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

INJECTABLE COLD ENERGY THERAPY FOR THE MANAGEMENT OF CHRONIC PAIN ASSOCIATED WITH OSTEOARTHRITIS OF THE KNEE: A MULTI-CENTER, RANDOMIZED, CONTROLLED STUDY (ICE STUDY)

The goal of this clinical trial is to evaluate the effectiveness of Neural Ice for pain management associated with knee osteoarthritis in adults aged 22-80 years. Participants will attend study visits and complete subject diaries. Participants will be followed for 6 months after study procedure.

Study Overview

• Status: Active, not recruiting
• Conditions: Osteoarthritis (OA) of the Knee
• Intervention / Treatment: Device: Neural Ice; Drug: Triamcinolone acetate

• Study Type: Interventional
• Enrollment (Estimated): 263
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Larkspur, California, United States, 94939
      • Marin Health
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20036
      • Centers for Advanced Orthopedics
  • Florida
    • Gainesville, Florida, United States, 32607
      • The Orthopaedic Institute
  • Georgia
    • Johns Creek, Georgia, United States, 30097
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60616
      • Insight Hospital and Medical Center Chicago
  • Kansas
    • Wichita, Kansas, United States, 67226
      • NextStage Clinical Research Advanced Orthopaedic Associates
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Ochsner Health System
  • Maryland
    • North Bethesda, Maryland, United States, 20852
      • NextStage Clinical Research Regenerative Orthopedics and Sports Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Flint, Michigan, United States, 48507
      • Insight Research Institute
  • Oklahoma
    • Edmond, Oklahoma, United States, 73034
      • Clinical Investigations, LLC
    • Tulsa, Oklahoma, United States, 74104
      • NextStage Clinical Research The Orthopedic Center
  • Pennsylvania
    • Sewickley, Pennsylvania, United States, 15143
      • Pain Diagnostics and Interventional Care
  • Texas
    • Houston, Texas, United States, 77058
      • NextStage Clinical Research All-American Orthopedic & Sports Medicine Institute
    • San Antonio, Texas, United States, 78229
      • UT San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion 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)

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neural Ice injections; This therapy will be injected around the superolateral, superomedial, and inferomedial genicular nerves.	Device: Neural Ice; This therapy will be injected around the superolateral, superomedial, and inferomedial genicular nerves.
Active Comparator: Corticosteroid injection; Intraarticular corticosteroid injection is defined as a single dose of Triamcinolone 40mg injected directly into the joint space.	Drug: Triamcinolone acetate; A single dose of Triamcinolone 40mg injected directly into the joint space.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Effectiveness	The proportion of subjects whose knee pain following activity (Timed Up and Go test) is reduced by ≥30% based on the NRS scale at 3 months post treatment.	3 months
Primary Safety	Aggregate serious device-related adverse events through final follow up visit.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Effectiveness	The proportion of subjects whose knee pain following activity (Timed Up and Go test) is reduced by ≥30% based on the NRS scale at 6 months post treatment.	6 months
NRS Scores		6 months
Pain medication usage		6 months
PGIC scores		6 months
KOOS, JR scores		6 months
Onset of pain relief defined as pain reduced by 30% based on NRS score from baseline		6 months
Change in Timed-Up and Go (TUG) test scores from baseline		6 months

Other Outcome Measures

Outcome Measure	Time Frame
Patient-Specific Functional Scale (PSFS)	6 months
Knee procedures specific Healthcare Utilization Data	6 months
EQ-5D-5L Global Quality of Life measure	6 months

Collaborators and Investigators

• Sponsor: Brixton Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: November 19, 2024
• First Submitted That Met QC Criteria: November 19, 2024
• First Posted (Actual): November 21, 2024

Study Record Updates

• Last Update Posted (Estimated): October 28, 2025
• Last Update Submitted That Met QC Criteria: October 27, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: osteoarthritis; knee osteoarthritis; knee pain; osteoarthritis of the knee
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Triamcinolone
• Other Study ID Numbers: BXT-786-KPM-03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No