A Phase 3 Study to Evaluate the Efficacy and Safety of JointStem in Treatment of Osteoarthritis

Multi-center, Randomized, Double-Blind, Placebo Controlled Phase 3 Clinical Trial to Evaluate Efficacy and Safty of Mesenchymal Stem Cells JointStem in Patients With Knee Osteoarthritis

The purpose of this study is to investigate the efficacy and safety of autologous Adipose Tissue derived Mesenchymal stem cells (JOINTSTEM®) in patient with severe Knee Osteoarthritis.

JOINTSTEM is injectables for an OA treatment that uses autologous adipose-derived mesenchymal stem cells. As it does not use allogenic tissues and is cultured without additional genetic modification, it is classified as 'autologous cell therapy' and is completely free of immunologic rejection.

It primarily aims to improve joint function. The intra-articular injection of JOINTSTEM is expected to stimulate the regeneration of cartilage, and to innovatively improve joint function with cartilage regeneration.

The subjects of this therapy were patients with K&L grade 3 aged 20 or older.

This study is a double-blind, randomized, placebo controlled study with two arms to evaluate JOINTSTEM as a treatment for subjects with osteoarthritis. Following a 2-week screening period, approximately 260 patients will be randomly assigned into one of the following two arms in a 1:1 ratio (1 JointStem : 1 placebo control). After each patient completes 6-month visit (Visit 5) and the data management team confirms all data have no issue, the individual database will be locked and the blinding will be open for the statistical analysis.

Inclusion Criteria:

1. Age 20 and older, male and female

2. Patients must consent in writing to participate in the study by signing and dating an informed consent document

3. Diagnosis of degenerative arthritis of class 1-3 by ACR(American College of Rheumatology Criteria) Global functional criteria

4. Diagnosis of Kellgren and Lawrence grade 3 by radiographic criteria

5. Patients suitable for one of three conditions of 'diagnostic criteria for osteoarthritis of knee' based on ACR guideline

   • clinical and inspectional opinion
   • clinical and radiographic opinion
   • clinical opinion

6. Patients who has joint pain ≥ 50mm on 100mm VAS (Visual Analog Scale) at Screening

7. Patient who has WOMAC score ≥ 1000 at Screening

8. No improvement with persisting knee pain at least for 12 weeks (3 months) by nonoperational therapy before Screening

Exclusion Criteria:

1. Patients who have pregnancy plans within this trial period or childbearing age patients who do not agree to maintain contraception status through appropriate contraception methods

   • Appropriate contraception method: Use of condom, contraceptive sponges, foam, diaphragm, intrauterine device etc.
   • Periodic abstinence(e.g. methods of predicting ovulation) and moderation are not considered as appropriate contraception method.
   • Not allowed to use hormonal contraceptives
   • Childbearing age female patients, exclude menopausal female (amenorrhea for more than 24 months after the last menstruation) or female who has no possibility of pregnency by surgical sterilization operation, can participate in this study only determined negative in pregnancy test

2. Pregnant women or lactating mothers

3. Patients with Body Mass Index (BMI) > 35

4. Patients with positive human immunodeficiency (HIV), hepatitis B (HBV), hepatitis C (HCV), syphilis at screening indicative of current of pass infection

5. Patients with other disease including

   • Septic arthritis, Rheumatoid or Inflammatory joint disease, Gout, Reccurent pseudogout, Paget disease, Articular fractures, Ochronosis, Acromegaly, Hemochromatosis, Wilson's disease,Osteochondromatosis, Hereditary disorder, Genetic disorder of collagen

6. Patients who are diagnosed with malignant tumor in the past or present

7. Patients who have clinically significant diseases including

   • Cardiac disorder (Myocardial infarction, Coronary artery bypass graft, Arrhythmia and other severe Cardiac disorder etc.)
   • Resistant hypertension (systolic blood pressure > 160mmHg or diastolic pressure > 100mmHg at Screening)
   • Kidney disease (Chronic renal failure, Glomerulonephritis etc.)
   • Liver disease (Hepatocirrhosis, Fatty liver, acute or chronic liver disease etc.)
   • Endocrinopathy (Thyroiditis, Diabetes insipidus, Cushing disease etc.)

8. Patients who have significant lab abnormalities

9. Patients who have severe pain in other areas that can affect the judgement of knee joint symptom

10. Patients who underwent any arthroscopic surgery on the injection site within 6 months of the screening visit date, or scheduled to perform any surgery during the clinical trial period

11. Patients who received any drug by intra-articular injection(hyaluronic acid or steroid etc.) for treatment within 6 months prior to Screening

12. Patients who experienced as stem cell therapy or blood product injection(PRP, Prolo injection etc.)

13. Patients who received treatment within 14 days prior to Screening including(But, patients who had wash-out-period can participate in this study)

    • Take medicines including composition of Glucosamine, Chondretin sulphate and Diacerhein etc.
    • Take phytotherapeutic agent or Chinese medicine for osteoarthritis
    • Take antiinflammatory analgesic drug, NSAIDs (prescription/nonprescription pharmaceuticals) etc. (Patients who have 3 days of wash-out-period after they took acetaminophen can participate in the study)
    • Take oral steroids
    • Physical therapy or Chinese medical treatment(cupping, acupuncture, moxibustion etc.)

14. Patients with penicillin hypersensitivity reactions

15. Patients with skin diseases or infections in the area of the injection site

16. Patients who have abnormal flail over grade 2 flail knee test of anterior to posterior and varus/valgus lesion at physical examination

17. Patients who have difficulty in taking MRI because of metal materials (cardiac pacemaker or clip of cerebral artery etc.) in their body or claustrophobia -but, patients with metal materials that are not affected by magnetic field can participate in this study

18. Patients who have difficulty in liposuction or local anesthesia

19. Patients who have alcohol, drug abuse history

20. Patients who have severe neurologic and psychiatric disorders that affect clinical trials

21. Patients who had participated in other clinical trials within 12 weeks prior to this study

22. Patients who the principal investigator considers inappropriate for the clinical trial due to any other reasons than those listed above