Study to Evaluate the Efficacy and Safety of EP-104IAR in Patients With Osteoarthritis of the Knee

Key Inclusion Criteria: * Males or females, aged ≥40 years * Body Mass Index (BMI) ≤ 40.0 kg/m2 * Diagnosis of primary OA of the Index knee, with symptoms present for at least 6 months * OA severity Grade 2 or 3 (based on Kellgren Lawrence Grading Scale) * Unsatisfactory pain relief from at least 2 prior standard OA treatments * Qualifying pain in the Index knee during the baseline period * Ambulatory (without the need for a cane/other walking aide) * Female subjects willing to use highly effective birth control methods to prevent pregnancy * Willing and able to comply with study procedures and restrictions, including abstaining from use of restricted medications. Key Exclusion Criteria: * OA of the Index knee due to acute injury or trauma, or unstable joint * X-ray evidence of chondrocalcinosis * Diagnosed or suspected ipsilateral hip OA * Knee pain that is not attributable to OA of the knee * Any other disorders that impact mobility, strength or sensation, or are a co-existent source of pain or inflammation that interfere with assessment of knee pain and function * History of infection in the Index knee * Skin breakdown on the Index knee where the injection will take place * Total Knee Replacement, or any other surgery (including arthroscopy) for the Index knee within prior 12 months, or planned surgery during the study * Total Knee Replacement Surgery of the non-Index knee within prior 6 months, or planned surgery (any location) during the study that would require a restricted medication * IA injection of corticosteroids in any joint within prior 3 months or IA injection of extended-release corticosteroids in any joint within prior 6 months * IA injection in the Index knee of platelet rich plasma, or other prolotherapy within prior 3 months, or hyaluronic acid within prior 6 months * Recent, current or planned use of corticosteroids for any indication (except for permitted uses) * Recent, current or planned use of prohibited medications (including analgesics, marijuana, investigational drugs and devices, immunosuppressive therapy), or unwilling or unable to stop using prohibited medications during the study. * Conditions including: sarcoidosis, amyloidosis, osteomyelitis, Cushing's Syndrome, hepatic or renal disease, Psychotic disorder, bipolar disorder, symptomatic depressive or anxiety disorders. * Current malignancy of any type, or history of a malignancy within prior 12 months * Active or quiescent systemic fungal, bacterial (including tuberculosis) viral (including HIV, Hepatitis B or C) or parasitic infections, or ocular herpes simplex, or any recent infection requiring IV or oral antibiotics * Laboratory results indicative of adrenal insufficiency, diabetes or renal or hepatic disease. * Positive urine drug screen for a substance of abuse * Females who are pregnant, lactating * Known or suspected hypersensitivity or contraindication to ingredients in the study drug