<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/NCT02984878</url>
  </required_header>
  <id_info>
    <org_study_id>SYM2014-02 Retreatment</org_study_id>
    <nct_id>NCT02984878</nct_id>
  </id_info>
  <brief_title>Multicenter Study to Evaluate the Safety and Efficacy of Revanesse® Ultra Retreatment</brief_title>
  <acronym>Retreatment</acronym>
  <official_title>A Multicenter, Double-Blind, Randomized, Split-Face Study to Evaluate the Safety and Efficacy of Revanesse® Ultra (Retreatment)</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>
      To compare improvement with retreatment for all subjects undergoing correction of nasolabial&#xD;
      folds (NLFs) in the initial SYM2014-02 study, who were retreated with Revanesse Ultra at&#xD;
      Visit 6/Week 24 and to determine the safety of repeat injections of Revanesse Ultra. The&#xD;
      retreatment phase was optional.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The subjects completing the initial phase of the SYM2014-02 study (NCT02987205) who had&#xD;
      returned to baseline Wrinkle Severity Rating Scale (WSRS) score or as needed for optimal&#xD;
      correction if WSRS scores had not returned to baseline, were offered the option for&#xD;
      retreatment with Revanesse Ultra&#xD;
&#xD;
      Visit 6/Week 24 (± 7 days) optional open-label retreatment with Revanesse Ultra for subjects&#xD;
      who had returned to baseline Wrinkle Severity Rating Scale (WSRS) score or as needed for&#xD;
      optimal correction if WSRS scores had not returned to baseline; End of Study for subjects not&#xD;
      being retreated&#xD;
&#xD;
      Visit 7/Week 28 (± 7 days) follow-up for retreated subjects&#xD;
&#xD;
      Visit 8/Week 52 (± 7 days) End of Study for retreated subjects&#xD;
&#xD;
      A telephone contact was performed at Week 40 (± 7 days) for retreated subjects to assess&#xD;
      adverse events (AEs) and concomitant medications.&#xD;
&#xD;
      This report presents the results for all subjects who received optional open-label&#xD;
      retreatment with Revanesse Ultra at Visit 6/Week 24.&#xD;
&#xD;
      This study was performed in compliance with Good Clinical Practice (GCP), including the&#xD;
      archiving of essential documents.&#xD;
&#xD;
      Number of Subjects (Planned and Analyzed): Seventy-one subjects received retreatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2015</start_date>
  <completion_date type="Actual">September 2016</completion_date>
  <primary_completion_date type="Actual">September 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in the Wrinkle Severity Rating Scale (WSRS) With Subjects From Both the Retreatment and the Optimal Correction Groups - WSRS Scores at Visit 8/Week 52</measure>
    <time_frame>Visit 8/Week 52</time_frame>
    <description>Change in the Wrinkle Severity Rating Scale (WSRS) With Subjects From Both the Retreatment and the Optimal Correction Groups Achieving Similar WSRS Scores at Visit 8/Week 52 - WSRS Score categories: 1. Absent - No visible fold; continuous skin line. 2. Mild - Shallow but visible fold with a slight indentation; minor facial feature; implant is expected to produce a slight improvement in appearance. 3. Moderate - Moderately deep folds; clear facial feature visible at normal appearance but not when stretched; excellent correction is expected from injectable implant. 4. Severe - Very long and deep folds; prominent facial feature; less than 2 mm visible when stretched; significant improvement is expected from injectable implant. 5. 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. An increase in the WSRS score indicates a worsening of severity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity</measure>
    <time_frame>Visit 6/Week 24, Visit 7/Week 28, Visit 8/Week 52</time_frame>
    <description>Assess safety concerns with retreatment of Revanesse Ultra for men or women at least 22 years of age with NLFs with a moderate or severe WSRS score at baseline who had previously received 1 or 2 treatments with Restylane or Revanesse Ultra, Adverse Events (AEs), which were defined, recorded, reported, and evaluated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Global Aesthetic Improvement (pGAI) Score</measure>
    <time_frame>Visit 8/Week 52</time_frame>
    <description>Subjects were evaluated on the Patient Global Aesthetic Improvement (pGAI) Patient Global Aesthetic Improvement (pGAI) Score: 1 = Worse, 2 = No change, 3 = Improved, 4 = Much improved, 5 = Very much improved</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">71</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 open label retreatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Revanesse Ultra</intervention_name>
    <description>Nasolabial Fold correction</description>
    <arm_group_label>Revanesse Ultra</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subjects from the SYM2014-02 initial study who were:&#xD;
&#xD;
          -  Men or women at least 22 years of age with two fully visible bilateral nasolabial&#xD;
             folds each with a WSRS score of 3 or 4 (moderate or severe) that may have been&#xD;
             corrected with an injectable dermal filler.&#xD;
&#xD;
          -  Subjects were eligible for retreatment when WSRS scores had returned to baseline for&#xD;
             either or both NLFs (retreatment group).&#xD;
&#xD;
          -  If scores had not returned to baseline, subjects were also eligible to be injected for&#xD;
             either one or both NLFs as needed to achieve optimal correction (optimal correction&#xD;
             group).&#xD;
&#xD;
        Exclusion Criteria:&#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>October 2017</verification_date>
  <study_first_submitted>December 5, 2016</study_first_submitted>
  <study_first_submitted_qc>December 5, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 7, 2016</study_first_posted>
  <results_first_submitted>August 28, 2017</results_first_submitted>
