A Study to Assess Safety and Efficacy of Umbilical Cord-derived Mesenchymal Stromal Cells in Knee Osteoarthritis

Study Overview
=================
Brief Summary
-----------------
Knee-osteoarthritis (OA) is a common and disabling problem, that represents a global health issue since none of the current therapies are truly disease modifying. The use of mesenchymal stem cells (MSCs) in OA-preclinical models has been associated with a reduction in cartilage degradation, the attenuation of bone sclerosis and an effective anti-inflammatory response. Investigators have designed a randomized phase I/II placebo controlled trial of UC-MSCs in knee OA. Outcomes will be evaluated at 12 months, comparing monodosis versus double intra-articular injection, re-randomized at 6 months.

Official Title
-----------------
A Phase I/II, Randomized, Double-blind, Controlled Study to Assess Safety and Efficacy of Umbilical Cord-derived Mesenchymal Stromal Cells (UC-MSCs) in Patients With Knee Osteoarthritis

Conditions
-----------------
Osteoarthritis

Intervention / Treatment
-----------------
* Biological: umbilical-cord mesenchymal stromal cells
* Drug: Hyaluronic Acid


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Symptomatic Knee OA, Kellgren and Lawrence grade I, II, III on plain Rx films. Chondromalacia patella grade I-III on knee MRI. With or without meniscal tear. Stable knee and normal clinical exam of involved extremity Written informed consent for patients. Exclusion Criteria: Bilateral symptomatic knee OA Local or systemic infection. Active neoplasia or immunosuppressive state Pregnancy or Breastfeeding Body Mass Index ≥ 30 Presence of Pacemaker or Lower extremity metal implant Anticoagulant treatment other than aspirin. Recent use of oral (previous month) or intra-articular (previous 3 months) corticosteroids Concomitant inflammatory joint disease (cristal, connective tissue disease) Valgus (>10o) or Varus (>5o) deformity of involved extremity Condilar or Tibial plateau Generalized Bone Marrow edema on MRI Significant symptomatic hip or spine disease Significant abnormality in baseline lab tests

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Umbilical-cord mesenchymal stromal cells<br>Umbilical-cord mesenchymal stromal cells (UC-MSCs) Allogeneic UC-MSCs 20 x 10e6 diluted on 3 mL of saline solution + 5% of Plasma AB Arm 2a: single infusion group. UC-MSCs at 0 month Arm 2b: double infusion group. UC-MSCs at 0 and 6 months | Biological: umbilical-cord mesenchymal stromal cells<br>* Intra-articular knee injection of UC-MSC 20x10e6 at 0 and 6 months<br>* Other names: UC-MSCs;|
| Active Comparator: Hyaluronic Acid (HA)<br>Drug: Hyaluronic Acid 3 mL of HA intra-articular injection at baseline and 6 months | Drug: Hyaluronic Acid<br>* Intra-articular knee injection of Hyaluronic Acid (3ml) at 0 and 6 months<br>* Other names: Durolane;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who experience an adverse event | according to National Cancer Institute Common Terminology Criteria for Adverse Effects (NCI-CTCAE) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical function improvement measured by WOMAC OA index |  | 12 months | 
| Change in pain density measured by Visual analogue scale (VAS) |  | 12 months | 
| QoL improvement measured by SF-36 |  | 12 months | 
| Changes in WORMS scale measured by knee MRI |  | 12 months |