<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/NCT02987205</url>
  </required_header>
  <id_info>
    <org_study_id>SYM2014-02</org_study_id>
    <nct_id>NCT02987205</nct_id>
  </id_info>
  <brief_title>Multicenter Double-Blind Randomized Split-Face Study to Evaluate Revanesse® Ultra vs Restylane® for Correction of NLF</brief_title>
  <official_title>A Multicenter, Double-Blind, Randomized, Split-Face Study to Evaluate the Safety and Efficacy of Revanesse® Ultra Versus Restylane® for the Correction of Nasolabial Folds</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Prollenium Medical Technologies Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Prollenium Medical Technologies Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A randomized, multicenter, double blind, split-face study in subjects seeking NLF correction.&#xD;
      Subjects were treated with Revanesse Ultra in the NLF on one side of the face and Restylane&#xD;
      in the NLF on the other side of the face. The side of the face for each product was randomly&#xD;
      assigned. The investigator performing the evaluations and the subject were blinded to the&#xD;
      treatment; injections of the study product were performed by an unblinded injecting&#xD;
      investigator.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study was a randomized, double-blind prospective, comparative study of the efficacy and&#xD;
      safety of Revanesse Ultra versus the approved product Restylane in the cutaneous correction&#xD;
      of NLFs. Randomization followed a 1:1 within-subject control model of augmentation correction&#xD;
      of NLFs. Given that the implants have been shown to not migrate, the within-subject model was&#xD;
      ideal and had already been shown in previous studies to detect differences. Subjects with&#xD;
      signs of NLFs who met the entry criteria were enrolled. All subjects were followed for&#xD;
      efficacy and safety for 6 months. Subjects could have open-label retreatment as needed with&#xD;
      Revanesse Ultra at 6 months if their baseline WSRS scores had returned to baseline, or as&#xD;
      needed to achieve optimal correction if their baseline WSRS scores had not returned to&#xD;
      baseline and were followed for a total of 12 months. The study design was appropriate for the&#xD;
      indication studied.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2015</start_date>
  <completion_date type="Actual">September 2016</completion_date>
  <primary_completion_date type="Actual">March 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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary Efficacy Variable is Change From Baseline to Visit 6/Week 24 in Wrinkle Severity Rating Scale (WSRS) Score</measure>
    <time_frame>Visit 6/Week 24</time_frame>
    <description>Primary efficacy variable is change from Baseline to Visit 6/Week 24 in Wrinkle Severity Rating Scale (WSRS) - Treatment success is defined as at least a 1-grade improvement in WSRS from baseline to Week 24&#xD;
WSRS Score categories:&#xD;
Absent - No visible fold; continuous skin line.&#xD;
Mild - Shallow but visible fold with a slight indentation; minor facial feature; implant is expected to produce a slight improvement in appearance.&#xD;
Moderate - Moderately deep folds; clear facial feature visible at normal appearance but not when stretched; excellent correction is expected from injectable implant.&#xD;
Severe - Very long and deep folds; prominent facial feature; less than 2 mm visible when stretched; significant improvement is expected from injectable implant.&#xD;
Extreme - Extremely deep and long folds, detrimental to facial appearance; 2 to 4 mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints Are the Responder Rate, Percentage of *Nasolabial Folds* With Treatment Success</measure>
    <time_frame>Visit 6/Week 24</time_frame>
    <description>Treatment success (defined as at least a 1-grade improvement in WSRS from baseline to Week 24):&#xD;
The WSRS Score is a 5-point scale. The WSRS score was assessed for each NLF at every study visit through Visit 6/Week 24 by a blinded evaluator (blinded to the treatment assignment of each NLF).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Other Efficacy Variables Include Change in WSRS Score</measure>
    <time_frame>Visit 2/Week 1, Visit 3/Week 2, Visit 4/Week 4, and Visit 5/Week 12</time_frame>
    <description>Treatment success is (defined as at least a 1-grade improvement in WSRS from baseline to Week 24)</description>
  </other_outcome>
  <other_outcome>
    <measure>Other Efficacy Variables Include Change in Patient Global Aesthetic Improvement (pGAI) Score</measure>
    <time_frame>Visit 2/Week 1, Visit 3/Week 2, Visit 4/Week 4, and Visit 5/Week 12</time_frame>
    <description>Treatment success is (defined as at least a 1-grade improvement in WSRS from baseline to Week 24)</description>
  </other_outcome>
  <other_outcome>
    <measure>Other Efficacy Variables Include Change in Investigator Global Aesthetic Improvement (iGAI) Score</measure>
    <time_frame>Visit 2/Week 1, Visit 3/Week 2, Visit 4/Week 4, and Visit 5/Week 12</time_frame>
    <description>Treatment success is (defined as at least a 1-grade improvement in WSRS from baseline to Week 24)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">163</enrollment>
  <condition>Nasolabial Fold Correction</condition>
  <arm_group>