  <results_first_submitted_qc>December 19, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">December 20, 2017</results_first_posted>
  <last_update_submitted>December 19, 2017</last_update_submitted>
  <last_update_submitted_qc>December 19, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 20, 2017</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>December 12, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/78/NCT02984878/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Revanesse Ultra Retreatment</title>
          <description>Revanesse Ultra: Nasolabial Fold correction - - Subjects could have open-label retreatment as needed with Revanesse Ultra at 6 months if their WSRS scores had returned to baseline</description>
        </group>
        <group group_id="P2">
          <title>Revanesse Ultra Optimal Correction</title>
          <description>The Optimal Correction group scores had not returned to baseline, subjects were eligible to be injected for either one or both NLFs as needed to achieve optimal correction (optimal correction group).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="41"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="41"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Revanesse Ultra open label retreatment / Nasolabial Fold correction - optional open-label retreatment with Revanesse Ultra for subjects who had returned to baseline Wrinkle Severity Rating Scale (WSRS) score or as needed for optimal correction if WSRS scores had not returned to baseline.</population>
      <group_list>
        <group group_id="B1">
          <title>Revanesse Ultra Retreatment</title>
          <description>Revanesse Ultra open label retreatment / Nasolabial Fold correction - optional open-label retreatment with Revanesse Ultra for subjects who had returned to baseline Wrinkle Severity Rating Scale (WSRS) score The subjects completing the initial phase of the SYM2014-02 study (NCT02987205) who had returned to baseline Wrinkle Severity Rating Scale (WSRS) score, were offered the option for retreatment with Revanesse Ultra Safety data was collected to assess treatment emergent adverse events associated with repeat injections. Seventy-one subjects received retreatment - 30 returned to baseline</description>
        </group>
        <group group_id="B2">
          <title>Revanesse Ultra Optimal Correction</title>
          <description>Revanesse Ultra open label retreatment / Nasolabial Fold correction - optional open-label retreatment with Revanesse Ultra for subjects as needed for optimal correction if WSRS scores had not returned to baseline.&#xD;
The subjects completing the initial phase of the SYM2014-02 study (NCT02987205) were treated as needed for optimal correction if WSRS scores had not returned to baseline, and were offered the option for retreatment with Revanesse Ultra Safety data was collected to assess treatment emergent adverse events associated with repeat injections. Seventy-one subjects received retreatment - 41 were included in the optimal correction group</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="30"/>
            <count group_id="B2" value="41"/>
            <count group_id="B3" value="71"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58.3" spread="9.19"/>
                    <measurement group_id="B2" value="54.5" spread="10.44"/>
                    <measurement group_id="B3" value="56.1" spread="10.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <description>participants in each age group</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>22 to &lt;40 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>40 to &lt;64 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>64 to &lt;75 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt; = 75 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </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="29"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="66"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="59"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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_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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</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>Native Hawaiian or Other Pacific Islander</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>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="66"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="41"/>
                    <measurement group_id="B3" value="71"/>
                  </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>
          <class_list>
            <class>
              <title>FST I</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FST II</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FST III</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FST IV</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FST V</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FST VI</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in the Wrinkle Severity Rating Scale (WSRS) With Subjects From Both the Retreatment and the Optimal Correction Groups - WSRS Scores at Visit 8/Week 52</title>
        <description>Change in the Wrinkle Severity Rating Scale (WSRS) With Subjects From Both the Retreatment and the Optimal Correction Groups Achieving Similar WSRS Scores at Visit 8/Week 52 - WSRS Score categories: 1. Absent - No visible fold; continuous skin line. 2. Mild - Shallow but visible fold with a slight indentation; minor facial feature; implant is expected to produce a slight improvement in appearance. 3. Moderate - Moderately deep folds; clear facial feature visible at normal appearance but not when stretched; excellent correction is expected from injectable implant. 4. Severe - Very long and deep folds; prominent facial feature; less than 2 mm visible when stretched; significant improvement is expected from injectable implant. 5. 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. An increase in the WSRS score indicates a worsening of severity.</description>
