ASKC200 for Knee Osteoarthritis Pain

Inclusion criteria

Subjects must meet all of the following criteria:

• Provide signed informed consent before undergoing any examinations or assessments, and understand and comply with the study requirements;
• Aged 40 to 80 years (inclusive) at the time of signing the informed consent, male or female;
• Diagnosed with primary knee osteoarthritis based on clinical and radiological examinations;
• History of knee osteoarthritis pain lasting ≥ 6 months;
• Within 3 months prior to dosing, X-ray of the tibiofemoral joint shows Kellgren-Lawrence Grade II or III in the target knee, with the contralateral knee grade not higher than the target side;
• Before the first dose, the weekly average of the daily mean pain NRS score in the target knee is ≥ 4 and < 8, and the weekly average of the daily mean pain NRS score in the contralateral knee is < 4;
• Before the first dose, the WOMAC pain scale score for the target knee is ≥ 20, and the WOMAC pain scale score for the contralateral knee is < 20;
• Willing to discontinue the use of non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and other analgesics, and to use only study-provided acetaminophen as rescue medication for knee osteoarthritis pain during the study period;
• Body Mass Index (BMI) ≤ 40.0 kg/m²;
• Male and female subjects of childbearing potential agree to voluntarily adopt effective contraceptive measures and have no plans for pregnancy, egg donation, or sperm donation from the screening period through 3 months after the last dose. Female subjects of childbearing potential must have a negative pregnancy test before the first use of the study drug.

Exclusion criteria

Subjects will be excluded from the study if they meet any of the following criteria:

• Secondary arthritis due to other causes (e.g., psoriasis, ankylosing spondylitis, rheumatoid arthritis, systemic lupus erythematosus, etc.);
• The target knee has other conditions that may affect the function and pain assessment of the target knee (e.g., fractures, osteonecrosis, and chondrocalcinosis within 6 months prior to screening, etc.);
• Presence of other diseases causing pain in the target knee (e.g., hip pain, lumbar spinal stenosis, intermittent claudication, etc.) or pain in other areas that, in the investigator's judgment, may affect the assessment of knee osteoarthritis pain;
• Use of other medications for osteoarthritis within 1 week prior to the first dose, such as NSAIDs (except aspirin ≤ 325 mg/day for cardiac prophylaxis), analgesics (except rescue acetaminophen used continuously for ≤ 3 days), symptomatic slow-acting drugs for osteoarthritis (diacerein, glucosamine, chondroitin sulfate, etc.), anxiolytics (doxepin, amitriptyline, pregabalin, etc.), or traditional Chinese medicines (containing active ingredients such as artificial tiger bone powder, Psammosilene tunicoides, etc.), whether oral or topical;
• The target knee has pathological joint effusion requiring aspiration or has surgical indications;
• Presence of chronic pain in other body parts requiring long-term oral analgesic therapy, or need for concomitant systemic glucocorticoid therapy from 4 weeks prior to the first dose through the study period;
• Open knee injury or other knee surgeries (e.g., arthroscopy, arthroscopic debridement, knee replacement, etc.) on the target knee within 6 months prior to the first dose;
• Undergone any major surgical procedure within 3 months prior to the first dose;
• Received intra-articular injection therapy (e.g., corticosteroids or sodium hyaluronate, etc.) in the target knee within 3 months prior to the first dose;
• Received treatment with other investigational drugs or devices within 4 weeks prior to the first dose;
• Received physical therapy (e.g., electrotherapy, etc.) for knee osteoarthritis in the target knee within 3 months prior to the first dose;
• Patients who are unable to ambulate independently and require assistive devices for more than 50% of ambulation time within 4 weeks prior to the first dose;
• Applied any capsaicin-containing products or NSAIDs to the skin of the target knee within 2 weeks prior to the first dose;
• History of allergy, contraindication, or intolerance to any component of the investigational product ASKC200 liniment, the comparator diclofenac diethylamine emulgel, or the rescue medication acetaminophen, or to any other NSAIDs;
• Presence of open wounds, skin erythema or edema, skin infection, or any other skin lesions on the target knee prior to the first dose that, in the investigator's opinion, may affect subject safety or absorption of the study drug;
• Instability of the target knee, such as cruciate ligament tear, ligamentous laxity, or significant valgus/varus deformity;
• History of gastrointestinal bleeding within 6 months prior to screening;
• Subjects planning to undergo surgery during the study period (including but not limited to general surgery, orthopedic surgery, gynecological/obstetric surgery, etc.);
• In the investigator's judgment, subjects have any clinically significant unstable cardiovascular, cerebrovascular, respiratory, neurological, immunological, hematological, hepatic, renal, or endocrine systemic disease that remains uncontrolled despite standard treatment;
• Abnormal liver function tests (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, total bilirubin ≥ 1.5 × ULN);
• Abnormal renal function tests (creatinine ≥ 1.5 × ULN);
• Clinically significant abnormalities on 12-lead ECG that, in the investigator's judgment, preclude participation, including but not limited to prolonged QTcF interval (defined as > 450 ms in males or > 470 ms in females), second-degree or third-degree atrioventricular block;
• Subjects with uncontrolled hypertension without medication, or hypertension that remains uncontrolled despite medication (defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg);
• History of malignancy within 5 years (excluding successfully treated non-metastatic cutaneous squamous cell carcinoma or basal cell carcinoma and/or cervical carcinoma in situ);
• History of alcohol or drug dependence within 12 months prior to the first dose;
• Psychiatric disorders that may affect the subject's ability to comply with study procedures or complete the study (including but not limited to a history of mania, bipolar disorder, schizophrenia, or schizoaffective disorder);
• Pregnant or breastfeeding women;
• Subjects deemed by the investigator to have poor compliance or other reasons that make them unsuitable for participation in this study.