<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02260921</url>
  </required_header>
  <id_info>
    <org_study_id>MYO-0946</org_study_id>
    <nct_id>NCT02260921</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Iovera° Device for Temporary Relief From Knee Pain</brief_title>
  <official_title>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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pacira CryoTech, Inc., a wholly owned subsidiary of Pacira BioSciences, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pacira CryoTech, Inc., a wholly owned subsidiary of Pacira BioSciences, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This purpose of this study is to evaluate the effectiveness and safety of the iovera° device&#xD;
      for the temporary reduction of pain associated with knee osteoarthritis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 20, 2014</start_date>
  <completion_date type="Actual">May 31, 2016</completion_date>
  <primary_completion_date type="Actual">February 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Absolute Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale Score at Day 30</measure>
    <time_frame>Baseline to Day 30</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Visual Analog Scale (VAS) at Day 30</measure>
    <time_frame>Baseline to Day 30</time_frame>
    <description>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 &quot;no pain&quot; while the far right of the horizontal line is labeled &quot;worst imaginable pain&quot;. A negative change from Baseline indicates improvement. An ANCOVA model was used for analyses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Total WOMAC Score at Day 30</measure>
    <time_frame>Baseline to Day 30</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in VAS at Day 60</measure>
    <time_frame>Baseline to Day 60</time_frame>
    <description>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 &quot;no pain&quot; while the far right of the horizontal line is labeled &quot;worst imaginable pain&quot;. A negative change from Baseline indicates improvement. An ANCOVA model was used for analyses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WOMAC Pain Score Responder Rate at Day 30</measure>
    <time_frame>Day 30</time_frame>
    <description>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)].</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>VAS Responder Rate at Day 30</measure>
    <time_frame>Day 30</time_frame>
    <description>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 &quot;no pain&quot; while the far right of the horizontal line is labeled &quot;worst imaginable pain&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Total WOMAC Score at Day 60</measure>
    <time_frame>Baseline to Day 60</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>VAS Responder Rate at Day 60</measure>
    <time_frame>Day 60</time_frame>
    <description>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 &quot;no pain&quot; while the far right of the horizontal line is labeled &quot;worst imaginable pain&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WOMAC Pain Score Responder Rate at Day 60</measure>
    <time_frame>Day 60</time_frame>
    <description>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].</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">180</enrollment>
  <condition>Knee Osteoarthritis</condition>
  <arm_group>
    <arm_group_label>iovera° Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment with the iovera° device administered by a trained investigator to treat knee pain.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham Treatment</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>iovera°</intervention_name>
    <arm_group_label>iovera° Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham Comparator</intervention_name>
    <arm_group_label>Sham Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  35 - 75 years of age&#xD;
&#xD;
          -  American College of Rheumatology (ACR) criteria for osteoarthritis of the knee. This&#xD;
             includes radiographic evidence of osteophytes and at least one of the following: age ≥&#xD;
             50 years old, morning stiffness ≤ 30 minute duration or crepitus on motion.&#xD;
&#xD;
          -  Grade II or III osteoarthritis of the knee as determined by Kellgren-Lawrence&#xD;
             classification grading scale on anteroposterior (AP) x-ray within previous 6 months.&#xD;
&#xD;
          -  Participants are ambulatory without assistive devices.&#xD;
&#xD;
          -  Knee pain of ≥ 40 mm on Visual Analog Scale (VAS) when performing one of two movements&#xD;
             that elicit the worst pain: standing from a seated position or walking up/down stairs.&#xD;
&#xD;
          -  Participant reports knee pain in the anterior and/or inferior aspect of the knee as&#xD;
             documented on the knee pain map in the appropriate areas.&#xD;
&#xD;
          -  A diagnostic lidocaine (without epinephrine) block of the infrapatellar branch of the&#xD;
             saphenous nerve results in a 50% reduction in the VAS pain assessment score when&#xD;
             performing the activity that elicits the worst pain: standing from a seated position&#xD;
             or walking up/down stairs.&#xD;
&#xD;
          -  Participant is able to tolerate a washout of prescription and over-the-counter pain&#xD;
             relief for a duration of 5 times the half-life of the medication prior to the Baseline&#xD;
             visit.&#xD;
&#xD;
        Participant is able to tolerate a washout of adjunctive therapies for knee pain for 72&#xD;
        hours prior to the Baseline visit.&#xD;
&#xD;
          -  Western Ontario and McMaster Osteoarthritis Index (WOMAC) NRS3.1 Pain subscore ≥ 20 at&#xD;
             Baseline/Visit 2.&#xD;
&#xD;
          -  Participant is able to tolerate discontinuation of all pain medication throughout the&#xD;
             duration of the study. Acetaminophen may be used as rescue medication with a maximum&#xD;
             dose of 4g per day.&#xD;
&#xD;
          -  Participant is able to tolerate discontinuation of rescue medication, acetaminophen,&#xD;
             for 24 hours prior to all follow-up visits.&#xD;
&#xD;
          -  Prescription and over-the-counter pain medications must be maintained on a stable&#xD;
             schedule for at least two weeks prior to screening.&#xD;
&#xD;
          -  Participant is willing and able to give written informed consent.&#xD;
