Mesenchymal Stromal Cells for the Treatment of Non-union Fractures of Long Bones

Study Overview
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Brief Summary
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The present study evaluates the effect of XCEL-MT-OSTEO-ALPHA in non-union fractures (pseudoarthrosis) of long bones in comparison to the standard treatment of autologous iliac crest. XCEL-MT-OSTEO-ALPHA is a tissue engineering product composed by ex-vivo expanded autologous mesenchymal stromal cells fixed in allogenic bone tissue, produced by Xcelia (Blood and Tissue Bank of Catalonia). The working hypothesis proposes that the tissue engineering is a valid and useful technique to achieve bone regeneration up to consolidation of non-union fractures.

Detailed Description
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A phase IIa, single center, prospective, randomized, parallel, two-arms, single-dose, open-label with blinded assessor pilot clinical trial to assess ex vivo expanded adult autologous mesenchymal stromal cells fixed in allogeneic bone tissue (XCEL-MT-OSTEO-ALPHA) in non hypertrophic pseudoarthrosis of long bones.

Official Title
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A Phase IIa, Single Center, Prospective, Randomized, Parallel, Two-arms, Single-dose, Open-label With Blinded Assessor Pilot Clinical Trial to Assess ex Vivo Expanded Adult Autologous Mesenchymal Stromal Cells Fixed in Allogeneic Bone Tissue (XCEL-MT-OSTEO-ALPHA) in Non Hypertrophic Pseudoarthrosis of Long Bones

Conditions
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Atrophic Nonunion of Fracture

Intervention / Treatment
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* Drug: XCEL-MT-OSTEO-ALPHA
* Other: autologous iliac crest
* Procedure: Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 85 years of age (male and female) Atrophic or hypotrophic metaphyseal-diaphyseal pseudarthrosis of long bones, confirmed radiographically. Signed Informed Consent Form The patient is able to understand the nature of the study Exclusion Criteria: Suspicious of pseudarthrosis focus infection diagnosed by clinical inspection and blood analysis. Positive serology for HIV (Anti-HIV I/II-Ac), Hepatitis B (HBsAg, HBcAc), Hepatitis C (Anti-HCV-Ac) or Syphilis Lúes (TP-Ac). Significant abnormal laboratory tests that contraindicates patient's participation in the study. Pregnant woman or without proper anticonceptive measures according to the investigator, or breath feeding Smoker of more than 15 cigarettes a day Congenital disorders of bones (hypophosphatemia), bone metabolic disorders associated to primary or secondary hypoparathyroidism. Badly managed diabetes mellitus. Patients diagnosed with peripheral arterial disorders Previous therapeutic radiation (5 previous years) of the affected bone. Neoplasia within the previous 5 years, or without remission The patient is legally dependent Participation in another clinical trial or treated with an investigational medicinal product the previous 30 days Other pathologic conditions or circumstances that difficult participation in the study according to medical criteria The patient does not accept to be followed-up for a period that could exceed the clinical trial length

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: XCEL-MT-OSTEO-ALPHA and surgery<br>ex-vivo expanded autologous mesenchymal stromal cells fixed in allogenic bone tissue | Drug: XCEL-MT-OSTEO-ALPHA<br>* ex-vivo expanded autologous mesenchymal stromal cells fixed in allogenic bone tissue in association with open surgery<br>Procedure: Surgery<br>* Standard surgery for non-union fractures<br>|
| Other: Autologous iliac crest and surgery<br>Standard treatment | Other: autologous iliac crest<br>* Autologous iliac crest in association with surgery<br>Procedure: Surgery<br>* Standard surgery for non-union fractures<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy assessment of XCEL-MT-OSTEO-ALPHA in non-union fractures by imaging procedures | Hounsfield units quantification by tomography in both treatment arms | 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessment of XCEL-MT-OSTEO-ALPHA in non-union fractures | Safety will be assessed by collecting adverse events throughout the experimental phase which includes a follow-up of 12 month. | 12 month | 
| Efficacy assessment of XCEL-MT-OSTEO-ALPHA in non-union fractures by imaging procedures | Characteristics of the callus by tomography and Characteristics of the callus by standard x-ray in both treatment arms | 6 month | 
| Efficacy assessment by quality of life test | Quality of life will be measured by EUROQOL-5D test | 12 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nonunion fracture, Long bones, Pseudoarthrosis, Cell therapy, Tissue engineering, Mesenchymal stromal cells