<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/NCT03289052</url>
  </required_header>
  <id_info>
    <org_study_id>43CH1626</org_study_id>
    <nct_id>NCT03289052</nct_id>
  </id_info>
  <brief_title>Restylane Volyme for Correction of Midface Volume Deficit and/or Midface Contour Deficiency</brief_title>
  <official_title>A Randomized, Multi-center, Evaluator-blinded, No-treatment Controlled Study to Evaluate the Effectiveness and Safety of Restylane Volyme for Correction of Midface Volume Deficit and/or Midface Contour Deficiency</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Galderma R&amp;D</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Galderma R&amp;D</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, evaluator-blinded, no-treatment controlled study in subjects with&#xD;
      Midface Volume Deficit and/or Midface Contour Deficiency.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 1, 2017</start_date>
  <completion_date type="Actual">July 31, 2019</completion_date>
  <primary_completion_date type="Actual">January 31, 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>Percentage of Responders</measure>
    <time_frame>6 month</time_frame>
    <description>Percentage of responders, defined by at least 1 point improvement from baseline on the MMVS on both sides of the face concurrently, as measured by the blinded evaluator at 6 months after last treatment in Treatment Group, and at 6 months after randomization in Control Group.&#xD;
MMVS is a Four-Point scale that assesses the fullness of the midface from Fairly Full (1) to Substantial Loss of Fullness (4) as described below. The blinded evaluator and treating investigator will rate the subject's right and left midface for severity of volume deficiency using the MMVS at all applicable study visits.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">168</enrollment>
  <condition>Midface Volume Deficit</condition>
  <arm_group>
    <arm_group_label>Restylane Volyme</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single injection and optional touch up injection with Restylane Volyme in Midface</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No intervention arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Restylane Volyme</intervention_name>
    <description>Subcutis injection</description>
    <arm_group_label>Restylane Volyme</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed informed consent&#xD;
&#xD;
          2. Men or women aged 18 years of age or older of Chinese origin&#xD;
&#xD;
          3. Subjects willing to abstain from any other facial plastic surgical or cosmetic&#xD;
             procedures below the level of the lower orbital rim for the duration of the study&#xD;
&#xD;
          4. Subjects seeking augmentation therapy for the midface&#xD;
&#xD;
          5. MMVS score of 2, 3 or 4 on each side of the face as assessed by the blinded evaluator&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known/previous allergy or hypersensitivity to any injectable HA gel/local&#xD;
             anaesthetics, e.g.lidocaine or other amide-type anaesthetics.&#xD;
&#xD;
          2. Previous surgery or tattoo in the area to be treated&#xD;
&#xD;
          3. Previous tissue augmentation therapy or contouring with any permanent&#xD;
             (non-biodegradable) or semi-permanent filler, autologous fat, lifting threads or&#xD;
             permanent implant below the level of the lower orbital rim.&#xD;
&#xD;
          4. Previous use of any hyaluronic acid based or collagen based biodegradable facial&#xD;
             tissue augmentation therapy below the level of the lower orbital rim or neurotoxin&#xD;
             within 9 months before treatment.&#xD;
&#xD;
          5. Scars or deformities, active skin disease, inflammation or related conditions, such as&#xD;
             infection, perioral dermatitis, seborrheic eczema, rosacea, acne psoriasis and herpes&#xD;
             zoster near or in the area to be treated.&#xD;
&#xD;
          6. Other condition preventing the subject from entering the study in the Investigator's&#xD;
             opinion.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Q-Med AB</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>September 18, 2017</study_first_submitted>
  <study_first_submitted_qc>September 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 20, 2017</study_first_posted>
  <results_first_submitted>November 4, 2020</results_first_submitted>
  <results_first_submitted_qc>February 19, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">March 15, 2021</results_first_posted>
  <last_update_submitted>April 17, 2023</last_update_submitted>
  <last_update_submitted_qc>April 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hyaluronic acid, midface</keyword>
  <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>December 9, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/52/NCT03289052/Prot_002.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>December 9, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/52/NCT03289052/SAP_003.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Group A</title>