        <time_frame>Visit 8/Week 52</time_frame>
        <population>Subjects that completed the SYM 2014-02 Main Study were eligible for the SYM 2014-02 Retreatment Study.</population>
        <group_list>
          <group group_id="O1">
            <title>Optimal Correction Group</title>
            <description>Optional Open label Retreatment at Week 24 / SYM2014-02 Retreatment: At SYM 2014-02 Main Study Visit 6/Week 24, a subject could be retreated with Revanesse Ultra. Subjects were eligible for optimal correction when WSRS scores had not returned to baseline. Optimal Correction subjects were injected in either one or both NLFs as needed to achieve optimal correction. These subjects continued to day 196 (Visit 7 / week 28), received a phone contact at day 280 (week 40), and completed at day 364 (Visit 8 / week 52).</description>
          </group>
          <group group_id="O2">
            <title>Retreatment Group</title>
            <description>Revanesse Ultra open label retreatment for Nasolabial Fold correction. Optional Open-label Retreatment at Visit 6/Week 24 of the SYM 2014-02 Main Study, a subject could be retreated when WSRS scores had returned to baseline for either or both NLFs. The retreatment group and the optimal correction group were separated for data analysis. These subjects continued to day 196 (Visit 7 / week 28), received a phone contact at day 280 (week 40), and completed at day 364 (Visit 8 / week 52).</description>
          </group>
        </group_list>
        <measure>
          <title>Change in the Wrinkle Severity Rating Scale (WSRS) With Subjects From Both the Retreatment and the Optimal Correction Groups - WSRS Scores at Visit 8/Week 52</title>
          <description>Change in the Wrinkle Severity Rating Scale (WSRS) With Subjects From Both the Retreatment and the Optimal Correction Groups Achieving Similar WSRS Scores at Visit 8/Week 52 - WSRS Score categories: 1. Absent - No visible fold; continuous skin line. 2. Mild - Shallow but visible fold with a slight indentation; minor facial feature; implant is expected to produce a slight improvement in appearance. 3. Moderate - Moderately deep folds; clear facial feature visible at normal appearance but not when stretched; excellent correction is expected from injectable implant. 4. Severe - Very long and deep folds; prominent facial feature; less than 2 mm visible when stretched; significant improvement is expected from injectable implant. 5. 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. An increase in the WSRS score indicates a worsening of severity.</description>
          <population>Subjects that completed the SYM 2014-02 Main Study were eligible for the SYM 2014-02 Retreatment Study.</population>
          <units>units on WSRS scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Nasolabial Folds</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Nasolabial Folds</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="81"/>
                <count group_id="O2" value="60"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change in Main Study Treatment - Revanesse Ultra</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="0.69"/>
                    <measurement group_id="O2" value="0.6" spread="0.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change in Main Study Treatment - Restylane</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.69"/>
                    <measurement group_id="O2" value="0.8" spread="0.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity</title>
        <description>Assess safety concerns with retreatment of Revanesse Ultra for men or women at least 22 years of age with NLFs with a moderate or severe WSRS score at baseline who had previously received 1 or 2 treatments with Restylane or Revanesse Ultra, Adverse Events (AEs), which were defined, recorded, reported, and evaluated</description>
        <time_frame>Visit 6/Week 24, Visit 7/Week 28, Visit 8/Week 52</time_frame>
        <population>Counts reflect numbers of subjects reporting one or more injection site TEAE that map to the MedDRA (version 15.1) system organ class/preferred term. At each level of summarization (system organ class or preferred term), subjects reporting more than one injection site TEAE are counted only once.</population>
        <group_list>
          <group group_id="O1">
            <title>Revanesse Ultra Retreatment</title>
            <description>Revanesse Ultra: Nasolabial Fold correction - - Subjects could have open-label retreatment as needed with Revanesse Ultra at 6 months if their WSRS scores had returned to baseline</description>
          </group>
          <group group_id="O2">
            <title>Revanesse Ultra Optimal Correction</title>
            <description>The Optimal Correction group scores had not returned to baseline, subjects were eligible to be injected for either one or both NLFs as needed to achieve optimal correction (optimal correction group).</description>
          </group>
        </group_list>
        <measure>
          <title>Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity</title>
          <description>Assess safety concerns with retreatment of Revanesse Ultra for men or women at least 22 years of age with NLFs with a moderate or severe WSRS score at baseline who had previously received 1 or 2 treatments with Restylane or Revanesse Ultra, Adverse Events (AEs), which were defined, recorded, reported, and evaluated</description>
