A Phase 3 Efficacy and Safety Study of Intra-articular CNTX-4975-05 (Capsaicin) vs Placebo in Subjects With OA Knee Pain

Key Inclusion Criteria: * Male or female subjects between 40 and 95 years of age (inclusive) at the time of the Screening Visit with the ability to comply with answering the electronic diary using the study-provided tablet computers. * Confirmation of osteoarthritis (OA) of the knee. * Confirmation of OA of the index knee. * Moderate to severe pain in the index knee associated with OA must be stable for a minimum of 6 months prior to Screening, as assessed by the investigator. * BMI ≤45 kg/m\^2. * Must have failed 2 or more prior therapies. * Females not of childbearing potential, defined as post-menopausal for at least 1 year, or surgically sterile, or practicing one of the following medically acceptable methods of birth control throughout the study period. * Subject agrees to stay on their current pain medication (including over the counter (OTC) medications) from the time of Screening through Week 12. The current pain medication must be taken only for pain in the index knee, and not for another pain indication. * Subject agrees to take only the allowed rescue medications for OA knee pain of the index knee from the time of Screening through study completion and agrees to use no topical medications for OA knee pain during the trial. Key Exclusion Criteria: * Joint replacement surgery of the index knee at any time, or open surgery of the index knee in the past 24 months. * Prior arthroscopic surgery of the index knee within 6 months of Screening. * Any painful conditions of the index knee due to joint disease other than OA. * Periarticular pain from any cause. * Pain in the non-index knee that is \>3 on a numeric pain rating scale (NPRS) (0-10) when walking or at rest. * Other chronic pain anywhere in the body that requires the use of analgesic medications. * Instability of the index knee. * Misalignment (\>10 degrees varus or valgus) of the index knee on standing. * Documented history of neuropathic arthropathy or finding of bony fragmentation in the index knee with imaging. * Physical/ occupational/ chiropractic therapy for the lower extremities or acupuncture for the lower extremities within 30 days of Screening, or need for such therapy during the study. * Plans to have surgery, other invasive procedures, or IA injections while participating in the study. * Has used topical capsaicin on the index knee within 90 days of Screening. * Current use of opioids for any condition other than for OA of the index knee. * Corticosteroid injection into the index knee within 90 days of Screening. * Received IA viscosupplementation (eg, Synvisc®, Hyalgan®) within 90 days of Screening.