    <arm_group_label>Revanesse Ultra</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Revanesse Ultra in the NLF on one side of the face</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Restylane</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Restylane injection in the NLF on the other side of the face to optimal correction</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Revanesse Ultra</intervention_name>
    <description>NLF correction</description>
    <arm_group_label>Revanesse Ultra</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Restylane</intervention_name>
    <description>NLF Correction</description>
    <arm_group_label>Restylane</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subjects must meet all of the following criteria to be eligible for the study:&#xD;
&#xD;
          1. Men or women 22 years of age or older.&#xD;
&#xD;
          2. Two fully visible bilateral nasolabial folds each with a Wrinkle Severity Rating Scale&#xD;
             Score of 3 or 4 that may be corrected with an injectable dermal filler.&#xD;
&#xD;
          3. If female and of childbearing potential, a negative urine pregnancy test and agree to&#xD;
             use adequate contraception. Female subjects of childbearing potential (excluding women&#xD;
             who are surgically sterilized or postmenopausal for at least 2 years) must have a&#xD;
             negative urine pregnancy test and must be willing to use a medically accepted method&#xD;
             of contraception during the study. The following are considered acceptable methods of&#xD;
             birth control for the purpose of this study: oral contraceptives, contraceptive&#xD;
             patches, contraceptive implant, vaginal contraceptive, double barrier methods (e.g.,&#xD;
             condom and spermicide), contraceptive injection (Depo-Provera®), intrauterine device&#xD;
             (IUD), hormonal IUD (Mirena®), and abstinence with a documented second acceptable&#xD;
             method of birth control if the subject becomes sexually active. Subjects entering the&#xD;
             study who are on hormonal contraceptives must have been on the method for at least 90&#xD;
             days prior to the study and continue the method for the duration of the study.&#xD;
             Subjects who had used hormonal contraception and stopped must have stopped no less&#xD;
             than 90 days prior to Visit 1/Day 1.&#xD;
&#xD;
          4. Ability to understand and comply with the requirements of the study.&#xD;
&#xD;
          5. Willingness and ability to provide written informed consent.&#xD;
&#xD;
          6. Agree to refrain from seeking other treatment for this condition during the study.&#xD;
&#xD;
             -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects who meet any of the following criteria will be excluded from the study:&#xD;
&#xD;
          1. Wrinkle Severity Rating Scale Score of ≤ 2 on the right or left nasolabial fold.&#xD;
&#xD;
          2. Women who are pregnant or lactating.&#xD;
&#xD;
          3. Received prior dermabrasion, facelift, or Botox below the orbital rim within 6 months&#xD;
             (180 days) prior to entry into the study.&#xD;
&#xD;
          4. Previous tissue augmentation (bulking agents) for facial wrinkles and scars within 6&#xD;
             months (180 days) at the proposed injection sites.&#xD;
&#xD;
          5. Previous tissue augmentation with permanent implants.&#xD;
&#xD;
          6. Evidence of scar-related disease or delayed healing activity within the past 1 year.&#xD;
&#xD;
          7. Scars at the intended treatment sites.&#xD;
&#xD;
          8. History of keloid formation or hypertrophic scars.&#xD;
&#xD;
          9. Any infection or wound on the face.&#xD;
&#xD;
         10. Allergic history including anaphylaxis or multiple severe allergies to natural rubber&#xD;
             latex or lidocaine.&#xD;
&#xD;
         11. Aspirin or nonsteroidal anti-inflammatory drugs within 1 week (7 days) prior to&#xD;
             treatment.&#xD;
&#xD;
         12. Concomitant anticoagulant therapy, antiplatelet therapy, or history of bleeding&#xD;
             disorders or connective tissue disorders.&#xD;
&#xD;
         13. Over-the-counter (OTC) wrinkle products or prescription wrinkle treatments within 4&#xD;
             weeks (28 days) prior to treatment and throughout the study.&#xD;
&#xD;
         14. Immunocompromised or immunosuppressed.&#xD;
&#xD;
         15. Clinically significant organic disease including clinically significant&#xD;
             cardiovascular, hepatic, pulmonary, neurologic, or renal disease or other medical&#xD;
             condition, serious intercurrent illness, or extenuating circumstance that, in the&#xD;
             opinion of the investigator, preclude participation in the trial.&#xD;
&#xD;
         16. Received any investigational product within 30 days of signing the Informed Consent&#xD;
             Form.&#xD;
&#xD;
         17. Facial tattoo that may interfere with diagnosis.&#xD;
&#xD;
         18. Systemic (oral/injectable) corticosteroids or immunosuppressive medications within 30&#xD;
             days prior to treatment and topical steroids on the face within 14 days prior to&#xD;
             treatment start and throughout the study.&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>22 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael H Gold, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tennessee Clinical Research Center</affiliation>
