Study to Evaluate Resiniferatoxin in Patients With Knee Osteoarthritis Whose Total Knee Replacement Surgery is Delayed

Inclusion Criteria: * Able to give informed consent and comply with the study * Diagnosis of osteoarthritis (OA) in the index knee * Combined WOMAC A (pain) and C (function) subscale score of ≥ 23 at screening, using the WOMAC 5-point Likert scale * Eligible for total knee replacement (TKR) surgery but unable to schedule surgery or undergo scheduled surgery * In good general health; American Society of Anesthesiologists (ASA) physical status category ≤3 * Willing to use contraception for at least 30 days after receiving the study drug * Able to understand and complete study-related forms and adequately communicate with the Investigator and site staff Exclusion Criteria: * Pre-existing osteonecrosis, subchondral insufficiency fracture, or knee pain attributable to disease other than OA which may confound the ability to assess response to treatment * Concurrent medical or arthritic conditions that could interfere with evaluation of the index knee joint including, metabolic diseases, gout/pseudogout, hemochromatosis, acromegaly, fibromyalgia, rheumatoid arthritis, or other inflammatory arthropathies affecting the knee joint * Participants with significant pain in the back or other joints (ex. hip pain) which may confound discrimination of pain assessment in index knee, as judged by the Investigator * Undergone arthroscopic surgery of the index knee within 6 months of study drug administration, or open surgery to the index knee within 24 months of study drug administration * Undergone replacement surgery of the index knee * Presence of surgical hardware or other foreign bodies in the index knee * Index knee injections with corticosteroids within 30 days, or hyaluronic acid within 3 months, or platelet-rich plasma within 6 months prior to study drug administration. * Concurrent use of opioids for indications other than knee pain * Arterial or venous thrombi (including stroke), myocardial infarction, hospital admission for unstable angina, cardiac angioplasty, or stenting within 12 months prior to Screening. * Sensory peripheral neuropathy in the distal aspect of the target limb that is of moderate severity or higher at Screening * Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome-related illness, acute or history of chronic hepatitis B or hepatitis C; positive tests for HIV-1 or -2 antibodies, hepatitis B surface antigen, or hepatitis C antibodies * Specified laboratory abnormalities within 1 week of study drug administration * History within the past 2 years of substance abuse, including alcohol * Allergy or hypersensitivity to chili peppers, capsaicin, resiniferatoxin, acetaminophen, tramadol, radiographic contrast agents, or any of the agents to be used for sedation, anesthesia or nerve block on the day of study drug administration * Female participants who are pregnant, planning on becoming pregnant within 30 days of receiving study drug, or are breastfeeding at Screening * Any medical condition or medical comorbidities that, in the Investigator's opinion, could adversely impact study participation or safety, conduct of the study, or interfere with pain assessments * Participated in a clinical study of an investigational drug within 4 half-lives of Screening or are scheduled to receive an investigational agent (therapy or device) while participating in this study