Phase 2B Clinical Study of Chondrogen for Treatment of Knee Osteoarthritis

Study Overview
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Brief Summary
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Primary osteoarthritis is a debilitating disease characterized by extensive damage to the joints and excruciating pain leading to loss of activity and depression. Despite advances in diagnosis, the quest for the development of a disease-modifying osteoarthritis drug has proven unsuccessful. Human cartilage only has limited regenerative potential. Transplantation is a promising strategy given the high proliferative capacity of MSCs and their potential to differentiate into cartilage-producing cells - chondrocytes. The acquisition of MSC does not require invasive surgical intervention or cartilage extraction from other sites as required by other cell-based strategies. The investigators inject allogeneic human mesenchymal stem cells to the cartilage lesions in patients via intra-articular injection method, and to investigate the efficacy and safety.

Detailed Description
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Osteoarthritis is one of the commonest diseases in the world, with a global disease burden of 83%. Plain radiograph remained the main modality in diagnosing osteoarthritis. Chondrogen is a mesenchymal stem cell-derived from umbilical cord tissue product. The mesenchymal stem cell is used for the study because of its ability to proliferate and differentiate into various tissues such as chondrocytes, adipocytes, and osteocytes. Various clinical studies have been conducted for arthritis, orthopedic, joint, and cartilage. This study will enroll 100 patients age 30-70 years old. They will be divided into 2 groups which are the group which will receive the investigational drug (ChondrogenTM and HA) and another group will receive a placebo (saline and HA). It will be a randomized double-blinded study where the participants and the investigator would not know what are the things being received. This study will be conducted for 24 months. The injection will be given on the baseline day after screening the volunteers. The patients will be assessed on VAS, WOMAC, IKDC, KOOS PROMIS29, the interleukins, and MRI.

Official Title
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Phase 2B: Randomized Double-Blinded Clinical Study of Chondrogen for Treatment of Knee Osteoarthritis

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Biological: Chondrogen
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 30-70 years old No serious infection, chronic diseases, diabetes and tuberculosis Idiopathic or secondary osteoarthritis of the knee with grade 1-3 defined by the modified Kellgren-lawrence classification Written informed consents were obtained from all subjects. Exclusion Criteria: Pregnant or lactating women Women of childbearing potential unwilling to use two forms of contraception Cognitively impaired adults Presence of large meniscal tears Inflammatory or post-infectious arthritis More than 5 degrees of varus or valgus deformity Kellgren Lawrence grade 4 osteoarthritis in two compartments in persons over 60 years of age Intra-articular corticosteroid injection within the 3 previous months Major neurologic deficit Arthroscopy during the previous 6 months Poorly controlled diabetes mellitus Immunosuppressive or anticoagulant treatment NSAID therapy within 15 days prior to inclusion in the study Serious medical illness with a life expectancy of less than 1 year Prior admission for substance abuse Body Mass Index (BMI) of 40 kg/m2 or greater Patient receiving experimental medication or participating in another clinical study within 30 days of signing the informed consent

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: 100 patients will be selected from 2 different study sites. Each study site comprises 50 patients.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Participant of Phase 2B Clinical Study Chondrogen<br>50 participants will receive the investigational drug (Chondrogen and Hyaluronic Acid) through the intra-articular injection method. The participants will receive the investigational drug one time. The injection will be provided to the participant on the baseline day. | Biological: Chondrogen<br>* Mesenchymal stem cell-derived from umbilical cord Wharton Jelly and hyaluronic acid<br>* Other names: Mesenchymal Stem Cell;|
| Placebo Comparator: Placebo Participant of Phase 2B Clinical Study Chondrogen<br>50 participants will receive the placebo (Saline and Hyaluronic Acid) through the intra-articular injection method. The participants will receive the investigational drug one time. The injection will be provided to the participant on the baseline day. | Biological: Placebo<br>* Consist of saline and hyaluronic acid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VAS score | Change from Baseline in Visual Analogue Scale (VAS) | 12 months | 
| WOMAC score | Change from Baseline in Western Ontario and McMaster Universities Osteoarthritis Index Score (WOMAC) | 12 months | 
| IKDC score | Change from Baseline in knee function change and improvement (IKDC) | 12 months | 
| KOOS score | Change from Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PROMIS29 score | Change in Patient-Reported Outcomes Measurement Information System (PROMIS29) scores | 12 months | 
| Kellegren-Lawrence grading | Number of participants evaluated by X-ray and MRI of knee OA from baseline Kellegren-Lawrence grading system. | 12 months | 
| Interleukins | Changes of interleukins (IL-1b, IL-6, PGE-2, TGF-b, TNF-a, IGF-1) of articular cavity fluid from baseline to week 12 | 12 months |