Evaluating the Efficacy and Safety of Intra-articular Injection of HS-20116 in Patients With Knee Osteoarthritis

This is a prospective, randomized, single-blind, active-controlled, multicenter clinical study to evaluate the efficacy and safety of intra-articular injection of HS-20116 in patients with knee osteoarthritis. Eligible subjects after screening will be randomized in a 1:1 ratio into the test group and the control group. Test group subjects will receive a single intra-articular injection of HS-20116 (3 mL) into the treated knee on Day 0. Control group subjects will receive 2-3 intra-articular injections of chitosan (2-3 mL each) on Day 0 and Day 14, with an optional injection on Day 28. The primary endpoint is the change from baseline in WOMAC pain score at Week 12 after the first injection. Each subject may choose to participate in an optional long-term follow-up visit between Weeks 22 and 28.

Inclusion criteria

• Males or females aged 40-85 years (inclusive);
• Body mass index (BMI) ≤ 35 kg/m2;
• Primary knee osteoarthritis in accordance with the clinical and radiological diagnostic criteria of the American College of Rheumatology (ACR), unilateral or bilateral femorotibial arthritis, with or without patellofemoral arthritis;
• A radiographic Kellgren and Lawrence (K&L) grade of II to III in the treated knee within 6 months prior to randomization;
• Recurrent knee pain for at least 6 months at screening, with no or poor response to the first-line oral non-opioid analgesics and non-steroidal anti-inflammatory drugs (NSAIDS);
• After a washout period of 48 h for analgesics, the degree of pain before bilateral knee injection was assessed using the WOMAC pain score (5-grade Likert method) prior to randomization, which should meet the following criteria:

• Treated knee: WOMAC pain score of 7-17, of which item A1 was at least 2;
• Non-treated knee: WOMAC pain score of no more than 6.
• Completely free to move;
• Willing to undergo a 48-h analgesic washout period prior to visit;

Exclusion criteria

• Concomitant synovial chondromatosis and villonodular synovitis of the knee;
• Patellofemoral osteoarthritis only, where symptoms including pain mostly originated from the patellofemoral joint (patellofemoral pain syndrome);
• Onset of clinically significant knee effusion, knee inflammation or associated symptoms, or abnormal gross examination or volume of synovial fluid at the time of joint aspiration on the day of injection;
• Obvious varus or valgus deformity of the treated knee after clinical evaluation or imaging evaluation as judged by the investigator;
• Concomitant autoimmune diseases, autoinflammatory diseases, or infectious arthritis, such as rheumatoid arthritis, psoriatic arthritis, articular chondrocalcinosis, gout, ankylosing spondylitis, and lupus erythematosus;
• Other concomitant pathological changes affecting joint treatment/evaluation, such as arthrodysplasia, ipsilateral hip osteoarthritis, aseptic bone necrosis, acromegaly, Paget's disease, hemophilia, hemochromatosis, lumbosacral radicular pain, femoral nerve or sciatic nerve radicular pain, venous or lymphatic obstruction, arteritis, tendon disorder, etc.;
• Skin infection, skin lesions, or chronic dermatosis at the puncture site;
• Any knee injury, surgical history, or arthroscopy and treatment within 6 months prior to screening; or any surgery or other invasive operation expected to be performed during the trial;
• Prior injection with hyaluronic acid into the treated knee within 6 months prior to randomization.