Allogeneic Mesenchymal Stem Cells for Osteoarthritis

Study Overview
=================
Brief Summary
-----------------
This study is designed to know the safety and efficacy of 2 different doses of mesenchymal stem cells in patients suffering from osteoarthritis of knee joint.

Official Title
-----------------
A Randomized, Double Blind, Multicentric, Placebo Controlled, Phase -II Study Assessing the Safety and Efficacy of Intraarticular Ex-vivo Cultured Adult Allogeneic Mesenchymal Stem Cells in Patients With Osteoarthritis of Knee

Conditions
-----------------
Osteoarthritis of Knee Joint

Intervention / Treatment
-----------------
* Biological: Ex- vivo cultured adult allogeneic MSCs
* Biological: Plasmalyte-A


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males or females in the age 20 - 70 years (both inclusive) Radiographic evidence of grade 2 to 3 osteoarthritis based on the Kellgren and Lawrence radiographic entry criteria. History of primary idiopathic osteoarthritis of the knee characterized by pain which requires intake of analgesics. Self-reported difficulty in at least one of the following activities attributed to knee pain: lifting and carrying groceries, walking 400 metres, getting in and out of a chair, or going up and down stairs. Patients who have been on stable medication for the past three months. Patients who have not received intra articular steroids or hyaluronan within the last three months. Female patients of childbearing age must be willing to use accepted methods of contraception during the course of the study Ability to provide written informed consent. Exclusion Criteria: Prior or ongoing medical conditions (e.g., concomitant illness, psychiatric condition, alcoholism, drug abuse), medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the subject, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results. History of surgery, including arthroscopy, or major trauma to the study joint in the previous 12 months Signs of active study joint inflammation including redness, warmth, and/or, if qualifying with osteoarthritis of the knee, a large, bulging effusion of the study knee joint with the loss of normal contour of the joint at the screening visit or at the baseline examination Infections in or around the knee. Patients awaiting a replacement knee or hip joint Patients with other conditions that cause pain Significantly incapacitated or disabled and would be categorized as ACR Functional Class IV (largely or wholly incapacitated), or unable to walk without assistive devices Patients with other known rheumatic or inflammatory disease such as rheumatoid arthritis Other pathologic lesions on x-rays of knee Positive hepatitis B surface antigen, hepatitis C antibody test, Anti human immunodeficiency virus (HIV) antibody test, or VDRL History of Bleeding disorders Known hypersensitivity to Hyaluronan products or animal sera For women of child-bearing potential: positive pregnancy test or lactating

Ages Eligible for Study
-----------------
Minimum Age: 20 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: Ex- vivo cultured adult allogeneic MSCs<br>Single intraarticular dose of allogeneic MSCs | Biological: Ex- vivo cultured adult allogeneic MSCs<br>* Single intraarticular dose of allogeneic MSCs suspended in 2ml Plasmalyte followed by 2ml of Hyaluronan<br>|
| Placebo Comparator: Plasmalyte-A<br>Single intraarticular dose of 2ml Plasmalyte | Biological: Plasmalyte-A<br>* Single intraarticular dose of 2ml Plasmalyte followed by 2ml Hyaluronan<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and percentage of patients with adverse events as a measure of safety and tolerability | Safety evaluation will include assessment of physical examination, periodic monitoring of vital signs (heart rate, respiratory rate, blood pressure and temperature), clinical laboratory investigations (including haematology, serum chemistry, LFT, urine-analysis) and 12-lead ECG recording. Tolerability: Adverse events monitored using information volunteered by the patients and as observed by the PI will be summarized descriptively by total number of AE(s) and compared between the study arms. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the WOMAC OA (Western Ontario and McMaster Universities Osteoarthritis) Index -pain subscale score |  | 1 Year | 
| Change from baseline in WOMAC OA stiffness index |  | 1 Year | 
| Change from baseline in WOMAC OA composite index |  | 1 Year | 
| Change from baseline in ICOAP (Intermittent and Constant Osteoarthritis Pain) |  | 1 Year | 
| Change from baseline in radiographic (X-ray) findings of knee |  | 1 Year | 
| Change from baseline in the WORMS score of knee using MRI |  | 1 Year | 
| Change from baseline in arthritis pain scores on the visual analogue scale |  | 1 Year | 
| Reduction in the intake of analgesic tablets from baseline |  | 1 Year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Osteoarthritis, Knee, Stem cell, MSC