  </overall_official>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>December 5, 2016</study_first_submitted>
  <study_first_submitted_qc>December 6, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 8, 2016</study_first_posted>
  <results_first_submitted>August 25, 2017</results_first_submitted>
  <results_first_submitted_qc>November 14, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">December 13, 2017</results_first_posted>
  <last_update_submitted>January 24, 2018</last_update_submitted>
  <last_update_submitted_qc>January 24, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 22, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 28, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/05/NCT02987205/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Bilateral Treatment With Revanesse Ultra and Restylane</title>
          <description>Randomized treatment with Revanesse Ultra in the Nasolabial Fold (NLF) on one side of the face, and Restylane on the opposite side of the face - the study is a randomized, multicenter, double blind, split-face study in subjects seeking NLF correction. Subjects were treated with Revanesse Ultra in the NLF on one side of the face and Restylane in the NLF on the other side of the face. The side of the face for each product was randomly assigned.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="163"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated - Bilateral NLF Injection</title>
              <participants_list>
                <participants group_id="P1" count="163"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="159">Treatment is bilateral, subject lost to Restylane AE was lost to further Revanesse Ultra treatment</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" 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_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>There were 163 participants enrolled and treated, the participants received bilateral NLF injection with Revanesse Ultra in one NLF, and Restylane in the other NLF</population>
      <group_list>
        <group group_id="B1">
          <title>Split Face Study Bilateral Revanesse Ultra vs Restylane in NLF</title>
          <description>Split face study - Revanesse Ultra in the NLF on one side of the face and Restylane on the opposite side of the face for NLF correction, treatment is randomized</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="163"/>
          </count_list>
        </analyzed>
        <analyzed>
          <units>NLF Treatments</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="326"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55.4" spread="10.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <title>22 to &lt;40 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>40 to &lt;64 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="110"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>64 to &lt;75 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>= or &gt;75 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="156"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="146"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="154"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Fitzpatrick Skin Type (FST) Classification</title>
          <description>FST Type I skin always burns, never tans (pale white; blond or red hair; blue, gray eyes; freckles) FST Type II skin usually burns, tans minimally (white; blond, brown or red hair; blue, green, or hazel eyes) FST Type III skin sometimes has a mild burn, tans uniformly (cream white; yellowish; any hair color or brown eyes) FST Type IV skin burns minimally, always tans well (light brown; olive; dark brown to black hair) FST Type V skin very rarely burns, tans very easily (brown) FST Type VI skin never burns, always tans (deeply pigmented dark brown to darkest brown, black in complexion)</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>FST I</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>FST II</title>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                  </measurement_list>
                </category>
                <category>
                  <title>FST III</title>
                  <measurement_list>
                    <measurement group_id="B1" value="83"/>
                  </measurement_list>
                </category>
                <category>
                  <title>FST IV</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>FST V</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>FST VI</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (BMI)</title>
          <description>BMI is the body mass divided by the square of the body height, and is universally expressed in units of kg/m^2</description>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.27" spread="5.374"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Primary Efficacy Variable is Change From Baseline to Visit 6/Week 24 in Wrinkle Severity Rating Scale (WSRS) Score</title>
        <description>Primary efficacy variable is change from Baseline to Visit 6/Week 24 in Wrinkle Severity Rating Scale (WSRS) - Treatment success is defined as at least a 1-grade improvement in WSRS from baseline to Week 24&#xD;
WSRS Score categories:&#xD;
Absent - No visible fold; continuous skin line.&#xD;
Mild - Shallow but visible fold with a slight indentation; minor facial feature; implant is expected to produce a slight improvement in appearance.&#xD;
