xml: <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/NCT06013332</url>
    </required_header>
    <id_info>
      <org_study_id>PBF-PLLA-001</org_study_id>
      <nct_id>NCT06013332</nct_id>
    </id_info>
    <brief_title>Polymeric Microspheres vs Sculptra® in the Treatment of Moderate to Severe Nasolabial Folds</brief_title>
    <official_title>A Controlled, Randomized, Double-Blinded, Intra-Subject, Multicenter, Prospective, Clinical Study to Investigate the Non-Inferiority Between the Polymeric Microspheres and Sculptra® in the Treatment of Moderate to Severe Nasolabial Folds</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Taipei Medical University Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Taipei Medical University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Panion &amp; BF Biotech Inc.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Taipei Medical University Hospital</source>
    <oversight_info>
      <has_dmc>Yes</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 single-dose, randomized, double-blind, active-controlled, split-face, multiple&#xD;
        centers, non-inferiority study. Approximately 50 nasolabial fold subjects will be enrolled.&#xD;
        Each enrolled subject will be randomized equally into one of the following groups:&#xD;
  &#xD;
          1. Group 1: right face will be injected with PBF PLLA microsphere, and left face with&#xD;
             Sculptra®&#xD;
  &#xD;
          2. Group 2: right face will be injected with Sculptra® and left face with PBF PLLA&#xD;
             microsphere Subjects will be administrated on Visit 1 by applying PBF PLLA microsphere&#xD;
             on one side of face and Sculptra® on the other.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">June 2025</completion_date>
    <primary_completion_date type="Anticipated">June 2024</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>Crossover Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Care Provider, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Delta of the WAS score between the Baseline and 26 weeks after treatment assessed by the Independent Evaluators of PLLA(PBF) versus Sculptra®</measure>
      <time_frame>26 weeks</time_frame>
      <description>Wrinkle Assessment Scale (WAS): 0 No wrinkles; 1 Just perceptible wrinkle; 2 Shallow wrinkles; 3 Moderately deep wrinkle; 4 deep wrinkle, well-defined edges; 5 Very deep wrinkle, redundant fold</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall operation time during subcutaneous injection of PLLA(PBF) versus Sculptra®</measure>
      <time_frame>First week from the Start of administration to the end of administration</time_frame>
      <description>To compare the operational smoothness for physicians between the two medical devices</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Delta of the WAS score assessed by the Investigator between each follow-up visit (13th, 26th, 39th and 52nd week post-administration) and the Baseline of PLLA(PBF) versus Sculptra®</measure>
      <time_frame>13th, 26th, 39th and 52nd week post-administration</time_frame>
      <description>Wrinkle Assessment Scale (WAS): 0 No wrinkles; 1 Just perceptible wrinkle; 2 Shallow wrinkles; 3 Moderately deep wrinkle; 4 deep wrinkle, well-defined edges; 5 Very deep wrinkle, redundant fold</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Delta of the WSRS score between the Baseline and 26 weeks after treatment assessed by the Independent Evaluators of PLLA(PBF) versus Sculptra®</measure>
      <time_frame>26 weeks</time_frame>
      <description>Grade 1: No visible nasolabial fold; continuous skin line Grade 2: Shallow but visible nasolabial fold with a slight indentation; minor facial feature; the implant is expected to produce a slight improvement in appearance Grade 3: Moderately deep nasolabial folds; clear facial feature visible at normal appearance but not when stretched; excellent correction is expected with injectable implant Grade 4: Very long and deep nasolabial folds; prominent facial feature; 2mm visible fold when stretched; significant improvement is expected with injectable implant Grade 5: Extremely deep and long nasolabial folds, detrimental to facial appearance; 2-4mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Delta of the WSRS score assessed by the Investigator between each follow-up visit (13th, 26th, 39th and 52nd week post-administration) and the Baseline of PLLA(PBF) versus Sculptra®</measure>
      <time_frame>13th, 26th, 39th and 52nd week post-administration</time_frame>
      <description>Grade 1: No visible nasolabial fold; continuous skin line Grade 2: Shallow but visible nasolabial fold with a slight indentation; minor facial feature; the implant is expected to produce a slight improvement in appearance Grade 3: Moderately deep nasolabial folds; clear facial feature visible at normal appearance but not when stretched; excellent correction is expected with injectable implant Grade 4: Very long and deep nasolabial folds; prominent facial feature; 2mm visible fold when stretched; significant improvement is expected with injectable implant Grade 5: Extremely deep and long nasolabial folds, detrimental to facial appearance; 2-4mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of responders based on the intra-individual improvement of at least one grade in the WAS score compared to baseline assessed by the Investigator of PLLA(PBF) versus Sculptra®</measure>