          <description>The first 2 eligible subjects for each Treating Investigator will receive Restylane Volyme treatment as Group A. The injection technique will be evaluated by the Sponsor and performed after the subjects in Group A for each site have received their first treatment. If treatments are found to be correctly performed, no further training is needed, there are no outstanding questions regarding the injection technique and no other corrective actions are identified, the enrolment in Group B can start for that site. A maximum dosage of 2 mL per treatment site (i.e., right and left midface respectively) is recommended at each treatment session, i.e., initial treatment or touch-up treatment respectively.</description>
        </group>
        <group group_id="P2">
          <title>Group B-Restylane Volyme Treatment Arm</title>
          <description>Including treatment arm. A maximum dosage of 2 mL per treatment site (i.e., right and left midface respectively) is recommended at each treatment session, i.e., initial treatment or touch-up treatment respectively.</description>
        </group>
        <group group_id="P3">
          <title>Group B- Control Arm</title>
          <description>Including control arm Subjects assigned to the Control Group in Group B will not receive treatment at baseline but will return for routine follow-up for 12 months. At month 6 visit, subjects in Control Group will be offered a treatment and an optional touch-up treatment. A maximum dosage of 2 mL per treatment site (i.e., right and left midface respectively) is recommended at each treatment session, i.e., initial treatment or touch-up treatment respectively.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="111"/>
                <participants group_id="P3" count="37"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="108"/>
                <participants group_id="P3" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All summaries will be done separately for Group A (20subjects) and B(148 subjects). For statistical inference, only Group B will be used.</population>
      <group_list>
        <group group_id="B1">
          <title>Group A</title>
          <description>The first 2 eligible subjects for each Treating Investigator will receive treatment as Group A.</description>
        </group>
        <group group_id="B2">
          <title>Restylane Volyme Treatment Group of Group B</title>
          <description>Subjects assigned in this group will receive Restylane Volyme treatment at day 1.</description>
        </group>
        <group group_id="B3">
          <title>Control Group of Group B</title>
          <description>Subjects assigned in this group will receive no treatment at day 1, but at 6m visit.</description>
        </group>
        <group group_id="B4">
          <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="20"/>
            <count group_id="B2" value="111"/>
            <count group_id="B3" value="37"/>
            <count group_id="B4" value="168"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="109"/>
                    <measurement group_id="B3" value="37"/>
                    <measurement group_id="B4" value="166"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="46.3" spread="9.7"/>
                    <measurement group_id="B2" value="41.3" spread="10.2"/>
                    <measurement group_id="B3" value="41.2" spread="10.0"/>
                    <measurement group_id="B4" value="41.3" spread="10.1"/>
                  </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="20"/>
                    <measurement group_id="B2" value="104"/>
                    <measurement group_id="B3" value="32"/>
                    <measurement group_id="B4" value="156"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Chinese Han</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="111"/>
                    <measurement group_id="B3" value="37"/>
                    <measurement group_id="B4" value="168"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>China</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="111"/>
                    <measurement group_id="B3" value="37"/>
                    <measurement group_id="B4" value="168"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Responders</title>
        <description>Percentage of responders, defined by at least 1 point improvement from baseline on the MMVS on both sides of the face concurrently, as measured by the blinded evaluator at 6 months after last treatment in Treatment Group, and at 6 months after randomization in Control Group.&#xD;
MMVS is a Four-Point scale that assesses the fullness of the midface from Fairly Full (1) to Substantial Loss of Fullness (4) as described below. The blinded evaluator and treating investigator will rate the subject's right and left midface for severity of volume deficiency using the MMVS at all applicable study visits.</description>
        <time_frame>6 month</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>The first 2 eligible subjects for each Treating Investigator will receive Restylane Volyme treatment as Group A. The injection technique will be evaluated by the Sponsor and performed after the subjects in Group A for each site have received their first treatment. If treatments are found to be correctly performed, no further training is needed, there are no outstanding questions regarding the injection technique and no other corrective actions are identified, the enrolment in Group B can start for that site.</description>
          </group>
          <group group_id="O2">
            <title>Group B-treatment Arm</title>
            <description>Subject assigned in this group will receive Restylane Volyme treatment at D1.</description>
