Study to Evaluate the Iovera° Device for Temporary Relief From Knee Pain

Study Overview
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Brief Summary
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This purpose of this study is to evaluate the effectiveness and safety of the iovera° device for the temporary reduction of pain associated with knee osteoarthritis.

Official Title
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A Multi-Center, Prospective, Double-Blind, Randomized Controlled Study to Evaluate the Effectiveness and Safety of the Iovera° Device for the Temporary Relief of Pain Associated With Knee Osteoarthritis

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Device: iovera°
* Device: Sham Comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 35 - 75 years of age American College of Rheumatology (ACR) criteria for osteoarthritis of the knee. This includes radiographic evidence of osteophytes and at least one of the following: age ≥ 50 years old, morning stiffness ≤ 30 minute duration or crepitus on motion. Grade II or III osteoarthritis of the knee as determined by Kellgren-Lawrence classification grading scale on anteroposterior (AP) x-ray within previous 6 months. Participants are ambulatory without assistive devices. Knee pain of ≥ 40 mm on Visual Analog Scale (VAS) when performing one of two movements that elicit the worst pain: standing from a seated position or walking up/down stairs. Participant reports knee pain in the anterior and/or inferior aspect of the knee as documented on the knee pain map in the appropriate areas. A diagnostic lidocaine (without epinephrine) block of the infrapatellar branch of the saphenous nerve results in a 50% reduction in the VAS pain assessment score when performing the activity that elicits the worst pain: standing from a seated position or walking up/down stairs. Participant is able to tolerate a washout of prescription and over-the-counter pain relief for a duration of 5 times the half-life of the medication prior to the Baseline visit. Participant is able to tolerate a washout of adjunctive therapies for knee pain for 72 hours prior to the Baseline visit. Western Ontario and McMaster Osteoarthritis Index (WOMAC) NRS3.1 Pain subscore ≥ 20 at Baseline/Visit 2. Participant is able to tolerate discontinuation of all pain medication throughout the duration of the study. Acetaminophen may be used as rescue medication with a maximum dose of 4g per day. Participant is able to tolerate discontinuation of rescue medication, acetaminophen, for 24 hours prior to all follow-up visits. Prescription and over-the-counter pain medications must be maintained on a stable schedule for at least two weeks prior to screening. Participant is willing and able to give written informed consent. Participant is willing and able to comply with study instructions and commit to all follow-up visits for the duration of the study. Participant is in good general health and free of any systemic disease state or physical condition that might impair evaluation or which in the Investigator's opinion, exposes the Participant to an unacceptable risk by study participation. Exclusion Criteria: History of a partial or full knee replacement of the knee to be treated. Planned partial or full knee replacement within the next 12 months in knee to be treated. Previous myoscience Focused Cold Therapy^TM (FCTTM) treatment. Viscosupplementation within the previous 6 months in knee to be treated. Participant reports the majority of knee pain outside of the anterior/inferior aspect of the knee. Intra-articular steroid injection in the knee to be treated within previous 3 months. Gross deformity of the knee including varus or valgus. Started physical therapy of the knee to be treated within 3 months of screening. Received acupuncture for knee pain within 3 months prior to screening. Body Mass Index ≥ 35. Prior surgery in the treatment area that may alter the anatomy of the infrapatellar branch of the saphenous nerve or result in scar tissue in the treatment area. Open and/or infected wound in the treatment area. Disease of the spine, hip, contralateral knee or other lower extremity joint of sufficient degree affecting the assessment of the treated knee. Acetaminophen intolerance or allergy. Allergy to lidocaine. History of cryoglobulinemia History of paroxysmal cold hemoglobinuria. History of cold urticaria. History of Raynaud's disease. History of pes anserinus bursitis in the knee to be treated. Use of extended-release or long-acting opioids within previous 3 months. Use of immediate-release opioids for more than 3 days per week within previous month. Participant is pregnant or planning to become pregnant while enrolled in the study. Current enrollment in any investigational drug or device study or participation within 30 days prior to screening. Any additional diagnosis that in the opinion of the Investigator directly contributes to knee pain. Any concomitant inflammatory disease or other condition that affects the joints (e.g. rheumatoid arthritis, metabolic bone disease, gout, active infection, etc.) Any clotting disorder and/or use of an anticoagulant (e.g., aspirin, warfarin, clopidogrel, etc.) within seven (7) days prior to administration of the device. Any local skin condition at the treatment site that in the Investigator's opinion would adversely affect treatment or outcomes. Any chronic medical condition that in the Investigator's opinion would prevent adequate participation. Any chronic medication use (prescription, over-the-counter, etc.) that in the Investigator's opinion would affect study participation or Subject safety. For any reason, in the opinion of the Investigator, the Subject may not be a suitable candidate for study participation (i.e., history of noncompliance, drug dependency, any related knee injury due to a worker's compensation claim, etc.). Known liver dysfunction.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: iovera° Treatment<br>Treatment with the iovera° device administered by a trained investigator to treat knee pain. | Device: iovera°<br> <br> |