&#xD;
          -  Participant is willing and able to comply with study instructions and commit to all&#xD;
             follow-up visits for the duration of the study.&#xD;
&#xD;
          -  Participant is in good general health and free of any systemic disease state or&#xD;
             physical condition that might impair evaluation or which in the Investigator's&#xD;
             opinion, exposes the Participant to an unacceptable risk by study participation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of a partial or full knee replacement of the knee to be treated.&#xD;
&#xD;
          -  Planned partial or full knee replacement within the next 12 months in knee to be&#xD;
             treated.&#xD;
&#xD;
          -  Previous myoscience Focused Cold Therapy^TM (FCTTM) treatment.&#xD;
&#xD;
          -  Viscosupplementation within the previous 6 months in knee to be treated.&#xD;
&#xD;
          -  Participant reports the majority of knee pain outside of the anterior/inferior aspect&#xD;
             of the knee.&#xD;
&#xD;
          -  Intra-articular steroid injection in the knee to be treated within previous 3 months.&#xD;
&#xD;
          -  Gross deformity of the knee including varus or valgus.&#xD;
&#xD;
          -  Started physical therapy of the knee to be treated within 3 months of screening.&#xD;
&#xD;
          -  Received acupuncture for knee pain within 3 months prior to screening.&#xD;
&#xD;
          -  Body Mass Index ≥ 35.&#xD;
&#xD;
          -  Prior surgery in the treatment area that may alter the anatomy of the infrapatellar&#xD;
             branch of the saphenous nerve or result in scar tissue in the treatment area.&#xD;
&#xD;
          -  Open and/or infected wound in the treatment area.&#xD;
&#xD;
          -  Disease of the spine, hip, contralateral knee or other lower extremity joint of&#xD;
             sufficient degree affecting the assessment of the treated knee.&#xD;
&#xD;
          -  Acetaminophen intolerance or allergy.&#xD;
&#xD;
          -  Allergy to lidocaine.&#xD;
&#xD;
          -  History of cryoglobulinemia&#xD;
&#xD;
          -  History of paroxysmal cold hemoglobinuria.&#xD;
&#xD;
          -  History of cold urticaria.&#xD;
&#xD;
          -  History of Raynaud's disease.&#xD;
&#xD;
          -  History of pes anserinus bursitis in the knee to be treated.&#xD;
&#xD;
          -  Use of extended-release or long-acting opioids within previous 3 months.&#xD;
&#xD;
          -  Use of immediate-release opioids for more than 3 days per week within previous month.&#xD;
&#xD;
          -  Participant is pregnant or planning to become pregnant while enrolled in the study.&#xD;
&#xD;
          -  Current enrollment in any investigational drug or device study or participation within&#xD;
             30 days prior to screening.&#xD;
&#xD;
          -  Any additional diagnosis that in the opinion of the Investigator directly contributes&#xD;
             to knee pain.&#xD;
&#xD;
          -  Any concomitant inflammatory disease or other condition that affects the joints (e.g.&#xD;
             rheumatoid arthritis, metabolic bone disease, gout, active infection, etc.)&#xD;
&#xD;
          -  Any clotting disorder and/or use of an anticoagulant (e.g., aspirin, warfarin,&#xD;
             clopidogrel, etc.) within seven (7) days prior to administration of the device.&#xD;
&#xD;
          -  Any local skin condition at the treatment site that in the Investigator's opinion&#xD;
             would adversely affect treatment or outcomes.&#xD;
&#xD;
          -  Any chronic medical condition that in the Investigator's opinion would prevent&#xD;
             adequate participation.&#xD;
&#xD;
          -  Any chronic medication use (prescription, over-the-counter, etc.) that in the&#xD;
             Investigator's opinion would affect study participation or Subject safety.&#xD;
&#xD;
          -  For any reason, in the opinion of the Investigator, the Subject may not be a suitable&#xD;
             candidate for study participation (i.e., history of noncompliance, drug dependency,&#xD;
             any related knee injury due to a worker's compensation claim, etc.).&#xD;
&#xD;
          -  Known liver dysfunction.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Medvin Clinical Research</name>
      <address>
        <city>Covina</city>
        <state>California</state>
        <zip>91723</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC Davis Center for Musculoskeletal Health</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Coastal Orthopedics and Sports Medicine of Southwest Florida, PA</name>
      <address>
        <city>Bradenton</city>
        <state>Florida</state>
        <zip>34203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shrock Orthpedic Research</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33316</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Health Awareness</name>
      <address>
        <city>Jupiter</city>
        <state>Florida</state>
        <zip>33458</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>JM Clinical Research</name>
      <address>
        <city>South Miami</city>
        <state>Florida</state>
        <zip>33143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Injury Care Medical Center</name>
      <address>
        <city>Boise</city>
        <state>Idaho</state>
        <zip>83713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rockford Orthopedic Associates, LTD</name>
      <address>
        <city>Rockford</city>
        <state>Illinois</state>
        <zip>61114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kansas University Medical Center</name>
      <address>
        <city>Fairway</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kansas City Bone and Joint Clinic</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Covington Orthopedic and Sports Medicine Institute</name>
      <address>
        <city>Covington</city>
        <state>Louisiana</state>
        <zip>70433</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LHU HSC Department of Orthopaedics</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arthritis Treatment Center</name>
      <address>
        <city>Frederick</city>
        <state>Maryland</state>
        <zip>21702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Triangle Orthopaedic Associates, P.A.</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Blair Orthopedic Associates, Inc.</name>