          </group>
          <group group_id="O3">
            <title>Group B-control Arm</title>
            <description>Subject assigned in this group will not receive Restylane Volyme treatment at D1 but on 6M visit.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Responders</title>
          <description>Percentage of responders, defined by at least 1 point improvement from baseline on the MMVS on both sides of the face concurrently, as measured by the blinded evaluator at 6 months after last treatment in Treatment Group, and at 6 months after randomization in Control Group.&#xD;
MMVS is a Four-Point scale that assesses the fullness of the midface from Fairly Full (1) to Substantial Loss of Fullness (4) as described below. The blinded evaluator and treating investigator will rate the subject's right and left midface for severity of volume deficiency using the MMVS at all applicable study visits.</description>
          <units>percentage of subjects</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="111"/>
                <count group_id="O3" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80" lower_limit="56.3" upper_limit="94.3"/>
                    <measurement group_id="O2" value="87.2" lower_limit="79.4" upper_limit="92.8"/>
                    <measurement group_id="O3" value="76.7" lower_limit="57.7" upper_limit="90.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 year.</time_frame>
      <desc>Each subject will be questioned about AEs at each clinical visit following the screening visit. The question asked will be &quot;Since your last clinical visit have you had any health problems?&quot; Information on AEs can also be obtained from signs and symptoms detected during each examination or from a laboratory test, observations by the study personnel, subject diaries or spontaneous reports from the subjects.</desc>
      <group_list>
        <group group_id="E1">
          <title>Group A</title>
          <description>The first 2 eligible subjects for each Treating Investigator will receive Restylane Volyme treatment as Group A. The injection technique will be evaluated by the Sponsor and performed after the subjects in Group A for each site have received their first treatment. If treatments are found to be correctly performed, no further training is needed, there are no outstanding questions regarding the injection technique and no other corrective actions are identified, the enrolment in Group B can start for that site.&#xD;
A maximum dosage of 2 mL per treatment site (i.e., right and left midface respectively) is recommended at each treatment session, i.e., initial treatment or touch-up treatment respectively.</description>
        </group>
        <group group_id="E2">
          <title>Group B-treatment Arm</title>
          <description>including treatment arm A maximum dosage of 2 mL per treatment site (i.e., right and left midface respectively) is recommended at each treatment session, i.e., initial treatment or touch-up treatment respectively.</description>
        </group>
        <group group_id="E3">
          <title>Group B-control Arm</title>
          <description>including control arm Subjects assigned to the Control Group in Group B will not receive treatment at baseline but will return for routine follow-up for 12 months. At month 6 visit, subjects in Control Group will be offered a treatment and an optional touch-up treatment.</description>
        </group>
      </group_list>
      <serious_events>
        <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="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="111"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Lung adenocarcinoma stage 0</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Skin papilloma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="111"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Head of Development</name_or_title>
      <organization>Q-Med AB</organization>
      <phone>+46184749000</phone>
      <email>reception.seupp@galderma.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/NCT03289052
org study id: 43CH1626
nct id: NCT03289052
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a randomized, evaluator-blinded, no-treatment controlled study in subjects with
      Midface Volume Deficit and/or Midface Contour Deficiency.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Percentage of Responders
time frame: 6 month
description: Percentage of responders, defined by at least 1 point improvement from baseline on the MMVS on both sides of the face concurrently, as measured by the blinded evaluator at 6 months after last treatment in Treatment Group, and at 6 months after randomization in Control Group.
MMVS is a Four-Point scale that assesses the fullness of the midface from Fairly Full (1) to Substantial Loss of Fullness (4) as described below. The blinded evaluator and treating investigator will rate the subject's right and left midface for severity of volume deficiency using the MMVS at all applicable study visits.
arm group label: Restylane Volyme
arm group type: Experimental
description: Single injection and optional touch up injection with Restylane Volyme in Midface
arm group label: No intervention arm
arm group type: No Intervention
description: No treatment
intervention type: Device
intervention name: Restylane Volyme
description: Subcutis injection
arm group label: Restylane Volyme
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 