Clinical Trial to Evaluate Efficacy and Safety of SMUP-IA-01 in Patients With Knee Osteoarthritis

Inclusion Criteria:

1. Patients who are ≥ 19 years of age on the date on which the consent form was signed

2. Patients diagnosed with knee osteoarthritis in at least one knee according to theclinical and radiological definition criteria of American College of Rheumatology (ACR) guidline at screening visit

3. Patients with knee OA corresponding to K&L Grade 2 or 3 on radiographic examinationat screening visit

4. Patients with less than 35 of BMI at screening visit

5. Patients who voluntarily decide to participate and sign the consent form

6. Patients who have persistent symptoms despite having undergone a reasonable trial ofstandard therapy (i.e., for a minimum of 3 months)

Exclusion Criteria:

1. Patients with any of the following diseases.

• infectious arthritis, autoimmune or inflammatory joint diseases, gout,recurrent pseudogout, Paget's disease, intra-articular displaced fracture,ochronosis, acromegaly, haemochromatosis, Wilson's disease, genetic disease (hyperkinesia etc.), genetic collagen disorder, etc.

2. Patients who have ever undergone surgery or radiotherapy in the knee joint areawithin the 12 weeks prior to the screening visit date, or who have not beenrecovered from its side effect yet.

3. Patients with SIF (Subchondral insufficiency fracture) corresponding to type II ofthe RPOA (rapidly progressive osteoarthritis).

4. Patients whose physical examination results show severe degree of ligamentinstability.

5. Patients who have ever been given any intraarticular drug injection (i.e.,hyaluronic acid injection, etc.) in to-be-treated (index) knee within the 6 months,prior to the screening visit date.

6. Patients who have ever been given steroids via intraarticular injection into-be-treated (index) knee within the 12 weeks prior to the screening visit date.

7. Patients who have ever taken medications or given therapy below within the past 2weeks on the basis of screening visit date. However, if patients have 14 days ofwash-out period, the patient is allowed to participate.

• drugs containing the ingredient of glucosamine, chondroitin sulfate, ordiacerein

• drugs containing herbal ingredient or herbal drugs for knee OA pain relief

• anti-inflammatory analgesics or NSAIDs (prescription/non-prescription drugs). (However, patients who take acetaminophen and have 3 days of wash-out periodare allowed to participate.)

• oral steroids

• hospital physiotherpy or oriental medicine treatment (buhang, acupunture,moxibustion etc.)

8. Patients who have skin disease on injection site or who are judged inappropriate forintra-articular injection on to-be-treated knee.

9. Patients who are judged unsuitable for MRI scanning (3.0 Tesla or higher) due to aninsertion of metal material (i.e., heart pacemaker, cerebral aneurysm clip, etc.) orobstructive phobia. However, patients who have an insertion of metal material thatis not affected by the magnetic field is allowed to participate

10. Patients with clinically significant past or present illness as follows;

• heart diseases (i.e., myocardial infarction, coronary artery bypass surgery,arrhythmia and other serious heart diseases, etc.)

• uncontrolled hypertension (not controlled down to 140/90 mmHg or below evenafter treatment with 3 or more antihypertensive drugs)

• kidney disease (i.e., chronic kidney failure, glomerulonephritis, etc.)

• liver disease (i.e., acute or chronic liver disease such as cirrhosis, fattyliver, etc.)

• endocrine diseases (i.e., thyroiditis, diabetes insipidus, Cushing's disease,etc.)

• other serious systemic diseases

11. Patient with ongoing autoimmune disorder that requires treatment with animmunosuppressive medication

12. Patients with infection that requires administration of parenteral antibiotics

13. Patients with a history of mental illness or epilepsy

14. Patients who have been diagnosed with cancer within the 5 years prior to thescreening visit date

15. Patients who have been given immunosuppressive drugs such as cyclosporin A orazathioprine within the 6 weeks prior to the screening visit

16. Patients with a history of allergic reactions to hyaluronic acid injections,cryoprotectant (dimethyl sulfoxide, DMSO), or gentamicin.

17. Patients who are pregnant or lactating, or patients who have a plan to becomepregnant during the study period

18. Male or female patients who do not agree to avoid pregnancy or the use ofappropriate contraceptive methods during the study period. But women who have giveninfertility surgery or who have passed menopause one year or more are allowed toparticipate without the consent for contraception.

19. Patients who have been given any other cell therapy products or who plan to do soduring the study period.

20. Patients who have been given any other investigational products including devicewithin the 3 months prior to the screening visit date.

21. Patients who are judged by the investigator as inappropriate for enrollment into thestudy, for any reasons other than the reasons specified above.