      <time_frame>13th, 26th, 39th and 52nd week post-administration</time_frame>
      <description>Wrinkle Assessment Scale (WAS): 0 No wrinkles; 1 Just perceptible wrinkle; 2 Shallow wrinkles; 3 Moderately deep wrinkle; 4 deep wrinkle, well-defined edges; 5 Very deep wrinkle, redundant fold</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of responders based on the intra-individual improvement of at least one grade in the WSRS score compared to baseline assessed by the Investigator of PLLA(PBF) versus Sculptra®</measure>
      <time_frame>13th, 26th, 39th and 52nd week post-administration</time_frame>
      <description>Grade 1: No visible nasolabial fold; continuous skin line Grade 2: Shallow but visible nasolabial fold with a slight indentation; minor facial feature; the implant is expected to produce a slight improvement in appearance Grade 3: Moderately deep nasolabial folds; clear facial feature visible at normal appearance but not when stretched; excellent correction is expected with injectable implant Grade 4: Very long and deep nasolabial folds; prominent facial feature; 2mm visible fold when stretched; significant improvement is expected with injectable implant Grade 5: Extremely deep and long nasolabial folds, detrimental to facial appearance; 2-4mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of subjects scored either 'Much Improved' or 'Improved' on GAIS evaluated by the Investigator for PLLA(PBF) versus Sculptra®</measure>
      <time_frame>13th, 26th, 39th and 52nd week post-administration</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Subject's satisfaction score (Subjective 5-point scale with 1 being 'very satisfied' and 5 being 'very dissatisfied') of PLLA(PBF) versus Sculptra®</measure>
      <time_frame>13th, 26th, 39th and 52nd week post-administration</time_frame>
    </secondary_outcome>
    <other_outcome>
      <measure>Post injection treatment responses (From common treatment responses diary card) for safety evaluation of PBF PLLA microsphere versus Sculptra®</measure>
      <time_frame>During 2 weeks post-administration</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Assessment of injection site pain of PBF PLLA microsphere versus Sculptra® by using Visual Analogue Scale (VAS) score</measure>
      <time_frame>immediately after injection and at 5-, 15- and 30- minute post-administration</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Compare the treatment related adverse event</measure>
      <time_frame>During 52 weeks post-administration</time_frame>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Nasolabial Fold Wrinkles</condition>
    <arm_group>
      <arm_group_label>Group 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>right face will be injected with PBF PLLA microsphere, and left face with Sculptra®</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Group 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>right face will be injected with Sculptra® and left face with PBF PLLA microsphere</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>PBF PLLA microsphere (injectable poly-L-lactic acid)</intervention_name>
      <description>Poly-L-lactic acid (PLLA) is a collagen stimulator, helps restore the deep, underlying structure of the skin to diminish facial wrinkles. PLLA microparticles are absorbable for human body, and it works with human body within the deep dermis to help revitalize collagen production and help restore human skin's inner structure and volume. PLLA can rebuilt collagen strands begin gradually helping to restore facial volume and the look of fullness to wrinkles and folds.</description>
      <arm_group_label>Group 1</arm_group_label>
      <arm_group_label>Group 2</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Sculptra®</intervention_name>
      <description>Sculptra®</description>
      <arm_group_label>Group 1</arm_group_label>
      <arm_group_label>Group 2</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Participant whose age is ≥ 18 and ≤ 65 years old.&#xD;
  &#xD;
            2. Participant who is able to read, understand, sign, and date a written informed consent&#xD;
               form (ICF) before study participation at screening.&#xD;
  &#xD;
            3. Participant is able to understand and comply with protocol requirements and&#xD;
               instructions and likely to complete the study as planned.&#xD;
  &#xD;
            4. Participant who has moderate to severe nasolabial folds on two sides of face, WAS&#xD;
               Score ≥ 3. WAS Score is determined by investigator.&#xD;
  &#xD;
            5. Participant whose difference in WAS score of nasolabial folds on two sides of face ≤&#xD;
               1. WAS Score is determined by investigator.&#xD;
  &#xD;
            6. Participant's skin condition is considered by Investigator suitable for the treatment&#xD;
               of Poly-L-lactic Acid (PLLA).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          -&#xD;
  &#xD;
          1. Participant who has previous tissue augmenting therapy, contouring or revitalization&#xD;
          treatment in or near the treatment area prior to the Baseline visit.&#xD;
  &#xD;
            1. Treatment with collagen or hyaluronic acid (HA) in the last 12 months.&#xD;
  &#xD;