          <population>Counts reflect numbers of subjects reporting one or more injection site TEAE that map to the MedDRA (version 15.1) system organ class/preferred term. At each level of summarization (system organ class or preferred term), subjects reporting more than one injection site TEAE are counted only once.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Eye disorder - ocular hyperaemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gastrointestinal - mouth cyst</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Injection site erythema</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Injection site haematoma</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Injection site mass</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Injection site pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Injection site pruritis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Injection site swelling</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Contusion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Excoriation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient Global Aesthetic Improvement (pGAI) Score</title>
        <description>Subjects were evaluated on the Patient Global Aesthetic Improvement (pGAI) Patient Global Aesthetic Improvement (pGAI) Score: 1 = Worse, 2 = No change, 3 = Improved, 4 = Much improved, 5 = Very much improved</description>
        <time_frame>Visit 8/Week 52</time_frame>
        <population>Subjects were evaluated on the Patient Global Aesthetic Improvement (pGAI)</population>
        <group_list>
          <group group_id="O1">
            <title>Revanesse Ultra Retreatment</title>
            <description>Revanesse Ultra: Nasolabial Fold correction - Subjects could have open-label retreatment as needed with Revanesse Ultra at 6 months if their WSRS scores had returned to baseline</description>
          </group>
          <group group_id="O2">
            <title>Revanesse Ultra Optimal Correction</title>
            <description>The Optimal Correction group scores had not returned to baseline, subjects were eligible to be injected for either one or both NLFs as needed to achieve optimal correction (optimal correction group).</description>
          </group>
        </group_list>
        <measure>
          <title>Patient Global Aesthetic Improvement (pGAI) Score</title>
          <description>Subjects were evaluated on the Patient Global Aesthetic Improvement (pGAI) Patient Global Aesthetic Improvement (pGAI) Score: 1 = Worse, 2 = No change, 3 = Improved, 4 = Much improved, 5 = Very much improved</description>
          <population>Subjects were evaluated on the Patient Global Aesthetic Improvement (pGAI)</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Visit 8 - week 52 pGAI = 1 worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 8 - week 52 pGAI = 2 no change</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 8 - week 52 pGAI = 3 Improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 8 - week 52 pGAI = 4 much improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 8 - week 52 pGAI = 5 Very much improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Event data was collected at Retreatment for 6 months (Visit 8/Week 52 from the Main Study)</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>Retreatment Group</title>
          <description>Revanesse Ultra open label retreatment for Nasolabial Fold correction. Optional Open-label Retreatment at Visit 6/Week 24 of the SYM 2014-02 Main Study, a subject could be retreated when WSRS scores had returned to baseline for either or both NLFs. The retreatment group and the optimal correction group were separated for data analysis. These subjects continued to day 196 (Visit 7 / week 28), received a phone contact at day 280 (week 40), and completed at day 364 (Visit 8 / week 52).</description>
        </group>
        <group group_id="E2">
          <title>Optimal Correction Group</title>
          <description>Optional Open label Retreatment at Week 24 / SYM2014-02 Retreatment: At SYM 2014-02 Main Study Visit 6/Week 24, a subject could be retreated with Revanesse Ultra. Subjects were eligible for optimal correction when WSRS scores had not returned to baseline. Optimal Correction subjects were injected in either one or both NLFs as needed to achieve optimal correction. These subjects continued to day 196 (Visit 7 / week 28), received a phone contact at day 280 (week 40), and completed at day 364 (Visit 8 / week 52).</description>
        </group>
      </group_list>
      <serious_events>
        <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="30"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="41"/>
              </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="16" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>INJECTION SITE ERYTHEMA</sub_title>
                <description>Counts reflect numbers of subjects reporting one or more injection site TEAEs that map to the MedDRA (version 15.1). At each level of summarization (SOC or preferred term) subjects reporting more than one injection site TEAE are only counted once.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>INJECTION SITE HAEMATOMA</sub_title>
                <description>bruising</description>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="30"/>
                <counts group_id="E2" events="19" subjects_affected="19" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>INJECTION SITE PAIN</sub_title>
                <description>pain at the injection site</description>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="30"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>INJECTION SITE SWELLING</sub_title>
                <description>Swelling at the injection site</description>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="30"/>
                <counts group_id="E2" events="14" subjects_affected="14" subjects_at_risk="41"/>
              </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, 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/NCT02984878
org study id: SYM2014-02 Retreatment
nct id: NCT02984878
lead sponsor: 
has dmc: Yes
is fda regulated device: Yes
To compare improvement with retreatment for all subjects undergoing correction of nasolabial
      folds (NLFs) in the initial SYM2014-02 study, who were retreated with Revanesse Ultra at
      Visit 6/Week 24 and to determine the safety of repeat injections of Revanesse Ultra. The
      retreatment phase was optional.
