Phase III Study on the Safety and Efficacy of a Single Intra-articular Administration of JTA-004 in Symptomatic Knee Osteoarthritis

Exclusion Criteria

• •1. History of trauma or surgery or arthroscopy at the target knee within 12 months before inclusion
• •2. Concomitant inflammatory disease or other conditions affecting the joints (e.g., infectious arthritis, rheumatoid arthritis, psoriatic arthritis or spondyloarthropathy, Paget's disease, hemochromatosis…)
• •3. Any target knee abnormality that could impact safety or efficacy assessment
• •4. Microcrystalline arthropathies: chondrocalcinosis/calcium pyrophosphate dihydrate disease (pseudo-gout) or gout if believed likely to interfere with the study endpoints, in the opinion of the Investigator
• •5. Clinically significant valgus/varus deformities at the Investigator's discretion
• •6. Any musculoskeletal condition (such as symptomatic hip OA, amputation, neurologic disorder, chronic back pain with or without radiculopathy, sciatica) that would impede measurement of efficacy at target knee
• •7. Contralateral knee pain equal to or exceeding the pain in the target knee (on the WOMAC® VA3.1 pain questionnaire) at screening and/or baseline
• •8. Knee arthroplasty planned within 12 months after the screening visit Current or previous diagnoses, signs and/or symptoms
• •9. Uncontrolled diabetes mellitus (hemoglobin A1c \[HbA1c\] \> 10% or \> 86 mmol/mol), end-stage hepatic or renal disease (severe and clinically significant abnormalities according to local laboratory ranges) documented in the subject's file
• •10. Any relevant cardiovascular disease (severe coronary insufficiency, conduction disturbances, recent myocardial infarction, cerebrovascular disease) or any clinically significant electrocardiogram (ECG) abnormality as judged by the Investigator
• •11. Subject with neuropathic pain or chronic pain syndrome including fibromyalgia
• •12. Current (or within the last 5 years prior to entering the study) history of solid or hematological neoplasia or bone marrow transplantation (except for basal cell carcinoma and completely excised squamous cell carcinoma)
• •13. Other severe acute or chronic medical or psychiatric conditions or pre-dispositions or laboratory abnormalities, as judged by the Investigator
• •14. Current or past history of coagulation disorders (according to local laboratory ranges), as judged by the Investigator
• •15. Hypersensitivity to any components of hyaluronic acid (HA)-based injection products
• •16. Hypersensitivity to human biological material including blood and blood-derived products, potential excipients and residues from manufacturing process, documented clinically or by laboratory tests
• •17. Hypersensitivity to avian proteins Current or previous treatment
• •18. Participation in another clinical trial within 3 months prior to screening (within 1 year prior to screening if disease-modifying OA drug (DMOAD) received and if the Investigator considers it could impact the safety or efficacy assessment)
• •19. Subject previously treated with JTA-004 within 2 years prior to screening
• •20. Subject treated with intra-articular viscosupplement or blood-derived product (e.g., platelet-rich plasma) injection in the target knee within 6 months prior to screening
• •21. Subject treated with intra-articular glucocorticoid injection in the target knee within 4 months prior to screening
• •22. Subject having started the use of slow acting drugs for OA such as glucosamine, glucosamine sulfate, chondroitin sulfate, diacerein, curcumin, soybean/avocado extracts or related products within 1 month prior to screening
• •23. Current chemo-, radio- or immuno-cancer-therapy or immunosuppressive therapy
• •24. Chronic (≥ 3 days/week within the last 3 months) use of opioids other than weak opioids (such as codeine, dihydrocodeine, tramadol…)
• •25. Chronic (\> 15 consecutive days) use of systemic steroids Safety aspects concerning female subjects of childbearing potential
• •26. Breast-feeding
• •27. Pregnancy
• •28. Woman with positive pregnancy test
• •29. Woman not willing or not able to use a highly effective contraceptive method during the 6-month active follow-up period. Highly effective birth control methods are:
• •1. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
• •2. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
• •3. Intrauterine device
• •4. Intrauterine hormone-releasing system
• •30. Body Mass Index (BMI) of 40 kg/m2 or greater at baseline
• •31. Signs of an active drug or alcohol dependence, serious current illness, mental illness or any other factors which may interfere with subject's ability to understand and comply with study requirements, as judged by the Investigator
• •32. Life expectancy less than 12 months at screenin