            2. Had facelift treatment (high intensity focused ultrasound, radio frequency, or thread)&#xD;
               within 12 months.&#xD;
  &#xD;
            3. Had face laser treatment within 6 months.&#xD;
  &#xD;
            4. Had been treated with Calcium Hydroxyapatite (CaHA), PLLA or permanent&#xD;
               (non-biodegradable).&#xD;
  &#xD;
          2. Participant who has severe allergies with a history of severe reactions (anaphylaxis) or&#xD;
          multiple severe allergies or has known/previous allergy or hypersensitivity to any of the&#xD;
          PLLA, other constituents of PBF PLLA microsphere or Sculptra®, or drugs containing&#xD;
          lidocaine such as Lidiprine Cream and its constituents. 3. Participant who has obvious&#xD;
          defects, trauma, or scars near the treatment area.&#xD;
  &#xD;
          4. Participant who has been diagnosed head cancer in the last 3 years. 5. Participant who&#xD;
          has trauma, open wound, active skin disease or inflammation at the injection site.&#xD;
  &#xD;
          6. Participant who has serious systematic disease that judged by Investigator which is not&#xD;
          suitable for the treatment.&#xD;
  &#xD;
          7. Participant who has connective tissue disease, bleeding disorders, active hepatitis,&#xD;
          immune deficiency disease, disease such as cancer, stroke and/or myocardial infarction and&#xD;
          on any immunosuppressive therapy.&#xD;
  &#xD;
          8. Participant who previously had or have risks factors for hypertrophic scarring or keloid&#xD;
          formation near the treatment area.&#xD;
  &#xD;
          9. Participant who has used immune system suppression drugs, steroids, anti-inflammatory&#xD;
          drugs, anticoagulant drugs, or aspirin within 7 days before treatment.&#xD;
  &#xD;
          10. Female participant who is pregnant or lactating.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Hsiou-Hsin Tsai, M.D. PhD.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Taipei Medical University Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Hsiou-Hsin Tsai, M.D. PhD.</last_name>
      <phone>+886-2-2737-2181</phone>
      <email>tsaihh2000@yahoo.com.tw</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Pu-Sheng Wei, PhD.</last_name>
      <email>d301106004@tmu.edu.tw</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 13, 2023</study_first_submitted>
    <study_first_submitted_qc>August 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>August 25, 2023</last_update_submitted>
    <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Taipei Medical University Hospital</investigator_affiliation>
      <investigator_full_name>Hsiou-Hsin Tsai</investigator_full_name>
      <investigator_title>Visiting Staff</investigator_title>
    </responsible_party>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06013332
  org study id: PBF-PLLA-001
  nct id: NCT06013332
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This is a single-dose, randomized, double-blind, active-controlled, split-face, multiple
        centers, non-inferiority study. Approximately 50 nasolabial fold subjects will be enrolled.
        Each enrolled subject will be randomized equally into one of the following groups:
  
          1. Group 1: right face will be injected with PBF PLLA microsphere, and left face with
             Sculptra®
  
          2. Group 2: right face will be injected with Sculptra® and left face with PBF PLLA
             microsphere Subjects will be administrated on Visit 1 by applying PBF PLLA microsphere
             on one side of face and Sculptra® on the other.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Treatment
  masking: Triple (Participant, Care Provider, Investigator)
  measure: Delta of the WAS score between the Baseline and 26 weeks after treatment assessed by the Independent Evaluators of PLLA(PBF) versus Sculptra®
  time frame: 26 weeks
  description: Wrinkle Assessment Scale (WAS): 0 No wrinkles; 1 Just perceptible wrinkle; 2 Shallow wrinkles; 3 Moderately deep wrinkle; 4 deep wrinkle, well-defined edges; 5 Very deep wrinkle, redundant fold
  measure: Overall operation time during subcutaneous injection of PLLA(PBF) versus Sculptra®
  time frame: First week from the Start of administration to the end of administration
  description: To compare the operational smoothness for physicians between the two medical devices
  measure: Delta of the WAS score assessed by the Investigator between each follow-up visit (13th, 26th, 39th and 52nd week post-administration) and the Baseline of PLLA(PBF) versus Sculptra®
  time frame: 13th, 26th, 39th and 52nd week post-administration
  description: Wrinkle Assessment Scale (WAS): 0 No wrinkles; 1 Just perceptible wrinkle; 2 Shallow wrinkles; 3 Moderately deep wrinkle; 4 deep wrinkle, well-defined edges; 5 Very deep wrinkle, redundant fold
  measure: Delta of the WSRS score between the Baseline and 26 weeks after treatment assessed by the Independent Evaluators of PLLA(PBF) versus Sculptra®
  time frame: 26 weeks
