<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/NCT03296397</url>
  </required_header>
  <id_info>
    <org_study_id>P150957</org_study_id>
    <nct_id>NCT03296397</nct_id>
  </id_info>
  <brief_title>Efficacy of Quadrivalent HPV Vaccine to Prevent Relapses of Genital Warts After Initial Therapeutic Response</brief_title>
  <acronym>CONDYVAC</acronym>
  <official_title>Efficacy Study of the Quadrivalent Human Papilloma Virus (HPV) Vaccine to Prevent Recurrence of External Genital Warts (EGW) in Patients Who Were Cured in the First Place</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</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>
      External genital warts (EGW) are a frequent disease (typical yearly incidence of 100 to 200&#xD;
      new cases per 100.000 person-years, typical prevalence of 1 to 4% of the sexually active&#xD;
      population), with a heavy toll on patients' quality of life: low self-esteem and severe&#xD;
      impairment of sexual well-being are common consequences. Treatments are painful and take time&#xD;
      to achieve cure because of low complete remission (20 to 60%) and high recurrence rates (10&#xD;
      to 40%, 30% on average). Finding new means to reduce these recurrence rates thus seems&#xD;
      justified. Infection with Human Papillomavirus (HPV) is responsible for EGW,other warts and&#xD;
      some epithelial cancers. Out of two currently available HPV vaccines (Cervarix and&#xD;
      Gardasil®), only Gardasil® is &quot; quadrivalent &quot; i.e. contains virus like particles imparting&#xD;
      protection versus 4 genotypes of HPV, 2 of them responsible of most cancers and pre cancers&#xD;
      of the cervix (HPV 16 and 18), and 2 for 90% of EGW (HPV 6 and 11). A close to 100 % efficacy&#xD;
      of the quadrivalent HPV vaccine (QHV) on prevention of EGW in naive patients has been shown,&#xD;
      leading to their near disappearance in the vaccinated population of countries with a good&#xD;
      vaccine coverage. Beside this preventive efficacy, literature data also show that HPV&#xD;
      vaccines have an up-to-100% protective effect versus recurrence of destroyed precancerous&#xD;
      lesions of the cervix in non-naive patients with an up-to-40 month's follow-up. Also, there&#xD;
      is anecdotal evidence that they could help treat severe wart conditions. QHV is also safe and&#xD;
      well tolerated when used in a preventive manner.&#xD;
&#xD;
      Investigator hypothesis is that QHV could have a protective effect on the recurrence of EGW&#xD;
      in patients who achieve complete remission.&#xD;
&#xD;
      The primary objective is to evaluate if the HPV vaccine, as compared to placebo, reduces the&#xD;
      relapse rate of external genital warts over a 12 month-period after their first injection.&#xD;
&#xD;
      The primary endpoint is the Relapse-free &quot;survival&quot;. Relapse will have to be clinically&#xD;
      confirmed.&#xD;
&#xD;
      The secondary objectives are : 1. To assess the improvement of the quality of life of the&#xD;
      patients 2. To investigate the clinical tolerance to three doses of HPV vaccine. The&#xD;
      secondary endpoints are&#xD;
&#xD;
        1. Disease relief score as evaluated by patients on a specific questionnaire for&#xD;
           Condylomata Acuminata (CECA) and Dermatology Life Quality Index (DLQI) self-administered&#xD;
           questionnaires over the treatment and follow-up periods&#xD;
&#xD;
        2. The clinical tolerance to HPV vaccine will be evaluated by assessment of the percentage&#xD;
           of patients with local and/or systemic reactions during the study&#xD;
&#xD;
      This is a National multicenter Phase III comparative, double blind randomized, two-parallel&#xD;
      groups clinical trial evaluating the efficacy of Gardasil vaccine versus placebo in EGW&#xD;
      population. Patients (300) recently cured of EGW will be enrolled over a 18 month-period and&#xD;
      will be randomized in a 1:1 ratio to receive three intra muscular (IM) vaccinations of either&#xD;
      Gardasil vaccine (150 subjects) or placebo (150 subjects) :&#xD;
&#xD;
        -  Group 1: Gardasil (at M0) + Gardasil (at M2) + Gardasil (at M6)&#xD;
&#xD;
        -  Group 2: Placebo (at M0) + Placebo (at M2) + Placebo (at M6) Subjects meeting all the&#xD;
           inclusion criteria and none of the exclusion criteria will be vaccinated by the&#xD;
           investigator or designee of the investigational center and will be examined by the&#xD;
           investigator or designee 30 minutes post immunization to assess for local and systemic&#xD;
           reactions.&#xD;
&#xD;
      All subjects will be followed by the investigators or designee during the study by phone&#xD;
      contacts and visits on site. Diary cards will be used after each vaccination to follow the&#xD;
      patients.&#xD;
&#xD;
      Number of visits /participant: 9 Schedule of visits : 1 selection visit (V0) , 3 vaccinations&#xD;
      scheduled on site at M0, M2 and M6, 3 phone contacts at M1, M3 and M7, 2 clinical follow up&#xD;
