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

A Phase 3 Placebo-controlled Study to Evaluate the Efficacy and Safety of Intra-articular Administration of Resiniferatoxin Versus Placebo for the Treatment of Moderate to Severe 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).

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.