<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/NCT03777917</url>
  </required_header>
  <id_info>
    <org_study_id>M930121001</org_study_id>
    <nct_id>NCT03777917</nct_id>
  </id_info>
  <brief_title>A Pilot Study to Assess the Effectiveness and Safety of Belotero Balance® Injection for Volume Augmentation of the Infraorbital Hollow</brief_title>
  <official_title>Pilot Study to Assess the Effectiveness and Safety of Belotero Balance® Injection for Volume Augmentation of the Infraorbital Hollow</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merz North America, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merz North America, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The pilot study aims to define safety, effectiveness, and patient-reported outcomes for&#xD;
      Belotero Balance® use in the infraorbital hollows.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 27, 2018</start_date>
  <completion_date type="Actual">March 11, 2020</completion_date>
  <primary_completion_date type="Actual">June 18, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Responder Rate Compared to the Untreated Control Group According to the Merz Infraorbital Hollow Assessment Scale (MIHAS).</measure>
    <time_frame>Baseline up to Month 2</time_frame>
    <description>MIHAS was a 5 point scale ranging as: Grade 0 (none to minimal), Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (extreme). Responder rate was defined as percentage of participants with treatment response who achieved greater than or equal to (&gt;=) 1 grade improvement on both IOHs on the MIHAS.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Rasch-Transformed Score for the Face-Q Satisfaction With Eyes</measure>
    <time_frame>Baseline and Month 2</time_frame>
    <description>The FACE-Q is a set of standardized patient-reported outcome scales for participants undergoing facial cosmetic procedures. The participants answered 7 questions of the FACE-Q satisfaction with eyes scale using a 4 point scale where: 1 (very dissatisfied), 2 (somewhat dissatisfied), 3 (somewhat satisfied), 4 (very satisfied). The sum scores of the FACE-Q satisfaction with eyes questionnaire and the Rasch-transformed scores ranging from 0 to 100 were summarized by treatment arm. Higher scores reflected a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global Aesthetic Improvement Scale (GAIS) Scores</measure>
    <time_frame>Baseline up to Month 2</time_frame>
    <description>7 point rating scale ranging from: +3 (very much improved), +2 (much improved), +1 (improved), 0 (no change), -1 (worse), -2 (much worse), -3 (very much worse).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GAIS Scores as Assessed by Participants</measure>
    <time_frame>Baseline up to Month 2</time_frame>
    <description>Participants evaluated their IOHs on 7 point rating scale ranging from: +3 (very much improved), +2 (much improved), +1 (improved), 0 (no change), -1 (worse), -2 (much worse), -3 (very much worse).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Responder Rate in the Treatment Group and the Untreated Control Group According to MIHAS as Assessed by Independent Panel Reviewers</measure>
    <time_frame>Baseline up to Month 2</time_frame>
    <description>MIHAS was a 5 point scale ranging as: 0 (none to minimal), 1 (mild), 2 (moderate), 3 (severe), 4 (extreme). Responder rate was defined as percentage of participants with treatment response who achieved &gt;=1 improvement on both IOHs compared to baseline. A participant was considered a responder if a treatment response of at least a 1-point change on both IOHs was determined by independent panel reviewers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Reporting One or More Device and/or Injection Related Treatment-emergent Adverse Events (TEAEs) and Device and/or Injection Related Serious TEAEs</measure>
    <time_frame>Treatment Group: Baseline up to Month 13; Untreated Control Group: Baseline up to Month 2</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">66</enrollment>
  <condition>Correction of Volume Loss in the Infraorbital Hollow Area</condition>
  <arm_group>
    <arm_group_label>Belotero Balance®</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>No treatment</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Belotero Balance®</intervention_name>
    <description>Belotero® Balance for infraorbital hollows. Mode of application: subdermal injection.</description>
    <arm_group_label>Belotero Balance®</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Has right and left infraorbital hollow (IOH) volume deficit with a rating of 2 or 3&#xD;
             (moderate or severe) on the MIHAS.&#xD;
&#xD;
          -  Has the same MIHAS score on both IOHs (i.e., IOHs are symmetrical).&#xD;
&#xD;
          -  Is at least 22 years of age.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Ever been treated with fat injections or permanent and/or semi-permanent dermal&#xD;
             fillers in the midfacial region.&#xD;
&#xD;
          -  Received lower eyelid and/or malar region treatments with any absorbable or temporary&#xD;
             fillers such as porcine-based collagen fillers, hyaluronic acid (HA) products,&#xD;
             RADIESSE®, poly L-lactic acid (PLLA) or received mesotherapy treatment to the area&#xD;
             within the past 24 months or plans to receive such treatments during participation in&#xD;
             the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>22 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Merz Medical Expert</last_name>
    <role>Study Director</role>
    <affiliation>Merz North America, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Center for Sight, Merz Investigational Site #0010414</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Private Practice, Merz Investigational Site #0010413</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Laser and Facial Surgery, Merz Investigational Site #0010353</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>December 4, 2018</study_first_submitted>
  <study_first_submitted_qc>December 14, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 17, 2018</study_first_posted>
  <results_first_submitted>June 14, 2022</results_first_submitted>
  <results_first_submitted_qc>September 1, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">September 2, 2022</results_first_posted>