      visits on site at M9 and M12 + 1 unscheduled visit on site in case of EGW relapse during the&#xD;
      study&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 15, 2017</start_date>
  <completion_date type="Anticipated">April 2020</completion_date>
  <primary_completion_date type="Anticipated">March 2020</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>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Relapse free survival (days from first injection)</measure>
    <time_frame>up to 12 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Improvement of quality of life by Dermatology Life Quality Index (DLQI) validated scale</measure>
    <time_frame>at each planned visit/phone contact (1, 2, 3, 6, 7, 9 months), at 12 months (upon end of study visit) or upon premature withdrawal visit</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement of quality of life by CECA validated scale</measure>
    <time_frame>at each planned visit/phone contact (1, 2, 3, 6, 7, 9 months), at 12 months (upon end of study visit) or upon premature withdrawal visit</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical tolerance of QHV (percentage of patients with AE)</measure>
    <time_frame>Day 0</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical tolerance of QHV</measure>
    <time_frame>Month 2 and Month 6</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Genital Warts</condition>
  <arm_group>
    <arm_group_label>HPV Quadrivalent vaccine (QHV)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Gardasil</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Normal Saline</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Vaccination with Gardasil</intervention_name>
    <description>Vaccination with Gardasil in patients apparently cured of external genital warts</description>
    <arm_group_label>HPV Quadrivalent vaccine (QHV)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Injection of Normal Saline</intervention_name>
    <description>Injection of Normal Saline in patients apparently cured of external genital warts</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients aged 18 years and older;&#xD;
&#xD;
          -  Patients who, after the nature of the study has been explained to them, and prior to&#xD;
             any protocol specific procedures being performed, have given written consent according&#xD;
             to local regulatory requirements&#xD;
&#xD;
          -  Patients completely cured (no clinically visible lesions) for over two weeks and less&#xD;
             than a month prior to inclusion visit (V1, M0) after initial success of classic&#xD;
             treatment. If the patient has an EGW relapse, they will not be randomized and will be&#xD;
             considered as a screening failure. Screen-failed patients could perform another&#xD;
             selection visit after being completely cured (no clinically visible lesions).&#xD;
&#xD;
          -  Women of childbearing potential must have a negative pregnancy test and an effective&#xD;
             contraception from selection visit (V0) and up to the end of the vaccination period of&#xD;
             6 months;&#xD;
&#xD;
          -  Males must have an effective contraception with condoms from selection visit (V0) and&#xD;
             up to the end of the vaccination period of 6 months;&#xD;
&#xD;
          -  Patients affiliated to a social security regimen;&#xD;
&#xD;
          -  Patients able to participate during the 12 months of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with diagnosis of internal ano-genital warts (intra rectal, intra vaginal,&#xD;
             intra urethral) at the selection visit&#xD;
&#xD;
          -  Patients with positive HIV, Hepatitis C virus (HCV) or Hepatitis B virus (HBV) (Ag&#xD;
             HBS) tests;&#xD;
&#xD;
          -  Patients whose regular partner(s) have active uncontrolled clinical EGW;&#xD;
&#xD;
          -  Patients who received the HPV Vaccine at any time before enrolment to the study;&#xD;
&#xD;
          -  Any serious chronic or progressive disease according to the judgement of the&#xD;
             investigator;&#xD;
&#xD;
          -  Patients with history of an autoimmune disorder or any other known or suspected&#xD;
             impairment /alteration of the immune system, or under immunosuppressive therapy&#xD;
             including use of systemic corticosteroids or chronic immunosuppressant medication&#xD;
             (more than 14 days) (i.e. prednisone, or equivalent ≥10 mg/day) within :&#xD;
&#xD;
               -  the 28 days preceding the first vaccination at the inclusion visit V1 in case of&#xD;
                  corticosteroids administration&#xD;
&#xD;
               -  the 3 months preceding the first vaccination at the inclusion visit V1 in case of&#xD;
                  administration of cyclophosphamide, anti-Tumor Necrosis Factor (TNF) alpha ,&#xD;
                  intravenous immunoglobulins, abatacept, corticosteroids as a bolus injection&#xD;
&#xD;