Moderate - Moderately deep folds; clear facial feature visible at normal appearance but not when stretched; excellent correction is expected from injectable implant.&#xD;
Severe - Very long and deep folds; prominent facial feature; less than 2 mm visible when stretched; significant improvement is expected from injectable implant.&#xD;
Extreme - Extremely deep and long folds, detrimental to facial appearance; 2 to 4 mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone.</description>
        <time_frame>Visit 6/Week 24</time_frame>
        <population>Analysis of effectiveness based on Per Protocol analysis which includes 125 evaluable patients at 24 weeks.</population>
        <group_list>
          <group group_id="O1">
            <title>Revanesse Ultra</title>
            <description>Revanesse Ultra in the NLF on one side of the face&#xD;
Revanesse Ultra: NLF correction</description>
          </group>
          <group group_id="O2">
            <title>Restylane</title>
            <description>Restylane injection in the NLF on the other side of the face to optimal correction&#xD;
Restylane: NLF Correction</description>
          </group>
        </group_list>
        <measure>
          <title>Primary Efficacy Variable is Change From Baseline to Visit 6/Week 24 in Wrinkle Severity Rating Scale (WSRS) Score</title>
          <description>Primary efficacy variable is change from Baseline to Visit 6/Week 24 in Wrinkle Severity Rating Scale (WSRS) - Treatment success is defined as at least a 1-grade improvement in WSRS from baseline to Week 24&#xD;
WSRS Score categories:&#xD;
Absent - No visible fold; continuous skin line.&#xD;
Mild - Shallow but visible fold with a slight indentation; minor facial feature; implant is expected to produce a slight improvement in appearance.&#xD;
Moderate - Moderately deep folds; clear facial feature visible at normal appearance but not when stretched; excellent correction is expected from injectable implant.&#xD;
Severe - Very long and deep folds; prominent facial feature; less than 2 mm visible when stretched; significant improvement is expected from injectable implant.&#xD;
Extreme - Extremely deep and long folds, detrimental to facial appearance; 2 to 4 mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone.</description>
          <population>Analysis of effectiveness based on Per Protocol analysis which includes 125 evaluable patients at 24 weeks.</population>
          <units>scores on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <units_analyzed>Nasolabial Folds</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="125"/>
                <count group_id="O2" value="125"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Nasolabial Folds</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="125"/>
                <count group_id="O2" value="125"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.02" lower_limit="0.902" upper_limit="1.146"/>
                    <measurement group_id="O2" value="0.91" lower_limit="0.777" upper_limit="1.047"/>
                  </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>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>If the upper bound of this 95% CI was less than the prespecified non-inferiority limit of 0.50, the Test product would be claimed to be non-inferior to the Comparator product.</non_inferiority_desc>
            <p_value>0.0130</p_value>
            <p_value_desc>Wilcoxon matched-pairs signed rank test</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints Are the Responder Rate, Percentage of *Nasolabial Folds* With Treatment Success</title>
        <description>Treatment success (defined as at least a 1-grade improvement in WSRS from baseline to Week 24):&#xD;
The WSRS Score is a 5-point scale. The WSRS score was assessed for each NLF at every study visit through Visit 6/Week 24 by a blinded evaluator (blinded to the treatment assignment of each NLF).</description>
        <time_frame>Visit 6/Week 24</time_frame>
        <population>Per-Protocol (PP) Population</population>
        <group_list>
          <group group_id="O1">
            <title>Revanesse Ultra</title>
            <description>Revanesse Ultra in the NLF on one side of the face&#xD;
Revanesse Ultra: NLF correction</description>
          </group>
          <group group_id="O2">
            <title>Restylane</title>
            <description>Restylane injection in the NLF on the other side of the face to optimal correction&#xD;
Restylane: NLF Correction</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints Are the Responder Rate, Percentage of *Nasolabial Folds* With Treatment Success</title>
          <description>Treatment success (defined as at least a 1-grade improvement in WSRS from baseline to Week 24):&#xD;
The WSRS Score is a 5-point scale. The WSRS score was assessed for each NLF at every study visit through Visit 6/Week 24 by a blinded evaluator (blinded to the treatment assignment of each NLF).</description>
          <population>Per-Protocol (PP) Population</population>
          <units>Nasolabial Folds</units>
          <param>Count of Units</param>
          <units_analyzed>Nasolabial Folds</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="125"/>
                <count group_id="O2" value="125"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Nasolabial Folds</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="125"/>
