A Phase Ib Study to Evaluate the Efficacy and Safety of HRS-2129 in Patients With Knee Osteoarthritis

• HRS-2129 Tablet (Drug): HRS-2129 tablet.
• Celecoxib capsule (Drug): Celecoxib capsule.
• Celecoxib Capsule Placebo (Drug): Celecoxib capsule placebo.
• HRS-2129 Tablet Placebo (Drug): HRS-2129 tablet placebo.

Primary outcomes

• Change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale scores. [At week 4.]

Secondary outcomes

• Change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale scores. [From baseline to Week 1, 2 and 3.]
• Change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) joint function subscale scores. [From baseline to Week 1, 2, 3 and 4.]
• Change from baseline in the weekly mean (Week 1, 2, 3 and 4) of the index Knee Numerical Rating Scale (NRS) pain score (resting). [From baseline to Week 1, 2, 3 and 4.]
• Change from baseline in the weekly mean (Week 1, 2, 3 and 4) of the index Knee Numerical Rating Scale (NRS) pain score (flat walking). [From baseline to Week 1, 2, 3 and 4.]
• Change from baseline in the overall patient global assessment (PGA) of osteoarthritis condition using the 5-point Likert scale. [From baseline to Week 1, 2, 3 and 4.]
• Change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) stiffness subscale scores. [From baseline to Week 1, 2, 3 and 4.]
• Change from baseline in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. [From baseline to Week 1, 2, 3 and 4.]
• Treatment response: WOMAC pain subscale scores decreased by ≥ 30%, ≥ 50%, ≥ 70% from baseline. [At Week 1, 2, 3 and 4.]
• Adverse events (AEs) occurred during the study. [During the study, approximately 8 months.]: To evaluate the safety and tolerability of HRS-2129 tablets.
• Serious adverse events (SAEs) occurred during the study. [During the study, approximately 8 months.]: To evaluate the safety and tolerability of HRS-2129 tablets.

Sex: All, ages: 18 Years to 80 Years

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.