A Study Evaluating the Efficacy of a Single Injection Autologous Adipose Derived Mesenchymal Stromal Cells in Patients With Knee Osteoarthritis

Study Overview
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Brief Summary
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ASCs will be administered via intra-articular use into the knee joint affected by OA where they are expected to exert their therapeutic effects. The objective of this clinical trial is to generate efficacy and tolerability profiles of single injections of 2 dosages of autologous ASCs versus standard of care (placebo), when administered locally into a knee joint affected by OA after in vitro cell expansion. The potential of ASC to lead to a disease-modifying therapeutic option for the treatment of this chronic and debilitating disease will be assessed by MRI after 1 and 2 years. This will be a phase IIb, multi-centre, prospective, randomized, double-blind study, comparing culture-expanded autologous ASC with placebo.

Official Title
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A Phase IIb, Prospective, Multicentre, Double-blind, Triple-arm, Randomized Versus Placebo Trial, to Assess the Efficacy of a Single Injection of Either 2 or 10 x 106 Autologous Adipose Derived Mesenchymal Stromal Cells (ASC) in the Treatment of Mild to Moderate Osteoarthritis (OA) of the Knee, Active and Unresponsive to Conservative Therapy for at Least 12 Months

Conditions
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Osteoarthritis

Intervention / Treatment
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* Biological: Injection (2x106 ASC/5ml).
* Biological: Injection (10x106 ASC/5ml).
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic mild to moderate osteoarthritis (OA) of the index knee as defined by the American college of Rheumatology (ACR) Must meet pain criteria at the time of screening/baseline visit since at least half of the days in the previous month NSAID washout of at least 2 days before screening/baseline Exclusion Criteria: Previous treatments acting on cartilage or bone metabolism Received intra-articular injection of corticosteroids, platelet rich plasma or hyaluronic acid within the previous 6 months, Significant trauma or surgery to the index knee within the last year or arthroscopy of the index knee within 12 months of screening. Kellgren-Lawrence Grade 1 or 4 in the index knee on any incidences. Osteoarthritis causing significant pain in any joint other than the identified knee, i.e., pain in hip, or contralateral knee (≥ 20 mm pain) as confirmed by a separate VAS at baseline for any other painful joint concerned History of joint replacement of the knee or hip within the previous 12 months

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 75 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2x106 ASC intra-articular injection<br>Injection of Autologous adipose derived stem cells (2x106 ASC/5ml). The patient of this group will receive one single administration of the cells and will be followed for 12 months. A final follow up visit will occur at Month 24. | Biological: Injection (2x106 ASC/5ml).<br>* Injection of Autologous adipose derived stem cells (2x106 ASC/5ml). The patient of this group will receive one single administration of the cells and will be followed for 12 months. A final follow up visit will occur at Month 24.<br>|
| Experimental: 10x106 ASC intra-articular injection<br>Injection of Autologous adipose derived stem cells (10x106 ASC/5ml). The patient of this group will receive one single administration of the cells and will be followed for 12 months. A final follow up visit will occur at Month 24. | Biological: Injection (10x106 ASC/5ml).<br>* Injection of Autologous adipose derived stem cells (10x106 ASC/5ml). The patient of this group will receive one single administration of the cells and will be followed for 12 months. A final follow up visit will occur at Month 24.<br>|
| Placebo Comparator: Placebo<br>0.5% glucose in saline with 4.5% albumin | Other: Placebo<br>* Injection of placebo 0.5% glucose in saline with 4.5% alb/5ml The patient of this group will receive one single administration and will be followed for 12 months. A final follow up visit will occur at Month 24.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of pain or physical function | evaluate the efficacy of ASC in mild to moderate knee OA (KL 2-3) based on increase in the number of strict responders defined by improvements from baseline in WOMAC pain or physical function subscores 50% with absolute changes 20 mm at 6 month, compared to placebo | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disability (WOMAC) | assessed by WOMAC questionnaire | Months 1, 3, 6, 12 and 24 | 
| Disability (KOOS) | assessed by KOOS (Knee injury and Osteoarthritis Outcome Score questionnaire) | Months 1, 3, 6, 12 and 24 | 
| Disability (SAS) | assessed by SAS questionnaire (The Short Arthritis Assessment Scale) | Months 1, 3, 6, 12 and 24 | 
| Change in Quality of life | assessed by SF-36 questionnaire | Months 1, 3, 6, 12 and 24 | 
| painkillers consumption | Changes from baseline (Day 0) to months 1, 3, 6, 12 and 24 in use of painkillers | Months 1, 3, 6, 12 and 24 | 
| Structural changes (X-Ray) | Changes from baseline (Day 0) to months 12 and 24 in femorotibial joint space of the index knee on X-ray | Months 12 and 24 | 
| Structural changes (MRI) | Changes from baseline (Day 0) to months 12 and 24 by MOAKS (MRI Osteoarthritis Knee score) | Months 12 and 24 |