Clinical Study of Artz in the Treatment of Knee Osteoarthritis
Clinical Study of Artz in the Treatment of Knee Osteoarthritis
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 If the knee pain has disappeared, this drug may be withdrawn.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.
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,