Phase 1/2a Study on Allogeneic Osteoblastic Cells Implantation in Delayed-Union Fractures

Study Overview
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Brief Summary
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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. There is for now no universally accepted approach to evaluate the progression of fracture healing. Typically, a fracture is considered as a delayed-union when the bone has not united within a period of time that would be considered adequate for bone healing. Delayed-union suggests that union is slow but will eventually occur without additional surgical or non-surgical intervention, whereas non-union is defined as the cessation of all reparative process of healing. The incidence of impaired healing is estimated to range from 5 to 10% of all long bone fractures, depending on the fracture site, the type and degree of injury, among other factors. Currently the treatment of choice remains bone allograft or autograft. This procedure shows in general good results but requires an invasive surgery of several hours under general anesthesia, followed by a few days of hospitalization. Because of this, major complications have been reported in up to 20-30% of patients. The present Phase 1/2a study aims at demonstrating the safety and efficacy of ALLOB®, a proprietary population of allogeneic osteoblastic cells, in the treatment of delayed-union fractures of long bones. In this study, delayed-union is defined at the time of screening as an absence of healing of minimum 3 months and maximum 7 months (+/- 2 weeks) after the onset of the fracture.

Official Title
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A Pilot Phase 1/2a, Multicentre, Open Proof-of-concept Study on the Efficacy and Safety of Allogeneic Osteoblastic Cells (ALLOB®) Implantation in Non-infected Delayed-Union Fractures

Conditions
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Long Bone Delayed-Union Fracture

Intervention / Treatment
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* Drug: ALLOB® implantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient (or patient's legally acceptable representative) capable to provide a written, dated, and signed informed consent prior to any study related procedure Non-infected delayed-union fracture of a long bone of minimum 3 months and maximum 7 months (+/- 2 weeks) Exclusion Criteria: Fracture interline larger than 2.5 cm Insufficient fracture stability Multifocal fracture Positive serology for hepatitis B, hepatitis C, Human Immunodeficiency Virus (HIV) Current or past medical disease that could interfere with the evaluation of the safety and efficacy, as judged by the investigator Severe renal or hepatic impairment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALLOB® Implantation<br>One arm: ALLOB® Implantation | Drug: ALLOB® implantation<br>* Each patient will undergo a single administration of ALLOB® into the delayed-union site under anesthesia.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Responders at 6 Months (Efficacy of ALLOB) | The success of the study will be based on the percentage of treated patients (ALLOB®) not failing under treatment. A patient will be considered as failed under treatment if, at Month 6: - He/she had a rescue surgery Or - The Global Disease Evaluation score (VAS) as perceived by the patient has not improved by at least 25% and the Tomographic Union Score (TUS) as assessed by CT scan has not increased by at least two points (versus baseline). | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Delayed-Union Fractures, Impaired Healing, Fractures, Orthopedics, Bone, Musculoskeletal Disorders