               -  the 6 months preceding the first vaccination at the inclusion visit V1 in case of&#xD;
                  Cluster of Differentiation antigen 20 (anti-CD20) administration. Topical or&#xD;
                  inhaled uses of steroid including intranasal are allowed;&#xD;
&#xD;
          -  Patients with history of known allergies/hypersensitivity to any component of study&#xD;
             vaccine;&#xD;
&#xD;
          -  Patients who have any malignancy or lymphoproliferative disorder;&#xD;
&#xD;
          -  Patients with thrombocytopenia or coagulation disorder/treatment contra-indicating&#xD;
             intramuscular injection;&#xD;
&#xD;
          -  Women who are pregnant or are breast-feeding, or are of childbearing age who do not&#xD;
             use or do not plan to use acceptable birth control measures, during the first 6 months&#xD;
             of the study ;&#xD;
&#xD;
          -  Male who do not use or do not plan to use condoms during the first 6 months of the&#xD;
             study;&#xD;
&#xD;
          -  Patients under a measure of legal protection or unable to consent;&#xD;
&#xD;
          -  Patients participating in any clinical trial with another investigational product 28&#xD;
             days prior to first study visit or intent to participate in another clinical study at&#xD;
             any time during the conduct of this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sebastien FOUERE, MD, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sebastien FOUERE, MD, MSc</last_name>
    <phone>(0)1 42 49 99 24</phone>
    <phone_ext>+33</phone_ext>
    <email>sebastien.fouere@aphp.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Olivier CHOSIDOW, MD, PhD</last_name>
    <phone>(0)1 49 81 25 01</phone>
    <phone_ext>+33</phone_ext>
    <email>olivier.chosidow@aphp.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hôpital St Louis</name>
      <address>
        <city>Paris</city>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sebastien FOUERE, MD, MSc</last_name>
      <phone>(0)1 42 49 99 24</phone>
      <email>sebastien.fouere@aphp.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>GH Cochin - Broca - Hôtel-Dieu,</name>
      <address>
        <city>Paris</city>
        <zip>75679</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Odile LAUNAY, PH</last_name>
      <phone>(0)1 58 41 28 58</phone>
      <phone_ext>+33</phone_ext>
      <email>odile.launay@aphp.fr</email>
    </contact>
    <contact_backup>
      <last_name>Laurence MOULAY</last_name>
      <phone>(0)1 58 41 24 51</phone>
      <phone_ext>+33</phone_ext>
      <email>laurence.moulay@aphp.fr</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>July 24, 2017</study_first_submitted>
  <study_first_submitted_qc>September 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 28, 2017</study_first_posted>
  <last_update_submitted>February 26, 2018</last_update_submitted>
  <last_update_submitted_qc>February 26, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 27, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Genital warts</keyword>
  <keyword>HPV vaccine</keyword>
  <keyword>Relapse</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Warts</mesh_term>
    <mesh_term>Condylomata Acuminata</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03296397
org study id: P150957
nct id: NCT03296397
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
External genital warts (EGW) are a frequent disease (typical yearly incidence of 100 to 200
      new cases per 100.000 person-years, typical prevalence of 1 to 4% of the sexually active
      population), with a heavy toll on patients' quality of life: low self-esteem and severe
      impairment of sexual well-being are common consequences. Treatments are painful and take time
      to achieve cure because of low complete remission (20 to 60%) and high recurrence rates (10
      to 40%, 30% on average). Finding new means to reduce these recurrence rates thus seems
      justified. Infection with Human Papillomavirus (HPV) is responsible for EGW,other warts and
      some epithelial cancers. Out of two currently available HPV vaccines (Cervarix and
      Gardasil®), only Gardasil® is " quadrivalent " i.e. contains virus like particles imparting
      protection versus 4 genotypes of HPV, 2 of them responsible of most cancers and pre cancers
      of the cervix (HPV 16 and 18), and 2 for 90% of EGW (HPV 6 and 11). A close to 100 % efficacy
      of the quadrivalent HPV vaccine (QHV) on prevention of EGW in naive patients has been shown,
      leading to their near disappearance in the vaccinated population of countries with a good
      vaccine coverage. Beside this preventive efficacy, literature data also show that HPV
      vaccines have an up-to-100% protective effect versus recurrence of destroyed precancerous
      lesions of the cervix in non-naive patients with an up-to-40 month's follow-up. Also, there
      is anecdotal evidence that they could help treat severe wart conditions. QHV is also safe and
      well tolerated when used in a preventive manner.

