<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/NCT04461678</url>
  </required_header>
  <id_info>
    <org_study_id>BDS-19CNHPV</org_study_id>
    <nct_id>NCT04461678</nct_id>
  </id_info>
  <brief_title>Clinical Trial for Registration of HPV Nucleic Acid Genotyping Assay Kit</brief_title>
  <official_title>Clinical Trial for Registration of HPV Nucleic Acid Genotyping Assay Kit</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Becton, Dickinson and Company</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Becton, Dickinson and Company</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>
      The objective of this study is to verify the clinical effectiveness of HPV Genotyping Nucleic&#xD;
      Acid Assay Kit. This is a multi-center clinical study involving at least three study centers,&#xD;
      each with screening sites. The protocol describes two study phases: Phase I is a baseline&#xD;
      study of the screened population and ASCUS referral population (if necessary), the data of&#xD;
      which will be submitted after the baseline study is completed; Phase II is a three-year&#xD;
      follow-up study of the screened population, the data of which will be submitted again after&#xD;
      the follow-up is completed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Baseline study of the screened population:&#xD;
&#xD;
      The total sample size of screened population is approximately 12,000 cases (all females ≥ 21&#xD;
      years of age). Two cervical cytology samples will be collected from each subject with a tube&#xD;
      of SurePath sample followed by a tube of PreservCyt sample. The 1st tube of SurePath&#xD;
      liquid-based cytology sample is used for cytology test and BD Onclarity Assay HPV detection.&#xD;
      Subjects with cytology test results ≥ ASCUS or positive HPV test results will be suggested to&#xD;
      return for baseline colposcopy within approximately 12 weeks. Subjects with unsatisfactory&#xD;
      cytology results may be recalled for a second sampling 2 months after the first collection of&#xD;
      the cervical sample. In case of visible lesions under colposcopy, a biopsy of tissues at the&#xD;
      site of the lesion will be performed (an ECC will be performed if necessary); in case of no&#xD;
      visible lesions, randomly biopsy and/or ECC will be performed if necessary. Patients with&#xD;
      histopathological findings ≥ CIN2 will complete the study (see Figure 1). In the baseline&#xD;
      colposcopy phase, if the subject is pregnant, the subject will be withdrawn from the study&#xD;
      without colposcopy performed.&#xD;
&#xD;
      Based on the age of the subjects, different cytology results, and Surepath BD Onclarity Assay&#xD;
      HPV results, a total of more than 500 PreservCyt samples will be selected for BD Onclarity&#xD;
      Assay test and the HPV test for control product. For inconsistent results, a third-party&#xD;
      sequencing method will be used to determine the final result.&#xD;
&#xD;
      SurePath sample and PreserveCyt sample collected from the same subject will be used for BD&#xD;
      OnclarityTM Assay test to compare the consistency of test results, at least 200 samples will&#xD;
      be enrolled only for this test. Subjects will exit the study after those HPV test without any&#xD;
      other test.&#xD;
&#xD;
      ASCUS referral population study Female subjects with known ASCUS cytology results will be&#xD;
      enrolled in the referral population (21-65 years old) if necessary. Female subjects with an&#xD;
      ASCUS cytology result will be recalled to sign the informed consent to participate in the&#xD;
      study and undergo colposcopy (within 12 weeks from the cytology sampling). For referral&#xD;
      population, the remaining cervical samples collected prior to enrollment for cytology test&#xD;
      will be tested with the BD Onclarity Assay HPV (see Figure 2). Such population is only used&#xD;
      for the assessment of ASCUS triage indications and does not enter the follow-up longitudinal&#xD;
      follow-up study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 23, 2020</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Anticipated">May 2025</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Verification of the accuracy of nucleic acid assay</measure>
    <time_frame>12 weeks</time_frame>
    <description>The results of HPV Assay of test product and reference product</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PLR and NLR in ASCUS population</measure>
    <time_frame>12 weeks</time_frame>
    <description>Clinical sensitivity (Sn), clinical specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of carcinogenic HPV+ in case of ≥CIN2.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>HPV risk of ≥ CIN2 in NILM 30+ population</measure>