  <disposition_first_submitted>June 15, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>September 1, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">September 2, 2022</disposition_first_posted>
  <last_update_submitted>September 1, 2022</last_update_submitted>
  <last_update_submitted_qc>September 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyaluronic Acid</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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>March 15, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/17/NCT03777917/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 15, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/17/NCT03777917/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>3 investigational sites in the United States.</recruitment_details>
      <pre_assignment_details>A total of 66 participants were randomized.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Treatment With Belotero Balance®</title>
          <description>IOH injected with Belotero Balance®.</description>
        </group>
        <group group_id="P2">
          <title>Untreated Control Group</title>
          <description>No treatment.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="43"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Safety Population</title>
              <participants_list>
                <participants group_id="P1" count="43"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety population (SP) consisted of all randomized participants who received at least one study treatment in the active treatment group or who were randomized into the control arm.</population>
      <group_list>
        <group group_id="B1">
          <title>Treatment With Belotero Balance®</title>
          <description>Belotero Balance®, subcutaneous injection for IOHs.</description>
        </group>
        <group group_id="B2">
          <title>Untreated Control Group</title>
          <description>No treatment.</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="43"/>
            <count group_id="B2" value="22"/>
            <count group_id="B3" value="65"/>
          </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="45.9" spread="12.6"/>
                    <measurement group_id="B2" value="47.3" spread="11.6"/>
                    <measurement group_id="B3" value="46.4" spread="12.2"/>
                  </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="37"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="55"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="10"/>
                  </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="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="58"/>
                  </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="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="55"/>
                  </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_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Responder Rate Compared to the Untreated Control Group According to the Merz Infraorbital Hollow Assessment Scale (MIHAS).</title>
        <description>MIHAS was a 5 point scale ranging as: Grade 0 (none to minimal), Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (extreme). Responder rate was defined as percentage of participants with treatment response who achieved greater than or equal to (&gt;=) 1 grade improvement on both IOHs on the MIHAS.</description>
        <time_frame>Baseline up to Month 2</time_frame>
        <population>The intent-to-treat (ITT) population consisted of all randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment With Belotero Balance®</title>
            <description>Belotero Balance®, subcutaneous injection for IOHs.</description>
          </group>
          <group group_id="O2">
            <title>Untreated Control Group</title>
            <description>No treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Responder Rate Compared to the Untreated Control Group According to the Merz Infraorbital Hollow Assessment Scale (MIHAS).</title>
          <description>MIHAS was a 5 point scale ranging as: Grade 0 (none to minimal), Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (extreme). Responder rate was defined as percentage of participants with treatment response who achieved greater than or equal to (&gt;=) 1 grade improvement on both IOHs on the MIHAS.</description>
          <population>The intent-to-treat (ITT) population consisted of all randomized participants.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81.6"/>
                    <measurement group_id="O2" value="9.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Fisher Exact</method>
            <method_desc>The Fisher's exact test was used to test for the superiority of treatment (Belotero Balance®) over control.</method_desc>
            <param_type>Difference in Response Rates</param_type>
            <param_value>72.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>47.5</ci_lower_limit>
            <ci_upper_limit>83.5</ci_upper_limit>
            <estimate_desc>Two-sided Newcombe confidence interval (CI) for the difference in response rates.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Rasch-Transformed Score for the Face-Q Satisfaction With Eyes</title>
        <description>The FACE-Q is a set of standardized patient-reported outcome scales for participants undergoing facial cosmetic procedures. The participants answered 7 questions of the FACE-Q satisfaction with eyes scale using a 4 point scale where: 1 (very dissatisfied), 2 (somewhat dissatisfied), 3 (somewhat satisfied), 4 (very satisfied). The sum scores of the FACE-Q satisfaction with eyes questionnaire and the Rasch-transformed scores ranging from 0 to 100 were summarized by treatment arm. Higher scores reflected a better outcome.</description>
        <time_frame>Baseline and Month 2</time_frame>
        <population>The ITT population consisted of all randomized participants. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment With Belotero Balance®</title>
            <description>Belotero Balance®, subcutaneous injection for IOHs.</description>
          </group>
          <group group_id="O2">
            <title>Untreated Control Group</title>
            <description>No treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Rasch-Transformed Score for the Face-Q Satisfaction With Eyes</title>
