fracture healing is to 4 months. Possible causes for non-union fracture 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 osteoblastic cells to multiply. Currently, the most common treatment is an invasive surgery, performed under general anaesthesia, during which a piece of bone is harvested from the patient pelvis to be reimplanted directly at the site of the non-union fracture. This treatment, also known as an autologous bone graft, produces good results but requires major surgery of several hours under general anaesthesia, followed by about 4 to 5 days of hospitalization. Severe complications have been reported in more than 20% of patients.
The present phase III study aims at demonstrating the efficacy and safety 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 Conservative Treatment in a superiority design during the first part of the study and to Bone Autograft in a non-inferiority design during the second part of the study.
| Condition | Intervention | Phase |
|---|---|---|
|
Pseudarthrosis Non-Union Non-Union Fracture Fracture Musculoskeletal Disorder Bone Disease |
Drug: Core Biopsy/PREOB® Implantation Procedure: Bone Autograft Other: Conservative Treatment |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | 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. |
Resource links provided by NLM:
Further study details as provided by Bone Therapeutics S.A:
Primary Outcome Measures:
- Global patient evaluation as perceived by the patients using a visual analogue scale [ Time Frame: at 12 months first study part (PREOB® vs. Conservative Treatment) and at 9 months second study part (PREOB® vs. Bone Autograft) ] [ Designated as safety issue: No ]Visual Analogue Scale (Global Health status)
- Radiological healing progression using the RUS(T) as assessed by CT scan [ Time Frame: at 12 months first study part (PREOB® vs. Conservative Treatment) and at 9 months second study part (PREOB® vs. Bone Autograft) ] [ Designated as safety issue: No ]RUST score
- Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Screening, pretreatment visits, D0,1,3,6,9,and 12 months first study part (PREOB® vs. Conservative Treatment) and Day 0, 1, 3, 6, 9 months second study part (PREOB® vs. Bone Autograft) and at 24 and 36 months for the long term study follow-up ] [ Designated as safety issue: No ]During the whole study, subjects will be systematically assessed for the potential occurence of any AE or SAE, related to the product or related to the procedure, using patient open questionnaire, physical examination (including body mass index and vital signs), and laboratory measurements
Secondary Outcome Measures:
- Pain (VAS)- Weight bearing (Likert scale) - Well-being (SF12) - Global disease (VAS) by physician [ Time Frame: at 12 months first study part (PREOB® vs. Conservative Treatment) and at 9 months second study part (PREOB® vs. Bone Autograft) ] [ Designated as safety issue: No ]
- Pain using visual analogue scale
- Weight-bearing using a Likert scale
- Well-being score as assessed by SF 12
- Global disease evaluation as perceived by the physician using a visual analogue scale
- Radiological improvements using the RUS(T) as assessed by X-Ray
| Estimated Enrollment: | 210 |
| Study Start Date: | June 2012 |
| Estimated Study Completion Date: | September 2017 |
| Estimated Primary Completion Date: | September 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Core biopsy/PREOB® Implantation
All PREOB®-treated patients will undergo a core biopsy (5-mm trephine) under local or loco-regional anaesthesia combined with the implantation of PREOB® into the non-union site. The volume of PREOB® to be injected will vary depending on the size of the non-union interline (from 2 ml to 4 ml at a concentration of 4.106 cells/ml).
|
Drug: Core Biopsy/PREOB® Implantation Other: Conservative Treatment |
|
Conservative Treatment
All Conservative-treated patients will be treated by calcium and cholecalciferol (daily dose of ~500 mg and ~800 IU respectively) until the end of their follow-up (patients undergoing a PREOB® implantation will also be treated by calcium and cholecalciferol).
|
Other: Conservative Treatment |
|
Bone Autograft
All patients who will have failed under Conservative Treatment or PREOB® implantation will be treated by Bone Autograft according to standard-of-care procedure of the investigating site.
|
Procedure: Bone Autograft |
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Patient diagnosed with a non-infected hypotrophic (atrophic and oligotrophic) non-union fracture of a long bone which will be of a minimum 6 months without signs of evolution over the last 3 months at the time of randomisation/baseline
- Patient aged 18 to 65 years inclusive
- Patient capable to understand and comply with study requirements
- Patient capable to provide a written, dated, and signed informed consent prior to any study procedure for participation in the study and transmission of personal "anonymized" data.
- Normal haematology function
Female patients must be:
- Post-menopausal (defined as at least 12 month post-cessation of menses),or surgically sterile, or
- For women with childbearing potential, using reliable contraceptive method for at least 6 weeks prior to screening and during the whole study period.
Exclusion Criteria:
- Non-union interline > 1 cm
- Insufficient fracture stability
- Osteosynthesis material revision performed less than 3 months from the randomization/baseline visit for simple revision without surgery or bone graft at the non-union site or less than 6 months from the randomization/baseline visit for revision with surgery or bone graft at the non-union site.
