Clinical trial: Study of Resiniferatoxin for Knee Pain in Moderate to Severe Osteoarthritis (NCT03542838)

Eligibility criteria:
Inclusion criteria:

          1. Age: 35 years to 85 years

          2. Diagnosis of moderate to severe pain due to OA: Moderate to severe osteoarthritis,
             based on American College of Rheumatology (ACR) criteria

          3. BMI < 45 kg/m2

          4. Pain in the target knee has been treated with at least 2 analgesic agents, including
             at least one NSAID

          5. Prior failure in at least two prior analgesic agents (at least one NSAID)

          6. Willing to abstain from other intra-articular treatments of the knee or any knee
             surgery for at least 24 weeks after treatment

          7. Ability to comply with the study and give informed consent

          8. If on an opioid medication, stable dose for at least 4 weeks prior to injection with
             no increase in dose leading up to study injection

          9. If on NSAIDs, be on a stable analgesic regimen for at least 4 weeks prior to injection

         10. If on pain regimens other than opioid medication or NSAIDs, be on a stable regimen for
             at least 30 days

         11. Is in good general health and is considered to have a physical status that is American
             Society of Anesthesiologists (ASA) category ≤ 3

         12. Able to comply with study procedures, including the recording of daily questionnaires

        Exclusion Criteria:

          1. Has evidence or history of a coagulopathy or hemostasis problem at Screening or
             Baseline (Day 1)

          2. Treatment knee injections with corticosteroids within 30 days or hyaluronic acid
             within 3 months prior to the procedure

          3. If on opioid analgesics, an upper limit of 30 mg/day of oral morphine sulfate, 20
             mg/day of oxycodone, 30 mg/day of hydrocodone, or 300 mg/day of tramadol, or
             equivalent

          4. Any of the following lab abnormalities within one week of the treatment day:

               -  Platelet count <100,000 cells/mm3

               -  Total neutrophil count <1500 cells/mm3

               -  Serum creatinine ≥ 1.5 x ULN

               -  Alanine aminotransferase (ALT) > 3.0 x ULN

               -  Aspartate aminotransferase (AST) > 3.0 x ULN

               -  Alkaline phosphatase > 2.0 ULN

               -  Bilirubin > 1.5 x ULN

               -  INR > 1.5 x ULN

               -  Temperature ≥ 100.4°F or other evidence of an infection

          5. Concurrent use of opioids for indications other than knee pain

          6. History of substance abuse

          7. Has an allergy or hypersensitivity to chili peppers, capsaicin, resiniferatoxin or
             radiographic contrast agents

          8. Female subjects who are pregnant at Screening or are planning on becoming pregnant, or
             are currently breastfeeding

          9. Subjects with any medical condition or comorbidities that could adversely impact study
             participation or safety, conduct of the study, or interfere with pain assessments

         10. Subjects who have participated in a clinical study of an investigational drug within 4
             half-lives of Screening or are scheduled to receive and investigational agent while
             participating in this study

         11. Sensory peripheral neuropathy that is CTCAE Grade 2 or higher at Screening

         12. Arterial or venous thrombi, myocardial infarction, admission for unstable angina,
             cardiac angioplasty, or stenting within 12 months prior to Screening

         13. Evidence or history of any hemorrhage or bleeding event that is higher than CTCAE
             Grade 1 within 4 weeks prior to injection.

         14. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome-related
             illness, acute or history of chronic hepatitis B or C. Positive tests for HIV-1 or -2
             antibodies, hepatitis B surface antigen, or hepatitis C antibodies.

         15. Concurrent medical or arthritic conditions that could interfere with evaluation of the
             index knee joint including fibromyalgia, rheumatoid arthritis, or other inflammatory
             arthropathies affecting the knee joint

         16. Subjects with significant pain in other joints may be excluded at the discretion of
             the investigator

         17. Subject has undergone arthroscopic or open surgery to the knee within 6 months of the
             planned injection day

         18. Subject has undergone replacement surgery of the treatment knee

         19. Presence of surgical hardware or other foreign bodies in the treatment knee
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 35 Years old.
Subject must be at most 85 Years

Patient description (medical language): A 47-year-old woman comes to the office complaining of pain in the calf and knee when she bends down. The pain limits her activity. Her medical history is significant for osteoarthritis, for which she uses nonsteroidal anti-inflammatory drugs (NSAIDs) for the past two years. She is living with her husband and has 3 children. She doesn't smoke but drinks alcohol occasionally. Her vital signs are normal. On physical examination, there is a small effusion in the right knee. The effusion grew a little larger and she developed a tender swelling in the popliteal fossa and calf. Both the pain and swelling worsened as she bent and straightened her knee.

Patient description (patient's own words): I'm a 47-year-old woman, married with 3 kids. I don't smoke and I drink occasionally. I went to the doctor because of pain in my calf and knee when I was bending down. This has been limiting my daily activities. I have been diagnosed with osteoarthritis for which I have taken anti-inflammatory drugs for the past 2 years. The doctor saw a small fluid buildup in my right knee. This buildup became a bit bigger and I have a swollen calf. The pain is worse when I bend and straighten my knee.

Does the patient match the trial criteria? 1