                <count group_id="O2" value="125"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98"/>
                    <measurement group_id="O2" value="91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Other Efficacy Variables Include Change in WSRS Score</title>
        <description>Treatment success is (defined as at least a 1-grade improvement in WSRS from baseline to Week 24)</description>
        <time_frame>Visit 2/Week 1, Visit 3/Week 2, Visit 4/Week 4, and Visit 5/Week 12</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Other Efficacy Variables Include Change in Patient Global Aesthetic Improvement (pGAI) Score</title>
        <description>Treatment success is (defined as at least a 1-grade improvement in WSRS from baseline to Week 24)</description>
        <time_frame>Visit 2/Week 1, Visit 3/Week 2, Visit 4/Week 4, and Visit 5/Week 12</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Other Efficacy Variables Include Change in Investigator Global Aesthetic Improvement (iGAI) Score</title>
        <description>Treatment success is (defined as at least a 1-grade improvement in WSRS from baseline to Week 24)</description>
        <time_frame>Visit 2/Week 1, Visit 3/Week 2, Visit 4/Week 4, and Visit 5/Week 12</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>24 weeks</time_frame>
      <desc>Treatment safety was evaluated by frequency and percent of subjects and investigators reporting treatment-emergent adverse events (TEAEs) tabulated by treatment group, location, frequency, severity and duration after each treatment (initial treatment, touch up) and throughout the study. TEAEs were assessed by a subject diary after each injection, touch up and follow up visit, and were reported by the Evaluating Investigator at each of the follow-up visits</desc>
      <group_list>
        <group group_id="E1">
          <title>Revanesse Ultra</title>
          <description>Revanesse Ultra in the NLF on one side of the face&#xD;
Revanesse Ultra: NLF correction</description>
        </group>
        <group group_id="E2">
          <title>Restylane</title>
          <description>Restylane injection in the NLF on the other side of the face to optimal correction&#xD;
Restylane: NLF Correction</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 15.1</default_vocab>
        <default_assessment>Non-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="0" subjects_at_risk="163"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="163"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="163"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="163"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Treatment emergent Injection site vascular complication</sub_title>
                <description>Device related serious adverse event of a possible vascular event</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="163"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="163"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 15.1</default_vocab>
        <default_assessment>Non-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="114" subjects_at_risk="163"/>
                <counts group_id="E2" subjects_affected="137" subjects_at_risk="163"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>INJECTION SITE HAEMATOMA</sub_title>
                <description>bruising at the injection site</description>
                <counts group_id="E1" events="106" subjects_affected="82" subjects_at_risk="163"/>
                <counts group_id="E2" events="95" subjects_affected="77" subjects_at_risk="163"/>
              </event>
              <event>
                <sub_title>INJECTION SITE SWELLING</sub_title>
                <description>swelling at the injection site</description>
                <counts group_id="E1" events="102" subjects_affected="77" subjects_at_risk="163"/>
                <counts group_id="E2" events="163" subjects_affected="116" subjects_at_risk="163"/>
              </event>
              <event>
                <sub_title>INJECTION SITE PAIN</sub_title>
                <description>pain at the injection site</description>
                <counts group_id="E1" events="103" subjects_affected="62" subjects_at_risk="163"/>
                <counts group_id="E2" events="192" subjects_affected="108" subjects_at_risk="163"/>
              </event>
              <event>
                <sub_title>INJECTION SITE ERYTHEMA</sub_title>
                <description>redness at the injection site</description>
                <counts group_id="E1" events="44" subjects_affected="35" subjects_at_risk="163"/>
                <counts group_id="E2" events="65" subjects_affected="52" subjects_at_risk="163"/>
              </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 are restrictions within the site contracts that the sites cannot publish any results and also have confidentiality agreements in place separately that restrict any publications by sites regarding results, findings, etc.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Ario Khoshbin, President</name_or_title>
      <organization>Prollenium Medical Technologies, Inc.</organization>
      <phone>866-353-3015</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/NCT02987205
org study id: SYM2014-02
nct id: NCT02987205
lead sponsor: 
has dmc: Yes
is fda regulated device: Yes
A randomized, multicenter, double blind, split-face study in subjects seeking NLF correction.
