clinical study of artz in the treatment of knee osteoarthritis

Conditions: Knee Osteoarthritis

Summary: this is a multi-center, randomized, open-label, parallel-arm phase iv clinical study, for which a total of 300 patients with mild to moderate knee osteoarthritis will be enrolled. in the first 4 weeks (run-in period), the subjects will receive on-demand treatment with diclofenac sodium sustained release tablets (dicl-sr) 75mg, quaque die（qd）. after the run-in period, the subjects, if their knee pain has not worsened to a level requiring surgical treatment, will be randomized to two groups in 1:1 ratio: one group receiving artz® via intra-articular injection (once weekly, for 5 consecutive weeks) in combination with dicl-sr 75mg,quaque die（qd）, for 12 consecutive weeks on demand. the other group receiving dicl-sr 75mg alone,quaque die（qd）, for 12 consecutive weeks on demand. dicl-sr 75mg quaque die（qd） may be administered to the subjects of both groups on demand as long as they have a knee pain. if the knee pain has disappeared, this drug may be withdrawn. however, if the pain occurs again and requires treatment, oral administration of dicl-sr may be resumed. a subject is allowed to withdraw from this study prematurely if unable to tolerate the adverse effects. a total of 8 visits have been scheduled for this study, including visit 1/screening period (week -4), visit 2/baseline (week 0), visit 3 (week 1), visit 4 (week 2), visit 5 (week 3), visit 6 (week 4), visit 7 (week 8) and visit 8 (week 12). a total of 300 subjects will participate in this study at 6 to 8 centers in china, and patient enrollment is expected to take up to 12 months.


Eligibility criteria:
inclusion criteria: 1. adult chinese subjects, at age≥18, either gender, diagnosed with osteoarthritis of the target knee and kellgren-lawrence (kl) classification grade 1\~3, as evidenced by x-ray examination in the last 3 months (mild to moderate narrowing of joint space and / or marked osteophytes of tibiofemoral joint space) 2. persist pain of the target knee after exercise, weight loss and physical therapy; 3. a baseline womac a1 score for the target knee rated at 40-90mm (moderate to severe walk-associated pain) on 100mm visual analogue scale(vas); able to understand and sign the informed consent form (icf) that has already been approved by the independent ethics committee (iec) note: the informed consent may also be given by the duly authorized representative of the subject. exclusion criteria: 1. a diagnosis of bilateral knee osteoarthritis; 2. clinically significant (requiring surgery) valgus or varus deformity of the knee joint, ligamentous laxity or unstable meniscus; 3. complicated by inflammation or any other disease /condition (e.g., rheumatic arthritis, metabolic bone disease, psoriasis, gout, pseudogout, chondrocalcinosis, etc.) that may affect the knee joint; 4. a history of septicemia, clinically considered sub-acute infection of the target knee joint; 5. a history of surgery on the target knee (in the last 6 months); 6. a history of asthma, urticaria or allergy after use of aspirin or other non-steroidal anti-inflammatory drugs (nsaids); 7. severe hepatic or renal disease or hepatic /renal failure; 8. any unscheduled surgery on the lower limb; 9. clinically significant lower venous or lymphatic obstruction; 10. clinically significant obvious exudation or inflammation of the target knee; 11. skin disorders or infection at the injection site; 12. pregnant or lactating women; 13. known allergy to guanylin and / or any active ingredient or excipient of hyaluronic acid-based injection / diclofenac sodium; 14. treatment with any hyaluronic acid (ha) or its derivatives for the target knee within six months before this trial; 15. intra-articular (ia) injection of steroids into the target knee within 3 months before this trial; 16. presence of any contraindication to ia injection, e.g., patients who are receiving anti-coagulation therapy or clinically have potential coagulation disorders (e.g., hepatic disease); 17. presence of any clinically significant disease (e.g., significant mental or nervous disorders, alcohol/drug abuse), unstable/poorly controlled diseases, or other factors, which may affect their evaluation or participation in this study in the investigator's judgment 18. perioperative pain associated with coronary artery bypass surgery (cabg); 19. a history of gastrointestinal bleeding or perforation following use of nsaids; 20. presence of active gastrointestinal ulcer /bleeding, or a past history of recurrent ulcer/bleeding; chief complaint complicated by pain beyond the target knee,

Keywords: sodium hyaluronate mild to moderate knee osteoarthritis