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