<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/NCT01687192</url>
  </required_header>
  <id_info>
    <org_study_id>CHUBX 2011/18</org_study_id>
    <nct_id>NCT01687192</nct_id>
  </id_info>
  <brief_title>Multicenter Trial Evaluating the Immunogenicity of HPV Vaccination in Girls on Immunosuppressive Therapy.</brief_title>
  <acronym>PRIMAVERA</acronym>
  <official_title>Multicenter Clinical Trial Evaluating the Immunological Response of Vaccination Against Infection by Human Papillomavirus (HPV) 6, 11, 16, 18 in Girls Receiving Immunosuppressive Therapy.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Bordeaux</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Bordeaux</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      PRIMAVERA is a Phase IIa clinical trial, with the objective to assess the immunologic&#xD;
      response to HPV vaccine in a population of immunocompromised girls. The principal hypothesis&#xD;
      is that the immunologic response to tetravalent vaccine in girls who received&#xD;
      immunosuppressive treatment is comparable to the immunologic response in girls that are not&#xD;
      immunosuppressed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The human papillomaviruses (HPV) are the cause of the most common sexually transmitted&#xD;
      infection. Among oncogenic HPV, HPV 16 and 18 are found in 70% of invasive cancers. Among the&#xD;
      non-oncogenic HPV, HPV 6 and 11 are found in 90% of anogenital warts. Two prophylactic&#xD;
      vaccines are currently available: Gardasil ® protects against HPV 6, 11, 16 and 18 and&#xD;
      Cervarix ® that protects against HPV16 and 18. Gardasil ® is indicated for the prevention of&#xD;
      high-grade cervical dysplasia (CIN2-3), cancers of the cervix, high-grade dysplasia of the&#xD;
      vulva (VIN2-3) and genital warts.&#xD;
&#xD;
      The choice of Gardasil ® is linked to the theoretical risk of graft rejection with the&#xD;
      bivalent vaccine, and the fact that the frequency of anogenital warts related to HPV 6 and 11&#xD;
      is increased in the immunocompromised population.&#xD;
&#xD;
      The immunosuppressed women are more likely to present abnormal cervical smears than general&#xD;
      population.&#xD;
&#xD;
      A notice on the age of vaccination against HPV for girls to receive a transplant was made by&#xD;
      the High Council of Public Health, recommending that vaccination against HPV could be offered&#xD;
      to girls to benefit a transplant before the age of 14 years and according to data from the&#xD;
      MA. The High Council of Public Health also renewed its request that studies be conducted&#xD;
      specifically on the vaccination of girls and young women, immunocompromised, including those&#xD;
      receiving immunosuppressive therapy.&#xD;
&#xD;
      The primary objective is to evaluate the persistence of immunological response to tetravalent&#xD;
      HPV vaccine at 18 months after first dose of vaccine.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>October 2012</start_date>
  <completion_date type="Anticipated">November 2016</completion_date>
  <primary_completion_date type="Actual">May 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Seroconversion rate for HPV 16 and 18 at M18</measure>
    <time_frame>18 months after first dose of vacinne (i.e. Inclusion visit)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Geometric means of anti-HPV 6, 11, 16 and 18 antibody titers at M7, M18, and M36, respectively.</measure>
    <time_frame>Samples collected 7, 18 and 36 months after first dose of vaccine</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with a good cell response at M7 and M18</measure>
    <time_frame>7 and 18 months after first dose of vaccine</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with genital warts or cervical lesions (if relevant)</measure>
    <time_frame>36 months after first dose of vaccine</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number, type and time of occurrence of adverse events of any grade during 18 months after first dose of vaccine</measure>
    <time_frame>Assessed at months 2,6,7 and 18 after first dose of vaccine</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">37</enrollment>
  <condition>Transplantation</condition>
  <condition>Systemic Lupus Erythematosus</condition>
  <condition>Systemic Immune Disease</condition>
  <arm_group>
    <arm_group_label>Girls and young womens receiving immunosuppressive treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>HPV prophylactic vaccine Gardasil</intervention_name>
    <description>3 injections: at Inclusion visit then 2 and 6 months after.</description>
    <arm_group_label>Girls and young womens receiving immunosuppressive treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female gender&#xD;
&#xD;
          -  Age ≥ 9 years and &lt; 18 years&#xD;
&#xD;
          -  Weight ≥ 25 kg&#xD;