          <description>The FACE-Q is a set of standardized patient-reported outcome scales for participants undergoing facial cosmetic procedures. The participants answered 7 questions of the FACE-Q satisfaction with eyes scale using a 4 point scale where: 1 (very dissatisfied), 2 (somewhat dissatisfied), 3 (somewhat satisfied), 4 (very satisfied). The sum scores of the FACE-Q satisfaction with eyes questionnaire and the Rasch-transformed scores ranging from 0 to 100 were summarized by treatment arm. Higher scores reflected a better outcome.</description>
          <population>The ITT population consisted of all randomized participants. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.8" lower_limit="21.2" upper_limit="36.5"/>
                    <measurement group_id="O2" value="2.1" lower_limit="-3.9" upper_limit="8.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Global Aesthetic Improvement Scale (GAIS) Scores</title>
        <description>7 point rating scale ranging from: +3 (very much improved), +2 (much improved), +1 (improved), 0 (no change), -1 (worse), -2 (much worse), -3 (very much worse).</description>
        <time_frame>Baseline up to Month 2</time_frame>
        <population>The ITT population consisted of all randomized participants. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this OM was evaluated only for participants treated with Belotero Balance®.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment With Belotero Balance®</title>
            <description>Belotero Balance®, subcutaneous injection for IOHs.</description>
          </group>
        </group_list>
        <measure>
          <title>Global Aesthetic Improvement Scale (GAIS) Scores</title>
          <description>7 point rating scale ranging from: +3 (very much improved), +2 (much improved), +1 (improved), 0 (no change), -1 (worse), -2 (much worse), -3 (very much worse).</description>
          <population>The ITT population consisted of all randomized participants. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this OM was evaluated only for participants treated with Belotero Balance®.</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="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Very Much Improved (+3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Much Improved (+2)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Improved (+1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No Change (0)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Worse (-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Much Worse (-2)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Very Much Worse (-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>GAIS Scores as Assessed by Participants</title>
        <description>Participants evaluated their IOHs on 7 point rating scale ranging from: +3 (very much improved), +2 (much improved), +1 (improved), 0 (no change), -1 (worse), -2 (much worse), -3 (very much worse).</description>
        <time_frame>Baseline up to Month 2</time_frame>
        <population>The ITT population consisted of all randomized participants. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this OM was evaluated only for participants treated with Belotero Balance®.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment With Belotero Balance®</title>
            <description>Belotero Balance®, subcutaneous injection for IOHs.</description>
          </group>
        </group_list>
        <measure>
          <title>GAIS Scores as Assessed by Participants</title>
          <description>Participants evaluated their IOHs on 7 point rating scale ranging from: +3 (very much improved), +2 (much improved), +1 (improved), 0 (no change), -1 (worse), -2 (much worse), -3 (very much worse).</description>
          <population>The ITT population consisted of all randomized participants. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this OM was evaluated only for participants treated with Belotero Balance®.</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="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Very Much Improved (+3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Much Improved (+2)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Improved (+1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No Change (0)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Worse (-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Much Worse (-2)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Very Much Worse (-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Responder Rate in the Treatment Group and the Untreated Control Group According to MIHAS as Assessed by Independent Panel Reviewers</title>
        <description>MIHAS was a 5 point scale ranging as: 0 (none to minimal), 1 (mild), 2 (moderate), 3 (severe), 4 (extreme). Responder rate was defined as percentage of participants with treatment response who achieved &gt;=1 improvement on both IOHs compared to baseline. A participant was considered a responder if a treatment response of at least a 1-point change on both IOHs was determined by independent panel reviewers.</description>
        <time_frame>Baseline up to Month 2</time_frame>
        <population>The ITT population consisted of all randomized participants. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment With Belotero Balance®</title>
            <description>Belotero Balance®, subcutaneous injection for IOHs.</description>
          </group>
          <group group_id="O2">
            <title>Untreated Control Group</title>
            <description>No treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Responder Rate in the Treatment Group and the Untreated Control Group According to MIHAS as Assessed by Independent Panel Reviewers</title>
          <description>MIHAS was a 5 point scale ranging as: 0 (none to minimal), 1 (mild), 2 (moderate), 3 (severe), 4 (extreme). Responder rate was defined as percentage of participants with treatment response who achieved &gt;=1 improvement on both IOHs compared to baseline. A participant was considered a responder if a treatment response of at least a 1-point change on both IOHs was determined by independent panel reviewers.</description>
