Primary Objective: To explore the effectiveness of different doses of HRS-2129 in the treatment of patients with moderate to severe pain in knee osteoarthritis. Secondary Objectives: To evaluate the safety of different doses of HRS-2129 for the treatment of patients with moderate to severe pain in knee osteoarthritis; To evaluate the population pharmacokinetic profile of HRS-2129 in patients with knee osteoarthritis.

Inclusion Criteria:

1. Voluntarily sign the informed consent form before starting the activities related to the trial;
2. The Numerical Evaluation Scale (NRS) pain score of the index knee joint at screening is ≥ 4;
3. Subjects must be willing to discontinue all medical and non-medical treatments for osteoarthritis pain except rescue medication (acetaminophen) and not use prohibited analgesics throughout the study ;
4. Male and female subjects of childbearing potential must agree to use highly effective contraceptive measures with their partners from the signing of the informed consent form until 1 month after the last dose of investigational product.

Exclusion Criteria:

1. History of other diseases that may involve the target joint;
2. History of major trauma or surgery of knee joint and hip joint in the past year;
3. Plan to undergo surgical procedure during the study;
4. Most or complete loss of mobility;
5. There are other diseases that may confuse the assessment of osteoarthritis pain;
6. There is a neuropsychiatric disease, and the investigator's assessment may affect the evaluation of osteoarthritis (OA) or self-score;
7. There are serious or poorly controlled concomitant diseases;
8. Those who have a clear history of peptic ulcer, bleeding, perforation or obstruction within 1 year before screening, and have been clinically diagnosed;
9. Those who require drug treatment or surgical intervention;
10. History of malignant tumors within 5 years before screening;
11. Have a history of drug abuse, drug abuse and/or alcoholism within 2 years before screening.