Osteoarthritis, Knee, Pain, Knee
Conditions
Brief summary
This study evaluates the safety of resiniferatoxin in patients with moderate to severe knee pain due to osteoarthritis.
Detailed description
This study is to evaluate the safety of resiniferatoxin administered intra-articularly to subjects with moderate to severe knee pain due to osteoarthritis (OA). It is also to assess the preliminary efficacy of resiniferatoxin to relieve knee pain when walking.
Interventions
DRUGResiniferatoxin
Resiniferatoxin is a compound purified from natural sources.
DRUGSaline
Saline is a normal physiological solution
Sponsors
Sorrento Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Except for the sentinel subject, the treatment assigned to each subject in the dose-escalation cohorts is blinded to the subject, investigators, and sponsor study team. The sentinel subject, the first subject in each dose-escalation cohort, is dosed with resiniferatoxin in an open-label fashion. Subjects in the dose-escalation cohorts who received placebo may receive resiniferatoxin in an open-label fashion after unblinding. All subjects in the dose-expansion cohorts are dosed with resiniferatoxin in an open-label fashion.
Eligibility
Sex/Gender
ALL
Age
35 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety measurement | baseline through week 52 | Incidence and severity of adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement of knee pain when walking | baseline through week 52 | Improvement in pain score versus baseline using the WOMAC Osteoarthritis Index question A1 (pain on walking, 11-point numerical rating scale) |
Countries
United States
Outcome results
None listed