          <population>The ITT population consisted of all randomized participants. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.8"/>
                    <measurement group_id="O2" value="9.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Reporting One or More Device and/or Injection Related Treatment-emergent Adverse Events (TEAEs) and Device and/or Injection Related Serious TEAEs</title>
        <time_frame>Treatment Group: Baseline up to Month 13; Untreated Control Group: Baseline up to Month 2</time_frame>
        <population>The SP consisted of all randomized participants who received at least one study treatment in the active treatment group or who were randomized into the control arm.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment With Belotero Balance®</title>
            <description>Belotero Balance®, subcutaneous injection at baseline for IOHs.</description>
          </group>
          <group group_id="O2">
            <title>Untreated Control Group</title>
            <description>No treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Reporting One or More Device and/or Injection Related Treatment-emergent Adverse Events (TEAEs) and Device and/or Injection Related Serious TEAEs</title>
          <population>The SP consisted of all randomized participants who received at least one study treatment in the active treatment group or who were randomized into the control arm.</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="43"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Treatment Group : Baseline up to Month 13; Untreated Control Group: Baseline up to Month 2</time_frame>
      <desc>The investigator reported AEs systematically at each visit.</desc>
      <group_list>
        <group group_id="E1">
          <title>Treatment With Belotero Balance®</title>
          <description>Belotero Balance®, subcutaneous injection for IOHs.</description>
        </group>
        <group group_id="E2">
          <title>Untreated Control Group</title>
          <description>No treatment.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 22.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Retinal detachment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Vitreous detachment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2.5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
              </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>Publication of study information usually requires agreement with the sponsor. In case of justified doubts by the sponsor, the INVESTIGATOR will consider these doubts in the publication as long as the scientific neutrality is not affected.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Public Disclosure Manager</name_or_title>
      <organization>Merz Pharmaceuticals GmbH</organization>
      <phone>+49 69 1503 1</phone>
      <email>Aesthetic.Trials@merz.com</email>
    </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/NCT03777917
org study id: M930121001
nct id: NCT03777917
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
The pilot study aims to define safety, effectiveness, and patient-reported outcomes for
      Belotero Balance® use in the infraorbital hollows.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Responder Rate Compared to the Untreated Control Group According to the Merz Infraorbital Hollow Assessment Scale (MIHAS).
time frame: Baseline up to Month 2
description: MIHAS was a 5 point scale ranging as: Grade 0 (none to minimal), Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (extreme). Responder rate was defined as percentage of participants with treatment response who achieved greater than or equal to (>=) 1 grade improvement on both IOHs on the MIHAS.
measure: Change From Baseline in Rasch-Transformed Score for the Face-Q Satisfaction With Eyes
time frame: Baseline and Month 2
description: The FACE-Q is a set of standardized patient-reported outcome scales for participants undergoing facial cosmetic procedures. The participants answered 7 questions of the FACE-Q satisfaction with eyes scale using a 4 point scale where: 1 (very dissatisfied), 2 (somewhat dissatisfied), 3 (somewhat satisfied), 4 (very satisfied). The sum scores of the FACE-Q satisfaction with eyes questionnaire and the Rasch-transformed scores ranging from 0 to 100 were summarized by treatment arm. Higher scores reflected a better outcome.
measure: Global Aesthetic Improvement Scale (GAIS) Scores
time frame: Baseline up to Month 2
description: 7 point rating scale ranging from: +3 (very much improved), +2 (much improved), +1 (improved), 0 (no change), -1 (worse), -2 (much worse), -3 (very much worse).
measure: GAIS Scores as Assessed by Participants
time frame: Baseline up to Month 2
description: Participants evaluated their IOHs on 7 point rating scale ranging from: +3 (very much improved), +2 (much improved), +1 (improved), 0 (no change), -1 (worse), -2 (much worse), -3 (very much worse).
measure: Responder Rate in the Treatment Group and the Untreated Control Group According to MIHAS as Assessed by Independent Panel Reviewers
time frame: Baseline up to Month 2
description: MIHAS was a 5 point scale ranging as: 0 (none to minimal), 1 (mild), 2 (moderate), 3 (severe), 4 (extreme). Responder rate was defined as percentage of participants with treatment response who achieved >=1 improvement on both IOHs compared to baseline. A participant was considered a responder if a treatment response of at least a 1-point change on both IOHs was determined by independent panel reviewers.
measure: Number of Participants Reporting One or More Device and/or Injection Related Treatment-emergent Adverse Events (TEAEs) and Device and/or Injection Related Serious TEAEs
time frame: Treatment Group: Baseline up to Month 13; Untreated Control Group: Baseline up to Month 2
arm group label: Belotero Balance®
arm group type: Experimental
arm group label: No treatment
arm group type: No Intervention
intervention type: Device
intervention name: Belotero Balance®
description: Belotero® Balance for infraorbital hollows. Mode of application: subdermal injection.
arm group label: Belotero Balance®
criteria: 
gender: All
minimum age: 22 Years
maximum age: N/A
healthy volunteers: No
last name: Merz Medical Expert
role: Study Director
affiliation: Merz North America, Inc.
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hyaluronic Acid
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 