    <time_frame>3 years</time_frame>
    <description>absolute risk and 95%CI of HPV+, HPV 16 / 18/45 +, HPV31 / 33_58 / 52; HPV51 / 35_39_68 / 56_59_66 + and HPV- in case of ≥ CIN2&#xD;
Relative risk and 95%CI of HPV+ and HPV- in case of ≥ CIN2&#xD;
Relative risk and 95%CI of HPV 16 / 18/45 and HPV- in case of ≥ CIN2&#xD;
Relative risk and 95%CI of HPV 31 / 33_58 / 52 and HPV- in case of ≥ CIN2&#xD;
Relative risk and 95%CI of HPV 51, 35 / 39 / 68, 56 / 59/66 and HPV- in case of ≥ CIN2&#xD;
Relative risk and 95%CI of HPV 16 / 18/45 + and HPV 31 / 33_58 / 52 + in case of ≥ CIN2&#xD;
Relative risk and 95%CI of HPV 16 / 18/45 + and HPV 51, 35 / 39 / 68, 56 / 59/66 + in case of ≥ CIN2&#xD;
Relative risk and 95%CI of HPV 31 / 33_58 / 52 + and HPV 51, 35 / 39 / 68, 56 / 59/66 + in case of ≥ CIN2</description>
  </primary_outcome>
  <primary_outcome>
    <measure>HPV risk of ≥ CIN2 in Primary screening</measure>
    <time_frame>3 years</time_frame>
    <description>Absolute risk and 95%CI of NILM, HPV-, HPV +, HPV16 / 18/45 +, HPV 31 / 33_58 / 52 +, HPV 51, 35 / 39 / 68, 56 / 59/66 + and HPV in case of ≥ CIN2&#xD;
Relative risk and 95%CI of NILM and HPV- in case of ≥ CIN2&#xD;
Relative risk and 95%CI of HPV+ and HPV- in case of ≥ CIN2&#xD;
Relative risk and 95%CI of HPV 16 / 18/45+ and HPV- in case of ≥ CIN2&#xD;
Relative risk and 95%CI of HPV 31 / 33_58 / 52 and HPV- in case of ≥ CIN2&#xD;
Relative risk and 95%CI of HPV 51, 35 / 39 / 68, 56 / 59/66 and HPV- in case of ≥ CIN2&#xD;
Relative risk and 95%CI of HPV 16 / 18/45 + and HPV 31 / 33_58 / 52 + in case of ≥ CIN2&#xD;
Relative risk and 95%CI of HPV 16 / 18/45 + and HPV 51, 35 / 39 / 68, 56 / 59/66 + in case of ≥ CIN2&#xD;
Relative risk and 95%CI of HPV 31 / 33_58 / 52 + and HPV 51, 35 / 39 / 68, 56 / 59/66 + in case of ≥ CIN2</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">12000</enrollment>
  <condition>Cervical Cancer</condition>
  <arm_group>
    <arm_group_label>Screening population and ASCUS referral population</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The screening population: Two cervical cytology samples will be collected from each subject. The 1st tube of SurePath liquid-based cytology sample is used for cytology test and BD Onclarity Assay HPV detection. Subjects with cytology test results ≥ ASCUS or positive HPV test results will be suggested to return for baseline colposcopy within approximately 12 weeks. In case of visible lesions under colposcopy, a biopsy of tissues at the site of the lesion will be performed; in case of no visible lesions, randombiopsy and/or ECC will be performed. Patients with histopathological results ≥ CIN2 will completed the study.&#xD;
ASCUS referral population: Female subjects with an ASCUS cytology result will be recalled undergo colposcopy, the remaining samples for cytology test collected prior to enrollment will be used for BD Onclarity Assay HPV test.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>HPV Genotyping Nucleic Acid Assay Kit</intervention_name>
    <description>The total sample size of screening population is approximately 12,000 cases (all females ≥ 21 years of age). Two cervical cytology samples will be collected from each subject with a tube of SurePath sample followed by a tube of PreservCyt sample. The 1st tube of SurePath liquid-based cytology sample is used for cytology test and BD Onclarity Assay HPV detection. Subjects with cytology test results ≥ ASCUS or positive HPV test results will be suggested to return for baseline colposcopy within approximately 12 weeks.</description>
    <arm_group_label>Screening population and ASCUS referral population</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female subjects ≥ 21 of age and &lt; 65 of age&#xD;
&#xD;
          -  Subjects who have signed the inform consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant subjects&#xD;
&#xD;
          -  Subjects who have had cervical cytology samples taken in the last 12 months&#xD;
&#xD;
          -  Subjects who have previously undergone a total hysterectomy&#xD;
&#xD;
          -  Subjects who have previously undergone cone resection, LEEP, cervical laser surgery,&#xD;
             cervical cryosurgery or uterine ablation within 3 years&#xD;
&#xD;
          -  Subjects who are participating in other clinical trials of cervical disease diagnostic&#xD;
             products&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shaokai Zhang</last_name>
    <role>Principal Investigator</role>
    <affiliation>Henan Cancer Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cancer Hospital Chinese Academy of Medical Science</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henan Cancer Hospital</name>