- Osteosynthesis materials at the non-union site other than intramedullary nails or plates.
- Open fracture with septic local infection and/or abnormal CRP and/or abnormal skin and scar
- Bone infection at site
- Femoral neck fracture
- Multifocal fracture/non-unions
- Non-union or non-consolidated fracture on the neighbouring bone
- RUS(T) > 8 as assessed by conventional CT scan
- Global disease evaluation as assessed by the patient < 20 mm on a visual evaluation scale
- Nerve damage and/or neuropathic/neuropathic-like pain at non-union fracture site
- Tendon lesion (rupture or enthesopathy) at non-union fracture site
- Positive serology for hepatitis B, hepatitis C, HIV, HTLV-1 and syphilis
- Presence, or previous history, of risks factors for diseases caused by prions, including patients diagnosed with Creutzfeldt-Jakob disease, or variant Creutzfeldt-Jakob disease, or having a family history of noniatrogenic Creutzfeldt-Jakob disease; patients with a history of rapid progressive dementia or degenerative neurological disease; recipients of hormones derived from the human pituitary gland; and recipients of grafts of cornea, sclera, and dura mera
- Global sepsis
- Haemoglobin level <10 g/dl
- Renal and hepatic impairment
- Poorly controlled diabetes mellitus
- Clinically relevant abnormal ECG at screening
- Known history of severe acute or chronic allergy requiring medical therapy
- Current or past history of solid or haematological neoplasia or bone marrow transplantation
- Life expectancy less than 6 months
- Current medical disease that could interfere with the evaluation of efficacy.
- Known severe osteoporosis
- Current (or within 6 months of screening) illicit drug abuse
- Current or past treatment for cancer or blood dyscrasia, including any chemotherapy, radiotherapy, immunotherapy, biotherapy, haematopoietic growth factors, anti-vasculogenesis, and/or antiangiogenesis treatment
- Current (or within 1 month of screening) anticoagulants, including intravenous, intramuscular, subcutaneous, and oral anticoagulation at any therapeutic dosage (but not prophylactic use)
- Current or past intravenous bisphosphonate therapy
- Current (or within 6 months of screening) oral bisphosphonate therapy
- Current (or within 1 month of screening) treatment with calcitonin, raloxifen, teriparatide, and/or strontium ralenate
- Patients unable to undergo general anaesthesia
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01756326
Contacts
| Contact: Enrico Bastianelli, MD | 003225295990 | preob.nu3@bonetherapeutics.com |
| Contact: Jean-Louis Marques, BSc | 003225295990 | jean-louis.marques@bonetherapeutics.com |
Locations
| Belgium | |
| Clinique Saint Pierre | Not yet recruiting |
| Ottignies, Brabant Walon, Belgium, 1340 | |
| Contact: Bruno Vincent, MD | |
| Principal Investigator: Bruno Vincent, MD | |
| CHU Charleroi | Recruiting |
| Charleroi, Hainaut, Belgium, 6000 | |
| Contact: Olivier Delahaut, MD | |
| Principal Investigator: Olivier Delahaut, MD | |
| AZ St Jan | Not yet recruiting |
| Brugge, Belgium, 8000 | |
| Contact: Jan Van Meirhaeghe, MD | |
| Principal Investigator: Jan Van Meirhaeghe, MD | |
| IRIS SUD | Not yet recruiting |
| Brussels, Belgium, 1190 | |
| Contact: Marek Szpalski, MD | |
| Principal Investigator: Marek Szpalski, MD | |
| CUB-ULB Hopital Erasme | Not yet recruiting |
| Bruxelles, Belgium, 1070 | |
| Contact: Marc Jayankura, MD | |
| Principal Investigator: Marc Jayankura, MD | |
| AZ Maria Middelares | Not yet recruiting |
| Gentbrugge, Belgium, 9050 | |
| Contact: Stefan Desmyter, MD | |
| Principal Investigator: Stefan Desmyter, MD | |
| CHU Ambroise Paré | Recruiting |
| Mons, Belgium, 7000 | |
| Contact: Nathalie Busiau, MD | |
| Principal Investigator: Nathalie Busiau, MD | |
Sponsors and Collaborators
Bone Therapeutics S.A
Investigators
| Principal Investigator: | Marc Jayankura, MD | CUB-ULB Hopital Erasme |
More Information
No publications provided
| Responsible Party: | Bone Therapeutics S.A |
| ClinicalTrials.gov Identifier: | NCT01756326 History of Changes |
| Other Study ID Numbers: | PREOB-NU3 |
| Study First Received: | December 20, 2012 |
| Last Updated: | December 24, 2012 |
| Health Authority: | Belgium: Federal Agency for Medicinal Products and Health Products |
Additional relevant MeSH terms:
|
Bone Diseases Fractures, Bone Fractures, Ununited |
Musculoskeletal Diseases Pseudarthrosis Wounds and Injuries |
ClinicalTrials.gov processed this record on June 18, 2013