Ready-to-use Intra-articular Formulation of Mesenchymal Stromal Cells

Study Overview
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Brief Summary
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The goal of this clinical trial is to compare a newly developed off-the-shelf cryopreserved ready to inject Mesenchymal Stem Cell (MSC) product with the usual MSC preparation the investigators have used in knee osteoarthritis (OA) patients. Since usual MSC therapy requires cell manipulation in GMP (Good Manufacturing Practices)-type facilities, this new formulation would enable wider access to Cell therapy and Multicentric clinical trials in areas devoid of expensive facilities and equipment.

Detailed Description
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This is a double blind randomized controlled trial testing a modified formulation of an allogenic Umbilical cord (UC) derived MSC therapy that the investigators have used in a prior published clinical trial. It has been modified and characterized according to the standards of quality control that are required for the development an off-the-shelf cryopreserved MSCs product. This so called ready to inject MSC preparation will be compared with the usual MSC formulation that requires centrifugation and resuspension in different media, thus requiring access to advanced (GMP-type) facilities. A total of 60 symptomatic knee OA patients will be randomized (1.1 ratio) to receive one or the other MSC product at baseline and month 6, to be followed blindly for 12 months with baseline and end of study knee MRI imaging. The primary endpoint of the trial will be the safety according to the occurrence of adverse events (AEs) as coded by the Common Terminology Criteria for Adverse Event classification. The secondary endpoint will be efficacy, as assessed by the following validated clinical outcome measures: Western Ontario and Mc Master Universities Arthritis Index (WOMAC) Spanish validated version, Pain Visual Analog scale (VAS), Quality of life by the Short-form 36 (SF-36) questionnaire, Patient Global Assessment, and the Outcome Measures in Rheumatology Committee (OMERACT)-Osteoarthritis Research Society International (OARSI) Responder Index Criteria. Baseline MRI will be performed mainly to exclude meniscal lesions associated with accelerated knee OA. Final (12 month) MRI will be performed to assess structural change in response to treatment The completion of this project represents a main technological advance, eventually leading to the scalability and enhanced quality control of a much needed treatment, within reasonable costs and logistics, and in particular, with no need of a GMP facility at the point of care or of clinical testing

Official Title
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Enabling Advanced Medical Therapy in the Americas: A Pilot Study to Validate a Ready-to-use Intra-articular Formulation of Mesenchymal Stromal Cells, Aiming Toward an Effective and Scalable Treatment for Symptomatic Knee Osteoarthritis

Conditions
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Osteo Arthritis Knee

Intervention / Treatment
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* Biological: Ready to inject Umbilical cord-derived Mesenchymal Stromal Cell (MSC) product
* Biological: Resuspended Umbilical cord-derived Mesenchymal Stromal Cell (MSC) product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic knee OA defined by grade 1-3 Kellgren-Lawrence radiographic changes in the targeted knee. Daily pain at the affected joint for at least 3 months before inclusion Exclusion Criteria: Bilateral symptomatic knee OA (only if the contralateral knee has more severe disease) Meniscal rupture. Condylar or tibial plateau generalized bone marrow edema on MRI Major axial deviation defined by valgus (>10°) or varus (5°) deformity of the involved leg Use of oral or intra-articular steroids or hyaluronic acid in the past 6 months Ipsilateral hip or ankle pain, local or systemic infection Any form of secondary arthritis, previous malignancy, or body mass index ≥30.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 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
Interventional Model Description: Prospective Double blind Randomized Controlled Trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ready to inject MSC product<br>Cryopreserved ready to inject Umbilical Cord (UC) derived MSC | Biological: Ready to inject Umbilical cord-derived Mesenchymal Stromal Cell (MSC) product<br>* Cryopreserved thaw & inject MSC intra-articular therapy<br>* Other names: Cryopreserved Ready to inject MSC product;|
| Active Comparator: Resuspended MSC product<br>Umbilical Cord (UC) derived MSC in suspension media | Biological: Resuspended Umbilical cord-derived Mesenchymal Stromal Cell (MSC) product<br>* Cryopreserved resuspended MSC intra-articular therapy<br>* Other names: Cryopreserved resuspended MSC product;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety monitoring for Adverse events | Adverse events (AEs) reported for each study group as coded by the Common Terminology Criteria for Adverse Event classification. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WOMAC scale | Western Ontario and Mc Master Universities Arthritis Index (WOMAC) Spanish validated version. Scale ranges from 0-240 with higher scores indicating worsened state | 12 months | 
| Pain Visual Analog Scale (VAS) | VAS scale for pain, ranging from 0-10 with higher scores indicating worsened state | 12 months | 
| Quality of Life SF-36 questionnaire | Short-form 36 (SF-36) questionnaire, ranging from 0-100 with higher scores indicating better health status | 12 months | 
| Responder status | Assessed by the Outcome Measures in Rheumatology Committee (OMERACT)-Osteoarthritis Research Society International (OARSI) Responder Index Criteria. Responder status requires fulfilling at least 50% improvement in pain or function with absolute change of at least 20; or at least 20% improvemente in pain, function or patient´s global assessment, with absolute change of at least 20. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis, Degenerative joint disease, Cell therapy, Advanced Medicinal Therapy Product, Mesenchymal Stromal Cell, Mesenchymal Stem Cell, Cryopreserved cell therapy