<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/NCT04484415</url>
  </required_header>
  <id_info>
    <org_study_id>YHGT-CEV-R1</org_study_id>
    <nct_id>NCT04484415</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Cevira® in Patients With Cervical Histologic High-grade Squamous Intraepithelial Lesions (HSIL)</brief_title>
  <acronym>APRICITY</acronym>
  <official_title>A Double Blind, Prospective, Randomized, Placebo Controlled, Multi-center Phase 3 Study to Evaluate Efficacy and Safety of Cevira® in Patients With Cervical Histologic High-grade Squamous Intraepithelial Lesions (HSIL)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Asieris MediTech (Hong Kong) Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jiangsu Yahong Meditech Co., Ltd aka Asieris</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>
      A double blind, prospective, randomized, placebo controlled, multi-center phase 3 study to&#xD;
      evaluate efficacy and safety of Cevira® in patients with cervical histologic high-grade&#xD;
      squamous intraepithelial lesions (HSIL).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To evaluate the efficacy and safety of Cevira® compared to placebo in treatment of patients&#xD;
      with cervical histologic HSIL.A total of 384 subjects will be enrolled globally, among which,&#xD;
      300 subjects of them will be enrolled in China.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 10, 2020</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>Phase 3</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The proportion of responders at 6 months after first treatment</measure>
    <time_frame>6 months</time_frame>
    <description>A responder is defined as follows:&#xD;
Normal histology; or&#xD;
LSIL histology and clearance of baseline HPV</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The proportion of HPV positive patients with clearance of baseline HPV at 6 months after first treatment.</measure>
    <time_frame>6 months</time_frame>
    <description>The proportion of HPV positive patients with clearance of baseline HPV at 6 months after first treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of HPV16 positive patients with clearance of HPV16 at 6 months after first treatment.</measure>
    <time_frame>6 months</time_frame>
    <description>The proportion of HPV16 positive patients with clearance of HPV16 at 6 months after first treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of HPV16 and/or HPV18 positive patients with clearance of baseline HPV at 6 months after first treatment.</measure>
    <time_frame>6 months</time_frame>
    <description>The proportion of HPV16 and/or HPV18 positive patients with clearance of baseline HPV at 6 months after first treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients with histologic regression, defined as LSIL or normal histology, at 6 months after first treatment.</measure>
    <time_frame>6 months</time_frame>
    <description>The proportion of patients with histologic regression, defined as LSIL or normal histology, at 6 months after first treatment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">402</enrollment>
  <condition>Cervical Intraepithelial Neoplasia Grade 2/3</condition>
  <arm_group>
    <arm_group_label>Cevira® treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The Cevira® treatment is an integrated combination of drug and device</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo ointment</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo ointment contains only vehicle, and is similar in appearance and consistence as the Cevira® ointment. The placebo device is identical in appearance as the Cevira® device, but does not provide light.</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Cevira®</intervention_name>
    <description>The device is a single-use, disposable, LED-based red light source. The device will automatically switch on the light 5 hours after administration, and provide continuous photoactivation of 125 J/cm2 over 4.6 hours before automatically shutting down.</description>
    <arm_group_label>Cevira® treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>The placebo device is identical in appearance as the Cevira® device, but does not provide light.</description>
    <arm_group_label>Placebo ointment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Biopsy-confirmed HSIL histology determined by a panel of 3 pathologists from a central&#xD;
             laboratory in each region (China, US, and Europe);&#xD;
&#xD;
          2. Adequate colposcopy including:&#xD;
&#xD;
               1. visualization of entire cervical transformation zone including the squamocolumnar&#xD;
                  junction&#xD;
&#xD;
               2. visualization of entire lesion margin&#xD;
&#xD;
          3. Colposcopically visible lesion after biopsy, before treatment (Note: To ensure a&#xD;
             colposcopically visible lesion after biopsy, the lesion should cover approximately 15%&#xD;
             of the uterine cervix before biopsy)&#xD;
&#xD;
          4. Average sized uterine cervix suitable for application of the Cevira® device&#xD;
&#xD;
          5. Use of adequate birth control until completion of the 6 month assessment visit&#xD;
&#xD;
          6. Age 18 or older (Note: Patients aged 18-20 should not be actively recruited)&#xD;
&#xD;
          7. Signed written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Biopsy-confirmed HSIL (CIN3) histology with a total lesion area covering more than&#xD;
             half of the uterine cervix area&#xD;
&#xD;
          2. Invasive cervical cancer&#xD;
&#xD;
          3. Adenocarcinoma in situ, or other glandular intraepithelial lesions&#xD;
&#xD;
