Long-Term Study of CartiPRO for Knee Pain Due to Osteoarthritis or Cartilage Damage

Inclusion Criteria

• Age 19 years and older

• Diagnosed with unilateral or bilateral knee osteoarthritis according to American College of Rheumatology (ACR) criteria, with at least 3 of the following 6 features:

• Age ≥50 years

• Morning stiffness <30 minutes

• Crepitus on active motion

• Bony tenderness

• Bony enlargement

• No palpable warmth

• Radiographic evidence of Kellgren-Lawrence grade I, II, or III osteoarthritis within 6 months prior to screening or at screening visit

• Weight-bearing pain Visual Analogue Scale (VAS) score ≥40 mm in at least one knee joint at screening

• Able to walk without assistive devices (walkers or canes), OR if using a walking aid routinely for past 6 months, able to continue using the same device throughout the study

• Able to understand and complete efficacy assessment questionnaires

• Willing and able to provide written informed consent

Exclusion Criteria

• Body Mass Index (BMI) ≥32 kg/m²

• Chronic inflammatory joint disease (e.g., rheumatoid arthritis)

• Inflammatory joint disease (e.g., septic arthritis)

• Secondary knee osteoarthritis due to ochronosis, hemochromatosis, or systemic disease

• Painful musculoskeletal conditions (e.g., Sudeck's atrophy, Paget's disease, herniated intervertebral disc)

• Polyarticular disease with severe osteoarthritis in other joints (e.g., hip) that may affect knee pain evaluation

• Radiographic evidence of definite loss of patellofemoral joint space

• Moderate to severe joint effusion confirmed by positive patellar tap test or equivalent

• History of myocardial infarction, congestive heart failure, other serious cardiac disease, or uncontrolled hypertension (≥140/90 mmHg despite treatment with ≥3 antihypertensive agents)

• History of autoimmune disease

• Active infection requiring parenteral antibiotics

• History of psychiatric disorder or epilepsy

• Cancer diagnosis within 5 years prior to screening

• Uncontrolled type 1 or type 2 diabetes mellitus (HbA1c >7%)

• Surgical procedures (including arthroscopy) on target knee within 1 year (surgery on contralateral knee or hip may be exclusionary if it could affect target knee assessment)

• Intra-articular corticosteroid injection into target knee within 12 weeks

• Systemic corticosteroid use within 4 weeks (topical and inhaled corticosteroids permitted)

• Surgery or radiation therapy to knee joint within 12 weeks, or not fully recovered from side effects

• Immunosuppressive therapy (e.g., Cyclosporine A, Azathioprine) within 6 weeks

• Intra-articular injections (e.g., hyaluronic acid) into knee joint within 6 months

• Prohibited concomitant medications within 2 weeks (unless washout period is adequate)

• Anticoagulants (e.g., warfarin, NOACs), antiplatelet agents (e.g., aspirin >100 mg/day, clopidogrel; low-dose aspirin ≤100 mg/day permitted), thrombolytic agents (e.g., urokinase, alteplase), or Vitamin E >1000 IU/day within 2 weeks (unless adequate washout)

• Habitual use (≥3 months) of psychoactive drugs or narcotic analgesics that may affect pain perception

• History of cell therapy or gene therapy to target joint

• Planned cell therapy or gene therapy to target joint

• Abnormal laboratory values at screening:

• ALT, AST, BUN, or serum creatinine >2× upper limit of normal

• Engaged in high-intensity aerobic or heavy anaerobic exercise that may affect the knee joint

• Dermatological disease at injection site or site deemed unsuitable for injection

• Ligament instability of Grade II or higher in target knee (Grade 0: none; Grade I: 0-5 mm; Grade II: 5-10 mm; Grade III: >10 mm)

• Known hypersensitivity to investigational product or its components

• Pregnant or breastfeeding women

• Women or men of childbearing potential unwilling to use acceptable contraception during study (acceptable methods: intrauterine device, tubal ligation, sterilization surgery, condom or diaphragm with spermicide, natural family planning)

• Participation in another clinical trial within 4 weeks

• Cognitive impairment or dementia preventing informed consent

• Any other condition that makes the subject unsuitable for study participation per investigator judgment