      <address>
        <city>Altoona</city>
        <state>Pennsylvania</state>
        <zip>16602</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PCET Research Center</name>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <zip>37909</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spokane Joint Replacement Center</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>October 3, 2014</study_first_submitted>
  <study_first_submitted_qc>October 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 9, 2014</study_first_posted>
  <results_first_submitted>June 6, 2019</results_first_submitted>
  <results_first_submitted_qc>December 7, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">December 31, 2020</results_first_posted>
  <last_update_submitted>January 19, 2021</last_update_submitted>
  <last_update_submitted_qc>January 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
    <mesh_term>Osteoarthritis, Knee</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Iovera° Treatment</title>
          <description>Treatment with the iovera° device administered by a trained investigator to treat knee pain.</description>
        </group>
        <group group_id="P2">
          <title>Sham Treatment</title>
          <description>Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="121"/>
                <participants group_id="P2" count="59"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Per-Protocol Population</title>
              <participants_list>
                <participants group_id="P1" count="112"/>
                <participants group_id="P2" count="56"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="107"/>
                <participants group_id="P2" count="55"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdraw Consent</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Prohibited Treatment for Knee Pain</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intent-to-treat (ITT) Analysis Population include all randomized participants who underwent the assigned treatment.</population>
      <group_list>
        <group group_id="B1">
          <title>Iovera° Treatment</title>
          <description>Treatment with the iovera° device administered by a trained investigator to treat knee pain.</description>
        </group>
        <group group_id="B2">
          <title>Sham Treatment</title>
          <description>Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="121"/>
            <count group_id="B2" value="59"/>
            <count group_id="B3" value="180"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="60.7" lower_limit="36.5" upper_limit="75.3"/>
                    <measurement group_id="B2" value="61.3" lower_limit="40.3" upper_limit="74.7"/>
                    <measurement group_id="B3" value="61.0" lower_limit="36.5" upper_limit="75.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="79"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="119"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="110"/>
                    <measurement group_id="B2" value="50"/>
                    <measurement group_id="B3" value="160"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="121"/>
                    <measurement group_id="B2" value="59"/>
                    <measurement group_id="B3" value="180"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (BMI)</title>
          <units>kg/m^2</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29.02" lower_limit="18.6" upper_limit="41.4"/>
                    <measurement group_id="B2" value="29.99" lower_limit="20.3" upper_limit="35.5"/>
                    <measurement group_id="B3" value="29.5" lower_limit="18.6" upper_limit="41.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Absolute Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale Score at Day 30</title>
        <description>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.</description>
        <time_frame>Baseline to Day 30</time_frame>
        <population>Per-protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Iovera° Treatment</title>
            <description>Treatment with the iovera° device administered by a trained investigator to treat knee pain.</description>
          </group>
          <group group_id="O2">
            <title>Sham Treatment</title>
            <description>Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.</description>
          </group>
        </group_list>
        <measure>
          <title>Absolute Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale Score at Day 30</title>
          <description>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.</description>
          <population>Per-protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="56"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-16.33" spread="1.15"/>
                    <measurement group_id="O2" value="-8.79" spread="1.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0002</p_value>
            <p_value_desc>P-values are obtained by fitting an ANCOVA model with treatment as factor and WOMAC baseline pain score as a covariate.</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Difference in Least Squares (LS) Means</param_type>
            <param_value>-7.53</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-11.48</ci_lower_limit>
            <ci_upper_limit>-3.58</ci_upper_limit>
            <estimate_desc>LS estimates are obtained by fitting an ANCOVA model with treatment as factor and WOMAC baseline pain score as a covariate.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Visual Analog Scale (VAS) at Day 30</title>
        <description>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 &quot;no pain&quot; while the far right of the horizontal line is labeled &quot;worst imaginable pain&quot;. A negative change from Baseline indicates improvement. An ANCOVA model was used for analyses.</description>
        <time_frame>Baseline to Day 30</time_frame>
        <population>Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Iovera° Treatment</title>
            <description>Treatment with the iovera° device administered by a trained investigator to treat knee pain.</description>
          </group>
          <group group_id="O2">
            <title>Sham Treatment</title>
            <description>Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Visual Analog Scale (VAS) at Day 30</title>
