INJECTABLE COLD ENERGY THERAPY FOR THE MANAGEMENT OF CHRONIC PAIN ASSOCIATED WITH OSTEOARTHRITIS OF THE KNEE

Eligibility Criteria

• 1. Age 22 to 80, inclusive of any gender
• 2. Baseline pain intensity of \>/= 5 of the Numeric Rating Scale (NRS) despite current treatment Confidential Brixton Biosciences Inc. Page 12 of 53 Version: 1.1, 30 August 2024
• 3. Chronic symptomatic osteoarthritis of the knee (K-L stage 2, 3, or 4) on plain x-rays obtained within the previous 12 months
• 4. At least 3 months of previous conservative treatments (NSAID, acetaminophen, physical therapy, cortisone injections) that are not currently providing relief
• 5. Agree to see one doctor (study investigator) for knee pain during the study period
• 6. Willing/able to understand the informed consent form and provide written informed consent
• 7. Able to complete outcome measures (including electronic patient reported outcome measures)
• 1. Known allergy to glycerol, hyaluronic acid, poloxamer 407, or phosphate buffered saline
• 2. History of cryoglobulinemia
• 3. History of cold-induced auto-immune hemolytic anemia (e.g. paroxysmal cold hemoglobinuria or cold agglutinin disease)
• 4. History of cold urticaria
• 5. History of Chilblain's (pernio) disease in the lower extremities
• 6. History of Raynaud's disease
• 7. Open and/or infected wounds or active tumor at or near the treatment site
• 8. History of vascular surgery involving femoral vessels on the injection side
• 9. History of surgical procedures to affected limb that, in the opinion of the investigator, could have impacted the integrity of the genicular nerves or blood vessels
• 10. Active bacterial or fungal infection that at the discretion of the investigator would preclude study participation
• 11. Currently taking \>60 MME/day, as determined per MDcalc.com (opioid conversion calculator)
• 12. History of History of systemic inflammatory conditions such as rheumatoid arthritis
• 13. Bleeding disorders anticoagulant therapy, unless appropriately stopped or reversed for the procedure
• 14. Any condition or circumstance that would impact or confound assessment of safety and/or pain. For example, comorbid or concomitant pain conditions, pre-existing lower limb neurologic deficits, any psychiatric or neurologic disease
• 15. Cryoneurolysis, thermal or pulsed radiofrequency ablation, or phenol injection for the index knee within the past 12 months
• 16. Use of intra-articular injection of corticosteroid within the previous 3 months, or hyaluronic acid, prolotherapy, Confidential Brixton Biosciences Inc. Page 13 of 53 Version: 1.1, 30 August 2024 autologous blood, or platelet rich plasma injections for the index knee within the previous 6 months
• 17. Known contraindication to use of a regional anesthetic block
• 18. Pregnant, nursing or intent of becoming pregnant during the study period
• 19. Any condition (such as history of significant cardiovascular, renal failure/dialysis, hepatic or other systemic comorbidity/chronic pain condition) or circumstance that, in the opinion of the investigator, would compromise the safety of the subject or the quality of study data
• 20. Body habitus/knee anatomy that would preclude the use of the product injection needle size
• 21. Participation in any clinical study of a therapeutic investigational product within 30 days prior to enrollment
• 22. Unwilling to refrain from participation in any other clinical study through the duration of this study
• 23. Unwilling to refrain from any scheduled surgeries during the duration of this study