          4. Lesion(s) extending to the cervical canal (as clinically indicated and whether to&#xD;
             perform endocervical curettage [ECC] test at the discretion of the investigators)&#xD;
&#xD;
          5. Lesion(s) extending to the vaginal vault&#xD;
&#xD;
          6. Current severe pelvic inflammatory disease, severe cervicitis, or other severe&#xD;
             gynecological infection as per colposcopy and clinical examination&#xD;
&#xD;
          7. Vaginal bleeding at time of treatment at the discretion of the investigator&#xD;
&#xD;
          8. Pregnancy&#xD;
&#xD;
          9. Nursing&#xD;
&#xD;
         10. Childbirth or miscarriage within six weeks of enrolment&#xD;
&#xD;
         11. Patients who previously received surgical treatment, have incomplete cervical&#xD;
             structure and have recurrent HSIL; or patients who received other treatment after the&#xD;
             confirmed diagnosis of HSIL&#xD;
&#xD;
         12. History of toxic shock syndrome&#xD;
&#xD;
         13. Known or suspected porphyria&#xD;
&#xD;
         14. Known allergy to hexaminolevulinate or similar compounds (e.g. methyl aminolevulinate&#xD;
             or aminolevulinic acid)&#xD;
&#xD;
         15. Known allergy to silicone&#xD;
&#xD;
         16. Use of heart pacemaker&#xD;
&#xD;
         17. Participation in other therapeutic clinical trials using investigational agents either&#xD;
             concurrently or within the last 30 days&#xD;
&#xD;
         18. Patients that in the investigator's opinion are not suitable for participation&#xD;
&#xD;
         19. Patient is the investigator or any sub-investigator, research assistant, pharmacist,&#xD;
             study coordinator, other staff or relative thereof directly involved in the conduct of&#xD;
             the study&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jinghe Lang, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking Union Medical College Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>John Zhuang, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Asieris MediTech (Hong Kong) Co., Ltd.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Peking Union Medical College Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>July 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>August 11, 2022</last_update_submitted>
  <last_update_submitted_qc>August 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uterine Cervical Dysplasia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT04484415
org study id: YHGT-CEV-R1
nct id: NCT04484415
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A double blind, prospective, randomized, placebo controlled, multi-center phase 3 study to
      evaluate efficacy and safety of Cevira® in patients with cervical histologic high-grade
      squamous intraepithelial lesions (HSIL).
To evaluate the efficacy and safety of Cevira® compared to placebo in treatment of patients
      with cervical histologic HSIL.A total of 384 subjects will be enrolled globally, among which,
      300 subjects of them will be enrolled in China.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The proportion of responders at 6 months after first treatment
time frame: 6 months
description: A responder is defined as follows:
Normal histology; or
LSIL histology and clearance of baseline HPV
measure: The proportion of HPV positive patients with clearance of baseline HPV at 6 months after first treatment.
time frame: 6 months
description: The proportion of HPV positive patients with clearance of baseline HPV at 6 months after first treatment.
measure: The proportion of HPV16 positive patients with clearance of HPV16 at 6 months after first treatment.
time frame: 6 months
description: The proportion of HPV16 positive patients with clearance of HPV16 at 6 months after first treatment.
measure: The proportion of HPV16 and/or HPV18 positive patients with clearance of baseline HPV at 6 months after first treatment.
time frame: 6 months
description: The proportion of HPV16 and/or HPV18 positive patients with clearance of baseline HPV at 6 months after first treatment.
measure: The proportion of patients with histologic regression, defined as LSIL or normal histology, at 6 months after first treatment.
time frame: 6 months
description: The proportion of patients with histologic regression, defined as LSIL or normal histology, at 6 months after first treatment.
arm group label: Cevira® treatment
arm group type: Experimental
description: The Cevira® treatment is an integrated combination of drug and device
arm group label: Placebo ointment
arm group type: Placebo Comparator
description: The placebo ointment contains only vehicle, and is similar in appearance and consistence as the Cevira® ointment. The placebo device is identical in appearance as the Cevira® device, but does not provide light.
intervention type: Combination Product
intervention name: Cevira®
description: The device is a single-use, disposable, LED-based red light source. The device will automatically switch on the light 5 hours after administration, and provide continuous photoactivation of 125 J/cm2 over 4.6 hours before automatically shutting down.
arm group label: Cevira® treatment
intervention type: Combination Product
intervention name: Placebo
description: The placebo device is identical in appearance as the Cevira® device, but does not provide light.
arm group label: Placebo ointment
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Jinghe Lang, MD,PhD
role: Principal Investigator
affiliation: Peking Union Medical College Hospital
last name: John Zhuang, PhD
role: Study Chair
affiliation: Asieris MediTech (Hong Kong) Co., Ltd.
facility: 
country: China
responsible party type: Sponsor
mesh term: Uterine Cervical Dysplasia
sharing ipd: No