      <address>
        <city>Zhengzhou</city>
        <state>Henan</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Obstetrics&amp;Gynecology Hospital of Fudan University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Heping Hospital Affilated to Changzhi Medical College</name>
      <address>
        <city>Changzhi</city>
        <state>Shanxi</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women's Hospital School of Medicine Zhejiang University</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>June 30, 2020</study_first_submitted>
  <study_first_submitted_qc>July 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <last_update_submitted>February 28, 2023</last_update_submitted>
  <last_update_submitted_qc>February 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2023</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 Neoplasms</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/NCT04461678
org study id: BDS-19CNHPV
nct id: NCT04461678
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The objective of this study is to verify the clinical effectiveness of HPV Genotyping Nucleic
      Acid Assay Kit. This is a multi-center clinical study involving at least three study centers,
      each with screening sites. The protocol describes two study phases: Phase I is a baseline
      study of the screened population and ASCUS referral population (if necessary), the data of
      which will be submitted after the baseline study is completed; Phase II is a three-year
      follow-up study of the screened population, the data of which will be submitted again after
      the follow-up is completed.
Baseline study of the screened population:

      The total sample size of screened population is approximately 12,000 cases (all females ≥ 21
      years of age). Two cervical cytology samples will be collected from each subject with a tube
      of SurePath sample followed by a tube of PreservCyt sample. The 1st tube of SurePath
      liquid-based cytology sample is used for cytology test and BD Onclarity Assay HPV detection.
      Subjects with cytology test results ≥ ASCUS or positive HPV test results will be suggested to
      return for baseline colposcopy within approximately 12 weeks. Subjects with unsatisfactory
      cytology results may be recalled for a second sampling 2 months after the first collection of
      the cervical sample. In case of visible lesions under colposcopy, a biopsy of tissues at the
      site of the lesion will be performed (an ECC will be performed if necessary); in case of no
      visible lesions, randomly biopsy and/or ECC will be performed if necessary. Patients with
      histopathological findings ≥ CIN2 will complete the study (see Figure 1). In the baseline
      colposcopy phase, if the subject is pregnant, the subject will be withdrawn from the study
      without colposcopy performed.

      Based on the age of the subjects, different cytology results, and Surepath BD Onclarity Assay
      HPV results, a total of more than 500 PreservCyt samples will be selected for BD Onclarity
      Assay test and the HPV test for control product. For inconsistent results, a third-party
      sequencing method will be used to determine the final result.

      SurePath sample and PreserveCyt sample collected from the same subject will be used for BD
      OnclarityTM Assay test to compare the consistency of test results, at least 200 samples will
      be enrolled only for this test. Subjects will exit the study after those HPV test without any
      other test.

      ASCUS referral population study Female subjects with known ASCUS cytology results will be
      enrolled in the referral population (21-65 years old) if necessary. Female subjects with an
      ASCUS cytology result will be recalled to sign the informed consent to participate in the
      study and undergo colposcopy (within 12 weeks from the cytology sampling). For referral
      population, the remaining cervical samples collected prior to enrollment for cytology test
      will be tested with the BD Onclarity Assay HPV (see Figure 2). Such population is only used
      for the assessment of ASCUS triage indications and does not enter the follow-up longitudinal
      follow-up study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Verification of the accuracy of nucleic acid assay
time frame: 12 weeks
description: The results of HPV Assay of test product and reference product
measure: PLR and NLR in ASCUS population
time frame: 12 weeks
description: Clinical sensitivity (Sn), clinical specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of carcinogenic HPV+ in case of ≥CIN2.