          <description>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 &quot;no pain&quot; while the far right of the horizontal line is labeled &quot;worst imaginable pain&quot;. A negative change from Baseline indicates improvement. An ANCOVA model was used for analyses.</description>
          <population>Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="56"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-39.20" spread="2.74"/>
                    <measurement group_id="O2" value="-25.70" spread="3.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Total WOMAC Score at Day 30</title>
        <description>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.</description>
        <time_frame>Baseline to Day 30</time_frame>
        <population>Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Iovera° Treatment</title>
            <description>Treatment with the iovera° device administered by a trained investigator to treat knee pain.</description>
          </group>
          <group group_id="O2">
            <title>Sham Treatment</title>
            <description>Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Total WOMAC Score at Day 30</title>
          <description>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.</description>
          <population>Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="56"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-77.18" spread="5.38"/>
                    <measurement group_id="O2" value="-43.77" spread="7.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in VAS at Day 60</title>
        <description>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 &quot;no pain&quot; while the far right of the horizontal line is labeled &quot;worst imaginable pain&quot;. A negative change from Baseline indicates improvement. An ANCOVA model was used for analyses.</description>
        <time_frame>Baseline to Day 60</time_frame>
        <population>Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Iovera° Treatment</title>
            <description>Treatment with the iovera° device administered by a trained investigator to treat knee pain.</description>
          </group>
          <group group_id="O2">
            <title>Sham Treatment</title>
            <description>Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in VAS at Day 60</title>
          <description>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 &quot;no pain&quot; while the far right of the horizontal line is labeled &quot;worst imaginable pain&quot;. A negative change from Baseline indicates improvement. An ANCOVA model was used for analyses.</description>
          <population>Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="56"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-37.46" spread="2.80"/>
                    <measurement group_id="O2" value="-28.82" spread="3.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>WOMAC Pain Score Responder Rate at Day 30</title>
        <description>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)].</description>
        <time_frame>Day 30</time_frame>
        <population>Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Iovera° Treatment</title>
            <description>Treatment with the iovera° device administered by a trained investigator to treat knee pain.</description>
          </group>
          <group group_id="O2">
            <title>Sham Treatment</title>
            <description>Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.</description>
          </group>
        </group_list>
        <measure>
          <title>WOMAC Pain Score Responder Rate at Day 30</title>
          <description>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)].</description>
          <population>Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="56"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.9"/>
                    <measurement group_id="O2" value="44.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>VAS Responder Rate at Day 30</title>
        <description>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 &quot;no pain&quot; while the far right of the horizontal line is labeled &quot;worst imaginable pain&quot;.</description>
        <time_frame>Day 30</time_frame>
        <population>Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Iovera° Treatment</title>
            <description>Treatment with the iovera° device administered by a trained investigator to treat knee pain.</description>
          </group>
          <group group_id="O2">
            <title>Sham Treatment</title>
            <description>Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.</description>
          </group>
        </group_list>
        <measure>
          <title>VAS Responder Rate at Day 30</title>
          <description>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 &quot;no pain&quot; while the far right of the horizontal line is labeled &quot;worst imaginable pain&quot;.</description>
          <population>Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="56"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.9"/>
                    <measurement group_id="O2" value="48.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Total WOMAC Score at Day 60</title>
        <description>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.</description>
        <time_frame>Baseline to Day 60</time_frame>
        <population>Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Iovera° Treatment</title>
            <description>Treatment with the iovera° device administered by a trained investigator to treat knee pain.</description>
          </group>
          <group group_id="O2">
            <title>Sham Treatment</title>
            <description>Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Total WOMAC Score at Day 60</title>
          <description>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.</description>
          <population>Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="56"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-70.50" spread="5.52"/>
                    <measurement group_id="O2" value="-49.99" spread="7.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>VAS Responder Rate at Day 60</title>
        <description>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 &quot;no pain&quot; while the far right of the horizontal line is labeled &quot;worst imaginable pain&quot;.</description>
        <time_frame>Day 60</time_frame>
        <population>Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Iovera° Treatment</title>
