Phase Ib Trial of Injectable RAB001 for Knee Osteoarthritis

Inclusion criteria

• (1) Aged from 40 to 75 years inclusive; (2) Diagnosis of knee osteoarthritis consistent with the diagnostic criteria in the Guidelines for the Diagnosis and Treatment of Osteoarthritis issued by the Joint Surgery Group, Orthopaedic Branch of Chinese Medical Association (2024); (3) Received conservative management (e.g., physical therapy, analgesics) for ≥4 weeks with persistent pain in the target knee; the VAS score of WOMAC Item A1 (walking pain) is ≥40 mm and ≤80 mm at screening and baseline; (4) Target knee is graded as Kellgren-Lawrence Grade I-III; the contralateral knee shall not have a higher KL grade than the target knee. In case of identical grades for both knees, the right knee is defined as the target knee; (5) Body mass index (BMI) ranges from 18 to 30 kg/m² inclusive; (6) Provides written informed consent voluntarily prior to any study-related procedures.

Exclusion criteria

• (1) Unable to ambulate (subjects using walking aids for ≥12 weeks prior to screening visit may continue such aids throughout the study); (2) VAS pain score ≥40 mm in any joint other than the target knee at screening and baseline visits.

(3) Subjects with osteoarthritis of the ipsilateral hip; (4) Subjects with substantial target-knee joint effusion judged by the investigator to be ineligible for enrollment; (5) Subjects with active septic arthritis of the target knee, skin breakdown/infection at the injection site, or any significant chronic dermatosis that may interfere with intra-articular injection and/or injection-site safety assessment; (6) Subjects unable to discontinue permitted analgesics within 48 hours prior to efficacy assessments; (7) Subjects receiving systemic corticosteroids within 12 weeks before screening; (8) Subjects with septic arthritis in any joint within 12 weeks before screening; (9) Subjects exposed to any investigational medicinal product, device or biologic within 12 weeks before screening; (10) Subjects receiving intra-articular corticosteroid injection into the target knee within 24 weeks before screening; (11) Subjects receiving viscosupplementation injection (sodium hyaluronate, medical chitosan) in the target knee within 24 weeks before screening; (12) Subjects who underwent major lower-extremity surgery, arthroplasty or arthroscopy on target knee or other lower-limb joints within 24 weeks before screening, or with planned lower-limb surgery during study period; (13) Subjects with secondary knee osteoarthritis induced by acute disease or trauma within 5 years before screening; (14) Subjects with active malignancy or history of anti-tumor therapy within 5 years before screening, excluding non-melanoma skin cancer; (15) Subjects with inflammatory arthropathies or relevant disorders involving joints (e.g., rheumatoid arthritis, metabolic bone disease, psoriatic arthritis, gout, symptomatic chondrocalcinosis, osteonecrosis or active infection); (16) Subjects with marked varus/valgus deformity, ligamentous laxity or unstable meniscus; (17) Subjects with chronic painful conditions (VAS ≥40 mm) at screening or peripheral/central neuropathy impairing sensory function around target knee, including but not limited to back pain, hip pain, intervertebral disc herniation, sciatica, diabetic neuropathy, post-stroke pain or fibromyalgia; (18) Subjects with pulmonary diseases such as asthma or COPD requiring regular systemic/inhaled corticosteroid treatment during study; (19) Subjects with venous or lymphatic stasis of lower extremities; (20) Subjects with claudication or peripheral arterial disease; (21) Subjects on ongoing oral/parenteral anticoagulation or high-dose antiplatelet therapy (daily aspirin ≤100 mg and/or antiplatelet agents such as clopidogrel, ticagrelor are permitted); (22) Subjects on chronic regular intake of paracetamol or nonsteroidal anti-inflammatory drugs (NSAIDs); (23) Subjects with severe systemic illnesses including myocardial infarction, heart failure, unstable angina, cerebrovascular disease, severe renal insufficiency, etc.; (24) Subjects with severe hepatic impairment or relevant medical history; (25) Subjects with abnormal coagulation parameters; (26) Subjects with known hypersensitivity to any component of investigational product or paracetamol, or severe allergic constitution as assessed by investigator; (27) Female subjects with positive pregnancy test, breastfeeding, unwilling to implement effective contraception or planning pregnancy during trial; (28) Subjects with any other conditions deemed inappropriate for study enrollment by the investigator.