A Study of Econoglutide Injection in Obese Participants With Knee Osteoarthritis (KOA)

In this Phase III study, eligible participants will be randomized into one of the two cohorts in a 1:1 ratio to receive once-weekly subcutaneous ecnoglutide injection or placebo, including a dose-escalation period, with the total treatment duration of up to 68 weeks, plus 5 weeks of follow-up period. The overall study will last for 73 weeks.

Inclusion criteria

• Body mass index (BMI) ≥ 28.0 kg/m^2;
• The target knee must meet the diagnostic criteria of American College of Rheumatology (ACR) for knee osteoarthritis (clinical and radiological), with moderate radiographic changes (Kellgren-Lawrence grade 2 or 3). The target knee is defined as the knee with the most symptomatic knee at screening period; if pain in both knees are equal, the target knee will be the most dominant leg (preferred leg);
• Prior to screening, target knee pain lasting more than 12 weeks, and according to participant's self-report or medical history at screening, target knee pain lasting more than 15 days in the past month;
• At screening and prior to randomization, WOMAC pain score (NRS 0-10) of the target knee must be between 4 and 9 (to avoid bias in reporting, participants must not be informed of the pain score used to determine eligibility for the study);
• Self-reported by the participant who has a history of unsuccessful weight loss attempt by diet and exercise.

Exclusion criteria

• The target knee has undergone joint replacement surgery;
• The target knee has undergone arthroscopy within 12 months prior to screening;
• At the time of screening, the target knee joint has any clinical features and symptoms of other active infections or crystal-induced arthropathies, as well as any other active joint diseases that may interfere with assessment;
• The target knee has received intra-articular injections of hyaluronic acid, any other investigational drugs, or biologics within 3 months prior to screening; or has undergone any procedures that result in persistent sensory loss in the target knee (e.g., ablation) within 6 months prior to screening;
• Has received any intramuscular or oral corticosteroids (investigational or marketed) within 30 days prior to screening, or has received any intra-articular corticosteroid injections (investigational or marketed) in any joint within 90 days prior to screening;
• History of joint instability in either knee within 12 months prior to screening, such as anterior cruciate ligament rupture or recent trauma;
• History of any other potentially causative and/or confounding diseases, including Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease-associated arthritis, sarcoidosis, amyloidosis, or fibromyalgia;
• Presence of symptomatic hip osteoarthritis at the time of screening, with the exception of those who have undergone hip replacement surgery;
• Conditions that may interfere with the assessment of target knee pain during screening include, but are not limited to:

• Pain in any part of the lower limb or back equal to or more severe than the pain in the target knee;
• Pain radiating to the knee from other areas, such as hip pain affecting the knee or radicular pain;
• Chronic widespread pain (including neuropathic pain);
• Change of body weight >5% within 3 months prior to screening (selfreported);
• Diagnosis of diabetes (excluding gestational diabetes), or with a history of diabetic ketoacidosis or hyperosmolar state/coma