      Investigator hypothesis is that QHV could have a protective effect on the recurrence of EGW
      in patients who achieve complete remission.

      The primary objective is to evaluate if the HPV vaccine, as compared to placebo, reduces the
      relapse rate of external genital warts over a 12 month-period after their first injection.

      The primary endpoint is the Relapse-free "survival". Relapse will have to be clinically
      confirmed.

      The secondary objectives are : 1. To assess the improvement of the quality of life of the
      patients 2. To investigate the clinical tolerance to three doses of HPV vaccine. The
      secondary endpoints are

        1. Disease relief score as evaluated by patients on a specific questionnaire for
           Condylomata Acuminata (CECA) and Dermatology Life Quality Index (DLQI) self-administered
           questionnaires over the treatment and follow-up periods

        2. The clinical tolerance to HPV vaccine will be evaluated by assessment of the percentage
           of patients with local and/or systemic reactions during the study

      This is a National multicenter Phase III comparative, double blind randomized, two-parallel
      groups clinical trial evaluating the efficacy of Gardasil vaccine versus placebo in EGW
      population. Patients (300) recently cured of EGW will be enrolled over a 18 month-period and
      will be randomized in a 1:1 ratio to receive three intra muscular (IM) vaccinations of either
      Gardasil vaccine (150 subjects) or placebo (150 subjects) :

        -  Group 1: Gardasil (at M0) + Gardasil (at M2) + Gardasil (at M6)

        -  Group 2: Placebo (at M0) + Placebo (at M2) + Placebo (at M6) Subjects meeting all the
           inclusion criteria and none of the exclusion criteria will be vaccinated by the
           investigator or designee of the investigational center and will be examined by the
           investigator or designee 30 minutes post immunization to assess for local and systemic
           reactions.

      All subjects will be followed by the investigators or designee during the study by phone
      contacts and visits on site. Diary cards will be used after each vaccination to follow the
      patients.

      Number of visits /participant: 9 Schedule of visits : 1 selection visit (V0) , 3 vaccinations
      scheduled on site at M0, M2 and M6, 3 phone contacts at M1, M3 and M7, 2 clinical follow up
      visits on site at M9 and M12 + 1 unscheduled visit on site in case of EGW relapse during the
      study
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Relapse free survival (days from first injection)
time frame: up to 12 months
measure: Improvement of quality of life by Dermatology Life Quality Index (DLQI) validated scale
time frame: at each planned visit/phone contact (1, 2, 3, 6, 7, 9 months), at 12 months (upon end of study visit) or upon premature withdrawal visit
measure: Improvement of quality of life by CECA validated scale
time frame: at each planned visit/phone contact (1, 2, 3, 6, 7, 9 months), at 12 months (upon end of study visit) or upon premature withdrawal visit
measure: Clinical tolerance of QHV (percentage of patients with AE)
time frame: Day 0
measure: Clinical tolerance of QHV
time frame: Month 2 and Month 6
arm group label: HPV Quadrivalent vaccine (QHV)
arm group type: Active Comparator
description: Gardasil
arm group label: Placebo
arm group type: Placebo Comparator
description: Normal Saline
intervention type: Biological
intervention name: Vaccination with Gardasil
description: Vaccination with Gardasil in patients apparently cured of external genital warts
arm group label: HPV Quadrivalent vaccine (QHV)
intervention type: Biological
intervention name: Injection of Normal Saline
description: Injection of Normal Saline in patients apparently cured of external genital warts
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sebastien FOUERE, MD, MSc
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
last name: Sebastien FOUERE, MD, MSc
phone: (0)1 42 49 99 24
phone ext: +33
email: sebastien.fouere@aphp.fr
last name: Olivier CHOSIDOW, MD, PhD
phone: (0)1 49 81 25 01
phone ext: +33
email: olivier.chosidow@aphp.fr
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
contact backup: 
country: France
responsible party type: Sponsor
mesh term: Warts
mesh term: Condylomata Acuminata
sharing ipd: Undecided