A Study Evaluating the Safety, Tolerability, and Efficacy of SM04690 Injected in the Target Knee Joint of Moderately to Severely Symptomatic Osteoarthritis Subjects

Inclusion Criteria

• Males and females between 40 and 80 years of age, inclusive, in general good health
• Ambulatory (single assistive devices such as canes allowed if needed less than 50% of the time, subjects requiring a walker are excluded)
• Established diagnosis of primary femorotibial OA in the target knee by standard American College of Rheumatology (ACR) criteria for at least 6 months (clinical AND radiographic criteria); if bilateral knee OA is present, the target knee is defined as the knee with greater pain at screening based on the subject's evaluation and the Investigator's clinical judgment
• Radiographic disease Stage 2 or 3 in the target knee according to the Kellgren-Lawrence grading of knee OA as assessed by independent central readers
• Screening pain visual analog scale (VAS) score of 30-80 mm (on a scale of 0-100 mm) for the target knee while on symptomatic oral treatment at screening (if the subject requires oral treatment)
• Total WOMAC score of 72-192 (out of 240) for the target knee while on symptomatic oral treatment at screening (if the subject requires oral treatment)
• Willingness to omit the following for 24 hours prior to all Study Visits, excluding the Screening Visit:
• Pain medications
• Medications or supplements for the treatment of OA
• Participation in a formalized in-office and/or supervised OA disease program (e.g., a prescribed patient education program, physiotherapy, etc.)
• Full understanding of the requirements of the study and willingness to comply with all study visits and assessments
• Subjects must have read and understood the informed consent form, and must have signed it prior to any study-related procedure being performed
• Subject's Day 1 visit must occur while enrollment into the study is open

Exclusion Criteria

• Women who are pregnant or lactating
• Women of childbearing potential (i.e., who are not surgically sterile or postmenopausal as defined by no menstrual periods for 12 consecutive months and no other biological or physiological cause for amenorrhea can be identified); males who are sexually active and have a partner who is capable of becoming pregnant, neither of which have had surgery to become sterilized, who are not using an effective method of birth control (e.g., surgically-implanted hormonal therapy, intrauterine devices or oral birth control with barrier method)
• Body mass index (BMI) >40
• Partial or complete joint replacement in the target knee
• Previous exposure to SM04690
• Major surgery (e.g., interventional arthroscopy) in the target knee within 52 weeks prior to any study injection
• Any planned or elective surgery during the study period
• Significant and clinically evident misalignment of the target knee that would impact subject function, as determined by the Investigator
• History of malignancy within the last 5 years; however, subjects with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Subjects with other malignancies are eligible if they have been continuously disease free for at least 5 years prior to any study injection
• Clinically significant abnormal Screening Visit hematology values, blood chemistry values, HbA1c, or urinalysis values as determined by the investigator
• Any condition, including laboratory findings (not included in the Screening Visit laboratory tests) and findings in the medical history or in the pre-study assessments, that, in the opinion of the Investigator, constitutes a risk or contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation
• Comorbid conditions that could affect pain assessment of the target knee, including, but not limited to, inflammatory rheumatic conditions such as rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, diabetic neuropathy, pseudogout, gout, and fibromyalgia
• Other conditions that, in the opinion of the Investigator, could affec