| Sham Comparator: Sham Treatment<br>Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain. | Device: Sham Comparator<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale Score at Day 30 | The WOMAC is a tri-dimensional, disease-specific, patient-reported outcome measure. It consists of 24 questions [each question is presented in a numerical rating scale format with possible values between 0= No (best) to 10= Extreme (worst)] with 5 questions regarding pain [possible subscale score 0 to 50], 2 questions regarding stiffness [possible subscale score 0 to 20] and 17 questions regarding function difficulty [possible subscale score 0 to 170]. A negative change from Baseline indicates improvement. An Analysis of Covariance (ANCOVA) model was used for analyses. | Baseline to Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Visual Analog Scale (VAS) at Day 30 | VAS pain assessment is a measure of pain intensity. The scale is made up of a 10 centimeter (cm) [100 millimeter (mm)] horizontal line. The far left of the horizontal line is labeled no pain while the far right of the horizontal line is labeled worst imaginable pain. A negative change from Baseline indicates improvement. An ANCOVA model was used for analyses. | Baseline to Day 30 | 
| Change From Baseline in Total WOMAC Score at Day 30 | The WOMAC is a tri-dimensional, disease-specific, patient-reported outcome measure. It consists of 24 questions [each question is presented in a numerical rating scale format with possible values between 0= No (best) to 10= Extreme (worst)] with 5 questions regarding pain [possible subscale score 0 to 50], 2 questions regarding stiffness [possible subscale score 0 to 20] and 17 questions regarding function difficulty [possible subscale score 0 to 170]. The WOMAC total score was calculated by summing the 3 subscales for a total possible score of 0 to 240. A negative change from Baseline indicates improvement. An ANCOVA model was used for analyses. | Baseline to Day 30 | 
| Change From Baseline in VAS at Day 60 | VAS pain assessment is a measure of pain intensity. The scale is made up of a 10 cm (100 mm) horizontal line. The far left of the horizontal line is labeled no pain while the far right of the horizontal line is labeled worst imaginable pain. A negative change from Baseline indicates improvement. An ANCOVA model was used for analyses. | Baseline to Day 60 | 
| WOMAC Pain Score Responder Rate at Day 30 | WOMAC Pain Score Responder Rate is defined as the percentage of participants with at least a 30% reduction in the WOMAC pain score at Day 30 compared to Baseline. WOMAC is a tri-dimensional, disease-specific, patient-reported outcome measure. It consists of 24 questions [each question is presented in a numerical rating scale format with possible values between 0= No to 10= Extreme] with the first 5 questions regarding pain [possible subscale score 0 (best) to 50 (worst)]. | Day 30 | 
| VAS Responder Rate at Day 30 | VAS Responder Rate is defined as the percentage of participants with at least a 30% reduction in VAS at Day 30 compared to Baseline VAS pain assessment is a measure of pain intensity. The scale is made up of a 10 cm (100 mm) horizontal line. The far left of the horizontal line is labeled no pain while the far right of the horizontal line is labeled worst imaginable pain. | Day 30 | 
| Change From Baseline in Total WOMAC Score at Day 60 | The WOMAC is a tri-dimensional, disease-specific, patient-reported outcome measure. It consists of 24 questions [each question is presented in a numerical rating scale format with possible values between 0= No (best) to 10= Extreme (worst)] with 5 questions regarding pain [possible subscale score 0 to 50], 2 questions regarding stiffness [possible subscale score 0 to 20] and 17 questions regarding function difficulty [possible subscale score 0 to 170]. The WOMAC total score was calculated by summing the 3 subscales for a total possible score of 0 to 240. A negative change from Baseline indicates improvement. | Baseline to Day 60 | 
| VAS Responder Rate at Day 60 | VAS Responder Rate is defined as the percentage of participants with at least a 30% reduction in VAS at Day 60 compared to Baseline. VAS pain assessment is a measure of pain intensity. The scale is made up of a 10 cm (100 mm) horizontal line. The far left of the horizontal line is labeled no pain while the far right of the horizontal line is labeled worst imaginable pain. | Day 60 | 
| WOMAC Pain Score Responder Rate at Day 60 | WOMAC Pain Score Responder Rate is defined as the percentage of participants with at least a 30% reduction in the WOMAC pain score at Day 60 compared to Baseline. WOMAC is a tri-dimensional, disease-specific, patient-reported outcome measure. It consists of 24 questions [each question is presented in a numerical rating scale format with possible values between 0= No (best) to 10= Extreme (worst)] with the first 5 questions regarding pain [possible subscale score 0 to 50]. | Day 60 |