  description: Grade 1: No visible nasolabial fold; continuous skin line Grade 2: Shallow but visible nasolabial fold with a slight indentation; minor facial feature; the implant is expected to produce a slight improvement in appearance Grade 3: Moderately deep nasolabial folds; clear facial feature visible at normal appearance but not when stretched; excellent correction is expected with injectable implant Grade 4: Very long and deep nasolabial folds; prominent facial feature; 2mm visible fold when stretched; significant improvement is expected with injectable implant Grade 5: Extremely deep and long nasolabial folds, detrimental to facial appearance; 2-4mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone
  measure: Delta of the WSRS score assessed by the Investigator between each follow-up visit (13th, 26th, 39th and 52nd week post-administration) and the Baseline of PLLA(PBF) versus Sculptra®
  time frame: 13th, 26th, 39th and 52nd week post-administration
  description: Grade 1: No visible nasolabial fold; continuous skin line Grade 2: Shallow but visible nasolabial fold with a slight indentation; minor facial feature; the implant is expected to produce a slight improvement in appearance Grade 3: Moderately deep nasolabial folds; clear facial feature visible at normal appearance but not when stretched; excellent correction is expected with injectable implant Grade 4: Very long and deep nasolabial folds; prominent facial feature; 2mm visible fold when stretched; significant improvement is expected with injectable implant Grade 5: Extremely deep and long nasolabial folds, detrimental to facial appearance; 2-4mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone
  measure: Percentage of responders based on the intra-individual improvement of at least one grade in the WAS score compared to baseline assessed by the Investigator of PLLA(PBF) versus Sculptra®
  time frame: 13th, 26th, 39th and 52nd week post-administration
  description: Wrinkle Assessment Scale (WAS): 0 No wrinkles; 1 Just perceptible wrinkle; 2 Shallow wrinkles; 3 Moderately deep wrinkle; 4 deep wrinkle, well-defined edges; 5 Very deep wrinkle, redundant fold
  measure: Percentage of responders based on the intra-individual improvement of at least one grade in the WSRS score compared to baseline assessed by the Investigator of PLLA(PBF) versus Sculptra®
  time frame: 13th, 26th, 39th and 52nd week post-administration
  description: Grade 1: No visible nasolabial fold; continuous skin line Grade 2: Shallow but visible nasolabial fold with a slight indentation; minor facial feature; the implant is expected to produce a slight improvement in appearance Grade 3: Moderately deep nasolabial folds; clear facial feature visible at normal appearance but not when stretched; excellent correction is expected with injectable implant Grade 4: Very long and deep nasolabial folds; prominent facial feature; 2mm visible fold when stretched; significant improvement is expected with injectable implant Grade 5: Extremely deep and long nasolabial folds, detrimental to facial appearance; 2-4mm visible V-shaped fold when stretched; unlikely to have satisfactory correction with injectable implant alone
  measure: Number of subjects scored either 'Much Improved' or 'Improved' on GAIS evaluated by the Investigator for PLLA(PBF) versus Sculptra®
  time frame: 13th, 26th, 39th and 52nd week post-administration
  measure: Subject's satisfaction score (Subjective 5-point scale with 1 being 'very satisfied' and 5 being 'very dissatisfied') of PLLA(PBF) versus Sculptra®
  time frame: 13th, 26th, 39th and 52nd week post-administration
  measure: Post injection treatment responses (From common treatment responses diary card) for safety evaluation of PBF PLLA microsphere versus Sculptra®
  time frame: During 2 weeks post-administration
  measure: Assessment of injection site pain of PBF PLLA microsphere versus Sculptra® by using Visual Analogue Scale (VAS) score
  time frame: immediately after injection and at 5-, 15- and 30- minute post-administration
  measure: Compare the treatment related adverse event
  time frame: During 52 weeks post-administration
  arm group label: Group 1
  arm group type: Experimental
  description: right face will be injected with PBF PLLA microsphere, and left face with Sculptra®
  arm group label: Group 2
  arm group type: Experimental
  description: right face will be injected with Sculptra® and left face with PBF PLLA microsphere
  intervention type: Device
  intervention name: PBF PLLA microsphere (injectable poly-L-lactic acid)
  description: Poly-L-lactic acid (PLLA) is a collagen stimulator, helps restore the deep, underlying structure of the skin to diminish facial wrinkles. PLLA microparticles are absorbable for human body, and it works with human body within the deep dermis to help revitalize collagen production and help restore human skin's inner structure and volume. PLLA can rebuilt collagen strands begin gradually helping to restore facial volume and the look of fullness to wrinkles and folds.
  arm group label: Group 1
  arm group label: Group 2
  intervention type: Device
  intervention name: Sculptra®
  description: Sculptra®
  arm group label: Group 1
  arm group label: Group 2
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Hsiou-Hsin Tsai, M.D. PhD.
  role: Principal Investigator
  affiliation: Taipei Medical University Hospital
  last name: Hsiou-Hsin Tsai, M.D. PhD.
  phone: +886-2-2737-2181
  email: tsaihh2000@yahoo.com.tw
  last name: Pu-Sheng Wei, PhD.
  email: d301106004@tmu.edu.tw
  responsible party type: Principal Investigator
  investigator affiliation: Taipei Medical University Hospital
  investigator full name: Hsiou-Hsin Tsai
  investigator title: Visiting Staff