Comparison of a Single RTX-GRT7039 and Placebo Intra-articular Injection for Pain Associated With Osteoarthritis of the Knee

Inclusion Criteria: * The participant has given written informed consent to participate. * The participant is 18 years of age or older at the Screening Visit. * The participant has a diagnosis of osteoarthritis of the knee based on American College of Rheumatology criteria and functional capacity class of I to III. * There is a documented history indicating that participant has insufficient pain relief with previous Standard of Care. Exclusion Criteria: * The participant has past joint replacement surgery of the index knee. * The participant has a history of significant trauma or surgery (e.g., open or arthroscopic) to the index knee within 12 months of Screening. * The participant has periarticular pain from any cause other than osteoarthritis, including referred pain, bursitis, or tendonitis. * The participant has clinical hip osteoarthritis on the side of the index knee. * The participant has pre-existing osteonecrosis, subchondral insufficiency fracture, atrophic osteoarthritis, severe bone on bone osteoarthritis, knee pain attributable to disease other than osteoarthritis, or the participant has rapidly progressing osteoarthritis (RPOA) Type I or Type II. * The participant has significant malalignment of anatomical axis (medial angle formed by the femur and tibia) of the target knee (varus \>10, valgus \>10) by X-ray as assessed by independent Central Readers at Screening Visit. * The participant has other conditions that could affect trial endpoint assessments of the index knee. * The participant has current clinically significant disease(s) or condition(s) that may affect efficacy or safety assessments, or any other reason which, in the investigator's opinion, may preclude the participant's participation in the full duration of the trial. * The participant has a history of hypersensitivity to resiniferatoxin (RTX) or any similar component (capsaicin, chili peppers). * The participant is currently participating or was participating in another investigational drug trial within 3 months prior to the Screening Visit. * The participant is an employee of the investigator or trial site, with direct involvement in the proposed trial or other trials under the direction of that investigator or trial site or is a family member of the employees or the investigator.