            <description>Treatment with the iovera° device administered by a trained investigator to treat knee pain.</description>
          </group>
          <group group_id="O2">
            <title>Sham Treatment</title>
            <description>Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.</description>
          </group>
        </group_list>
        <measure>
          <title>VAS Responder Rate at Day 60</title>
          <description>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 &quot;no pain&quot; while the far right of the horizontal line is labeled &quot;worst imaginable pain&quot;.</description>
          <population>Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="56"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65.2"/>
                    <measurement group_id="O2" value="55.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>WOMAC Pain Score Responder Rate at Day 60</title>
        <description>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].</description>
        <time_frame>Day 60</time_frame>
        <population>Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Iovera° Treatment</title>
            <description>Treatment with the iovera° device administered by a trained investigator to treat knee pain.</description>
          </group>
          <group group_id="O2">
            <title>Sham Treatment</title>
            <description>Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.</description>
          </group>
        </group_list>
        <measure>
          <title>WOMAC Pain Score Responder Rate at Day 60</title>
          <description>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].</description>
          <population>Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="56"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64.3"/>
                    <measurement group_id="O2" value="48.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>6 Months</time_frame>
      <desc>Adverse Event (AE) data was collected over a 6 month period. Patients were followed until AE's were resolved.</desc>
      <group_list>
        <group group_id="E1">
          <title>Iovera° Treatment</title>
          <description>Treatment with the iovera° device administered by a trained investigator to treat knee pain.</description>
        </group>
        <group group_id="E2">
          <title>Sham Treatment</title>
          <description>Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title vocab="MedDRA LLT">Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Lung neoplasm malignant</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="121" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="59" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title vocab="MedDRA LLT">Administration site bruise</sub_title>
                <counts group_id="E1" subjects_affected="93" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="31" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title vocab="MedDRA LLT">Administration site dysaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Administration site pain</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Administration site paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Administration site scab</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Administration site swelling</sub_title>
                <counts group_id="E1" subjects_affected="49" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Application site discolouration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Application site pruritus</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Application site hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="63" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="32" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Application site erythema</sub_title>
                <counts group_id="E1" subjects_affected="50" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Application site pain</sub_title>
                <counts group_id="E1" subjects_affected="46" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director of Clinical</name_or_title>
      <organization>Myoscience</organization>
      <phone>5109331541</phone>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02260921
org study id: MYO-0946
nct id: NCT02260921
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Absolute Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale Score at Day 30
time frame: Baseline to Day 30
description: 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.
measure: Change From Baseline in Visual Analog Scale (VAS) at Day 30
time frame: Baseline to Day 30
description: 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.
measure: Change From Baseline in Total WOMAC Score at Day 30
time frame: Baseline to Day 30
description: 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.
measure: Change From Baseline in VAS at Day 60
time frame: Baseline to Day 60
description: 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.
measure: WOMAC Pain Score Responder Rate at Day 30
time frame: Day 30
description: 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)].
measure: VAS Responder Rate at Day 30
time frame: Day 30
description: 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".
measure: Change From Baseline in Total WOMAC Score at Day 60
time frame: Baseline to Day 60
description: 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.
measure: VAS Responder Rate at Day 60
time frame: Day 60
description: 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".
measure: WOMAC Pain Score Responder Rate at Day 60
time frame: Day 60
description: 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].
arm group label: iovera° Treatment
arm group type: Experimental
description: Treatment with the iovera° device administered by a trained investigator to treat knee pain.
arm group label: Sham Treatment
arm group type: Sham Comparator
description: Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.
intervention type: Device
intervention name: iovera°
arm group label: iovera° Treatment
intervention type: Device
intervention name: Sham Comparator
arm group label: Sham Treatment
criteria: 
gender: All
minimum age: 35 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
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country: United States
responsible party type: Sponsor
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 