measure: HPV risk of ≥ CIN2 in NILM 30+ population
time frame: 3 years
description: absolute risk and 95%CI of HPV+, HPV 16 / 18/45 +, HPV31 / 33_58 / 52; HPV51 / 35_39_68 / 56_59_66 + and HPV- in case of ≥ CIN2
Relative risk and 95%CI of HPV+ and HPV- in case of ≥ CIN2
Relative risk and 95%CI of HPV 16 / 18/45 and HPV- in case of ≥ CIN2
Relative risk and 95%CI of HPV 31 / 33_58 / 52 and HPV- in case of ≥ CIN2
Relative risk and 95%CI of HPV 51, 35 / 39 / 68, 56 / 59/66 and HPV- in case of ≥ CIN2
Relative risk and 95%CI of HPV 16 / 18/45 + and HPV 31 / 33_58 / 52 + in case of ≥ CIN2
Relative risk and 95%CI of HPV 16 / 18/45 + and HPV 51, 35 / 39 / 68, 56 / 59/66 + in case of ≥ CIN2
Relative risk and 95%CI of HPV 31 / 33_58 / 52 + and HPV 51, 35 / 39 / 68, 56 / 59/66 + in case of ≥ CIN2
measure: HPV risk of ≥ CIN2 in Primary screening
time frame: 3 years
description: Absolute risk and 95%CI of NILM, HPV-, HPV +, HPV16 / 18/45 +, HPV 31 / 33_58 / 52 +, HPV 51, 35 / 39 / 68, 56 / 59/66 + and HPV in case of ≥ CIN2
Relative risk and 95%CI of NILM and HPV- in case of ≥ CIN2
Relative risk and 95%CI of HPV+ and HPV- in case of ≥ CIN2
Relative risk and 95%CI of HPV 16 / 18/45+ and HPV- in case of ≥ CIN2
Relative risk and 95%CI of HPV 31 / 33_58 / 52 and HPV- in case of ≥ CIN2
Relative risk and 95%CI of HPV 51, 35 / 39 / 68, 56 / 59/66 and HPV- in case of ≥ CIN2
Relative risk and 95%CI of HPV 16 / 18/45 + and HPV 31 / 33_58 / 52 + in case of ≥ CIN2
Relative risk and 95%CI of HPV 16 / 18/45 + and HPV 51, 35 / 39 / 68, 56 / 59/66 + in case of ≥ CIN2
Relative risk and 95%CI of HPV 31 / 33_58 / 52 + and HPV 51, 35 / 39 / 68, 56 / 59/66 + in case of ≥ CIN2
arm group label: Screening population and ASCUS referral population
arm group type: Experimental
description: The screening population: Two cervical cytology samples will be collected from each subject. The 1st tube of SurePath liquid-based cytology sample is used for cytology test and BD Onclarity Assay HPV detection. Subjects with cytology test results ≥ ASCUS or positive HPV test results will be suggested to return for baseline colposcopy within approximately 12 weeks. In case of visible lesions under colposcopy, a biopsy of tissues at the site of the lesion will be performed; in case of no visible lesions, randombiopsy and/or ECC will be performed. Patients with histopathological results ≥ CIN2 will completed the study.
ASCUS referral population: Female subjects with an ASCUS cytology result will be recalled undergo colposcopy, the remaining samples for cytology test collected prior to enrollment will be used for BD Onclarity Assay HPV test.
intervention type: Diagnostic Test
intervention name: HPV Genotyping Nucleic Acid Assay Kit
description: The total sample size of screening population is approximately 12,000 cases (all females ≥ 21 years of age). Two cervical cytology samples will be collected from each subject with a tube of SurePath sample followed by a tube of PreservCyt sample. The 1st tube of SurePath liquid-based cytology sample is used for cytology test and BD Onclarity Assay HPV detection. Subjects with cytology test results ≥ ASCUS or positive HPV test results will be suggested to return for baseline colposcopy within approximately 12 weeks.
arm group label: Screening population and ASCUS referral population
criteria: 
gender: Female
minimum age: 21 Years
maximum age: 64 Years
healthy volunteers: No
last name: Shaokai Zhang
role: Principal Investigator
affiliation: Henan Cancer Hospital
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
responsible party type: Sponsor
mesh term: Uterine Cervical Neoplasms
sharing ipd: No