Autologous Osteoblastic Cells Implantation to Early Stage Osteonecrosis of the Femoral Head

Study Overview
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Brief Summary
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Non-traumatic osteonecrosis is a painful disorder of the hip characterized by a necrosis of the osteomedullary tissue, which leads to subchondral bone collapse and joint destruction. Core decompression is currently the treatment of choice for early stage osteonecrosis of the femoral head. This method consists in decompressing the rigid intra-osseous chamber to promote revascularization, thus halting progression of the disease and stimulating repair. Still this treatment remains highly controversial, since the success rates of the first studies have not been repeated. The exact pathology mechanisms involved in osteonecrosis have not yet be fully elucidated. Several hypotheses have been evoked, including fat embolism, trabecular bone microfractures, microvascular tamponade and, more recently, impaired bone and/or mesenchymal cells recruitment. Three studies have indicated the potential clinical benefits of cell-based approaches for the treatment of osteonecrosis (Hernigou 1997, Hernigou & Beaujean 2002, Gangji et al. 2004). This is on the basis of these observations that a proprietary population of autologous osteoblastic cells (PREOB®) has been developed. This Phase 2B study aims at demonstrating the efficacy and safety of PREOB® in the treatment of early stage osteonecrosis of the femoral head. The primary goal of this study was to investigate the safety and efficacy of the implantation of the investigational product PREOB® (human autologous bone marrow-derived osteoblastic cells) in comparison to bone marrow concentrate (BMC) when implanted at the osteonecrotic lesion of the femoral head, with a follow-up period of up to 5 years.

Official Title
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Treatment of Osteonecrosis of the Femoral Head by Implantation of Preosteoblastic Cells: a Randomized, Controlled, Single Blind Pilot Study

Conditions
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Avascular Necrosis of Femur Head

Intervention / Treatment
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* Drug: Core decompression/PREOB® implantation
* Drug: Core decompression/BMC implantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ARCO stage I or II non-traumatic osteonecrosis of the femoral head, confirmed by conventional X-ray and magnetic resonance imaging (MRI) of the hip Aged 18 or higher Ability to provide a written, dated and signed informed consent prior to any study-related procedure to understand and comply with study requirements Exclusion Criteria: Evidence of malignant disorder in the past five years Positive serology for hepatitis B, hepatitis C, HIV Patient unable to undergo a MRI

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Core decompression/PREOB® implantation<br>Core decompression/autologous osteoblastic cells (PREOB®) implantation | Drug: Core decompression/PREOB® implantation<br>* All subjects received a core decompression under general anesthesia combined with the implantation of PREOB® into the necrotic lesion (single administration).<br>|
| Active Comparator: Core decompression/BMC implantation<br>Core decompression/bone marrow concentrate (BMC) implantation | Drug: Core decompression/BMC implantation<br>* All subjects received a core decompression under general anesthesia combined with the implantation of BMC into the necrotic lesion (single administration).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of responder subjects | Response defined as the absence of progression to fractural stage (ARCO stage III or higher) & a clinically significant pain improvement | 24 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 |  | 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of responder subjects |  | 3, 6, 12 and 36 months | 
| Percentage of subjects progressing to fractural stage (ARCO stage III or higher), as assessed by conventional X-ray |  | 3, 6, 12, 24 and 36 months | 
| Change from baseline in VAS pain score |  | 3, 6, 12, 18, 24, 36 and 48 months | 
| Change from baseline in WOMAC® score |  | 3, 6, 12, 18, 24, 36 and 48 months | 
| Change from baseline in Lequesne score |  | 3, 6, 12, 18, 24, 36 and 48 months | 
| Proportion of subjects undergoing a total hip arthroplasty |  | 6, 12, 24 and 36 months | 
| Time to hip fracture |  | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteonecrosis, Femoral Head, Hip, Orthopedics, Bone, Musculoskeletal Disorders