      Subjects were treated with Revanesse Ultra in the NLF on one side of the face and Restylane
      in the NLF on the other side of the face. The side of the face for each product was randomly
      assigned. The investigator performing the evaluations and the subject were blinded to the
      treatment; injections of the study product were performed by an unblinded injecting
      investigator.
The study was a randomized, double-blind prospective, comparative study of the efficacy and
      safety of Revanesse Ultra versus the approved product Restylane in the cutaneous correction
      of NLFs. Randomization followed a 1:1 within-subject control model of augmentation correction
      of NLFs. Given that the implants have been shown to not migrate, the within-subject model was
      ideal and had already been shown in previous studies to detect differences. Subjects with
      signs of NLFs who met the entry criteria were enrolled. All subjects were followed for
      efficacy and safety for 6 months. Subjects could have open-label retreatment as needed with
      Revanesse Ultra at 6 months if their baseline WSRS scores had returned to baseline, or as
      needed to achieve optimal correction if their baseline WSRS scores had not returned to
      baseline and were followed for a total of 12 months. The study design was appropriate for the
      indication studied.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Primary Efficacy Variable is Change From Baseline to Visit 6/Week 24 in Wrinkle Severity Rating Scale (WSRS) Score
time frame: Visit 6/Week 24
description: Primary efficacy variable is change from Baseline to Visit 6/Week 24 in Wrinkle Severity Rating Scale (WSRS) - Treatment success is defined as at least a 1-grade improvement in WSRS from baseline to Week 24
WSRS Score categories:
Absent - No visible fold; continuous skin line.
Mild - Shallow but visible fold with a slight indentation; minor facial feature; implant is expected to produce a slight improvement in appearance.
Moderate - Moderately deep folds; clear facial feature visible at normal appearance but not when stretched; excellent correction is expected from injectable implant.
Severe - Very long and deep folds; prominent facial feature; less than 2 mm visible when stretched; significant improvement is expected from injectable implant.
Extreme - Extremely deep and long folds, detrimental to facial appearance; 2 to 4 mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone.
measure: Secondary Efficacy Endpoints Are the Responder Rate, Percentage of *Nasolabial Folds* With Treatment Success
time frame: Visit 6/Week 24
description: Treatment success (defined as at least a 1-grade improvement in WSRS from baseline to Week 24):
The WSRS Score is a 5-point scale. The WSRS score was assessed for each NLF at every study visit through Visit 6/Week 24 by a blinded evaluator (blinded to the treatment assignment of each NLF).
measure: Other Efficacy Variables Include Change in WSRS Score
time frame: Visit 2/Week 1, Visit 3/Week 2, Visit 4/Week 4, and Visit 5/Week 12
description: Treatment success is (defined as at least a 1-grade improvement in WSRS from baseline to Week 24)
measure: Other Efficacy Variables Include Change in Patient Global Aesthetic Improvement (pGAI) Score
time frame: Visit 2/Week 1, Visit 3/Week 2, Visit 4/Week 4, and Visit 5/Week 12
description: Treatment success is (defined as at least a 1-grade improvement in WSRS from baseline to Week 24)
measure: Other Efficacy Variables Include Change in Investigator Global Aesthetic Improvement (iGAI) Score
time frame: Visit 2/Week 1, Visit 3/Week 2, Visit 4/Week 4, and Visit 5/Week 12
description: Treatment success is (defined as at least a 1-grade improvement in WSRS from baseline to Week 24)
arm group label: Revanesse Ultra
arm group type: Experimental
description: Revanesse Ultra in the NLF on one side of the face
arm group label: Restylane
arm group type: Active Comparator
description: Restylane injection in the NLF on the other side of the face to optimal correction
intervention type: Device
intervention name: Revanesse Ultra
description: NLF correction
arm group label: Revanesse Ultra
intervention type: Device
intervention name: Restylane
description: NLF Correction
arm group label: Restylane
criteria: 
gender: All
minimum age: 22 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Michael H Gold, MD
role: Principal Investigator
affiliation: Tennessee Clinical Research Center
responsible party type: Sponsor
sharing ipd: Undecided
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 