The subjects completing the initial phase of the SYM2014-02 study (NCT02987205) who had
      returned to baseline Wrinkle Severity Rating Scale (WSRS) score or as needed for optimal
      correction if WSRS scores had not returned to baseline, were offered the option for
      retreatment with Revanesse Ultra

      Visit 6/Week 24 (± 7 days) optional open-label retreatment with Revanesse Ultra for subjects
      who had returned to baseline Wrinkle Severity Rating Scale (WSRS) score or as needed for
      optimal correction if WSRS scores had not returned to baseline; End of Study for subjects not
      being retreated

      Visit 7/Week 28 (± 7 days) follow-up for retreated subjects

      Visit 8/Week 52 (± 7 days) End of Study for retreated subjects

      A telephone contact was performed at Week 40 (± 7 days) for retreated subjects to assess
      adverse events (AEs) and concomitant medications.

      This report presents the results for all subjects who received optional open-label
      retreatment with Revanesse Ultra at Visit 6/Week 24.

      This study was performed in compliance with Good Clinical Practice (GCP), including the
      archiving of essential documents.

      Number of Subjects (Planned and Analyzed): Seventy-one subjects received retreatment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in the Wrinkle Severity Rating Scale (WSRS) With Subjects From Both the Retreatment and the Optimal Correction Groups - WSRS Scores at Visit 8/Week 52
time frame: Visit 8/Week 52
description: Change in the Wrinkle Severity Rating Scale (WSRS) With Subjects From Both the Retreatment and the Optimal Correction Groups Achieving Similar WSRS Scores at Visit 8/Week 52 - WSRS Score categories: 1. Absent - No visible fold; continuous skin line. 2. Mild - Shallow but visible fold with a slight indentation; minor facial feature; implant is expected to produce a slight improvement in appearance. 3. Moderate - Moderately deep folds; clear facial feature visible at normal appearance but not when stretched; excellent correction is expected from injectable implant. 4. Severe - Very long and deep folds; prominent facial feature; less than 2 mm visible when stretched; significant improvement is expected from injectable implant. 5. 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. An increase in the WSRS score indicates a worsening of severity.
measure: Retreatment Safety Assessed by the Incidence of Adverse Events (AEs), Which Were Defined, Recorded, Reported, and Evaluated, by Number and Severity
time frame: Visit 6/Week 24, Visit 7/Week 28, Visit 8/Week 52
description: Assess safety concerns with retreatment of Revanesse Ultra for men or women at least 22 years of age with NLFs with a moderate or severe WSRS score at baseline who had previously received 1 or 2 treatments with Restylane or Revanesse Ultra, Adverse Events (AEs), which were defined, recorded, reported, and evaluated
measure: Patient Global Aesthetic Improvement (pGAI) Score
time frame: Visit 8/Week 52
description: Subjects were evaluated on the Patient Global Aesthetic Improvement (pGAI) Patient Global Aesthetic Improvement (pGAI) Score: 1 = Worse, 2 = No change, 3 = Improved, 4 = Much improved, 5 = Very much improved
arm group label: Revanesse Ultra
arm group type: Experimental
description: Revanesse Ultra open label retreatment
intervention type: Device
intervention name: Revanesse Ultra
description: Nasolabial Fold correction
arm group label: Revanesse Ultra
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: 