A Phase 3 Study to Evaluate the Efficacy and Safety of Resiniferatoxin for Pain Due to Osteoarthritis of the Knee

This study evaluates the efficacy and safety of intra-articular injection of resiniferatoxin in patients with moderate to severe knee pain due to osteoarthritis.

This study is to evaluate the analgesic efficacy and safety of resiniferatoxin administered intra-articularly to subjects with moderate to severe knee pain due to osteoarthritis (OA).

Eligibility Criteria:
Key Inclusion Criteria:

* Male or female 35 to 85 years of age (inclusive).
* Diagnosis of moderate to severe pain in the index knee due to OA.
* Pain in the non-index knee is less than pain in the index knee.
* Body mass index ≤40 kg/m².
* Experienced treatment failure with at least 2 prior categories of therapies.
* Able to understand and complete study-related forms and communicate with the Investigator and/or site staff.

Key Exclusion Criteria:

* Evidence or history of a serious coagulopathy or hemostasis problem, such as inherited bleeding disorders or thrombocytopenia.
* History of or current condition of poorly controlled hypertension, QTc prolongation, history of risk factors for Torsades de Pointes, or family history of long QT syndrome; or is using concomitant medications that prolong the QT interval.
* Received index knee injections with corticosteroids within 30 days, or hyaluronic acid within 3 months, or platelet-rich plasma within 6 months prior to the injection day.
* Pre-existing osteonecrosis, subchondral insufficiency fracture, severe bone on bone OA, or knee pain attributable to disease other than OA.
* Instability or misalignment in the index knee.
* Concurrent use of opioids or indications other than knee pain.
* History within the past 2 years of substance abuse, including alcohol.
* Allergy or hypersensitivity to chili peppers, capsaicin, resiniferatoxin, acetaminophen, tramadol, or radiographic contrast agents.
* Female participants who are pregnant, planning on becoming pregnant, or currently breastfeeding.
* Any medical condition or comorbidities that, in the Investigator's opinion, could adversely impact study participation or safety, conduct of the study, or interfere with pain assessments.
* Sensory peripheral neuropathy that is of moderate severity or higher.
* Arterial or venous thrombi (including stroke), myocardial infarction, hospital admission for unstable angina, cardiac angioplasty, or stenting within the past 12 months.
* Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome-related illness, acute or history of chronic hepatitis B or hepatitis C. Participants with these viral infections who are receiving or have received antiviral treatment and have a viral load that is undetectable are eligible.
* Concurrent medical or arthritic conditions that could interfere with the evaluation of the index knee joint including chondromalacia patellae, metabolic diseases, gout/pseudogout, hemochromatosis, acromegaly, fibromyalgia, rheumatoid arthritis, or other inflammatory arthropathies affecting the knee joint.
* Undergone arthroscopic surgery of the index knee within 6 months of the injection day, or open surgery to the index knee within 24 months of the injection day.
* Undergone replacement surgery of the index knee.
* Presence of surgical hardware or other foreign bodies in the index knee.