&#xD;
          -  Solid organ transplantation: kidney, liver, heart, lung, intestinal or combined&#xD;
             transplant; or systemic lupus erythematosus or other systemic immune disease&#xD;
&#xD;
          -  Transplantation or diagnosis of lupus or diagnosis of systemic immune disease since&#xD;
             more than 6 months&#xD;
&#xD;
          -  Immunosuppressant treatment by anti-metabolites or calcineurin inhibitors, with or&#xD;
             without associated corticosteroids&#xD;
&#xD;
          -  Minimum required period of 3 months considered as stable after transplantation or&#xD;
             without relapse of lupus according to physician evaluation&#xD;
&#xD;
          -  In case of sexual activity (assessed by auto-declaration): onset less than one year&#xD;
             before inclusion&#xD;
&#xD;
          -  Written informed consent signed by the investigator and the legal representatives of&#xD;
             the patient, and assent by the patient&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Male gender&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Age &lt; 9 years or ≥ 18 years&#xD;
&#xD;
          -  Previous HPV vaccination&#xD;
&#xD;
          -  Immunosuppressive treatment by anti-TNF (adalimumab, etanercept, infliximab) or&#xD;
             monoclonal antibodies (rituximab, anakinra, abatacept) during the last 3 months&#xD;
&#xD;
          -  Active malignancy&#xD;
&#xD;
          -  Active opportunistic infection&#xD;
&#xD;
          -  HIV infection&#xD;
&#xD;
          -  Concurrent clinical trial&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>9 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Geneviève CHENE, MD-PhD</last_name>
    <role>Study Chair</role>
    <affiliation>University Hospital, Bordeaux, USMR</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jerome HARAMBAT, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Bordeaux</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU de Bordeaux, Hôpital Pellegrin-Enfants</name>
      <address>
        <city>Bordeaux</city>
        <zip>33076</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HCLyon, Hôpital Femme-mère-enfant</name>
      <address>
        <city>Bron</city>
        <zip>69677</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Lille, Hôpital Jeanne de Flandres</name>
      <address>
        <city>Lille</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Montpellier, Hôpital Arnaud de Villeneuve</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Nantes, Hôpital Mère-Enfants</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AP-HP, Hôpital Robert Debré</name>
      <address>
        <city>Paris</city>
        <zip>75019</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AP-HP, Hôpital Armand Trousseau</name>
      <address>
        <city>Paris</city>
        <zip>75571</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AP-HP, Hôpital Necker-Enfants</name>
      <address>
        <city>Paris</city>
        <zip>75743</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Toulouse, Hôpital des Enfants</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Koutsky L. The epidemiology behind the HPV vaccine discovery. Ann Epidemiol. 2009 Apr;19(4):239-44. doi: 10.1016/j.annepidem.2009.01.023.</citation>
    <PMID>19344861</PMID>
  </reference>
  <reference>
    <citation>Johnson AM, Mercer CH, Erens B, Copas AJ, McManus S, Wellings K, Fenton KA, Korovessis C, Macdowall W, Nanchahal K, Purdon S, Field J. Sexual behaviour in Britain: partnerships, practices, and HIV risk behaviours. Lancet. 2001 Dec 1;358(9296):1835-42. doi: 10.1016/S0140-6736(01)06883-0.</citation>
    <PMID>11741621</PMID>
  </reference>
  <reference>
    <citation>Winer RL, Lee SK, Hughes JP, Adam DE, Kiviat NB, Koutsky LA. Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol. 2003 Feb 1;157(3):218-26. doi: 10.1093/aje/kwf180. Erratum In: Am J Epidemiol. 2003 May 1;157(9):858.</citation>
    <PMID>12543621</PMID>
  </reference>
  <reference>
    <citation>Collins S, Mazloomzadeh S, Winter H, Blomfield P, Bailey A, Young LS, Woodman CB. High incidence of cervical human papillomavirus infection in women during their first sexual relationship. BJOG. 2002 Jan;109(1):96-8. doi: 10.1111/j.1471-0528.2002.01053.x.</citation>
    <PMID>11845815</PMID>
  </reference>
  <reference>
    <citation>Myers ER, McCrory DC, Nanda K, Bastian L, Matchar DB. Mathematical model for the natural history of human papillomavirus infection and cervical carcinogenesis. Am J Epidemiol. 2000 Jun 15;151(12):1158-71. doi: 10.1093/oxfordjournals.aje.a010166.</citation>
    <PMID>10905528</PMID>
  </reference>
  <reference>
    <citation>Penn I. Occurrence of cancers in immunosuppressed organ transplant recipients. Clin Transpl. 1998:147-58.</citation>
    <PMID>10503093</PMID>
  </reference>
  <reference>
    <citation>Fairley CK, Chen S, Tabrizi SN, McNeil J, Becker G, Walker R, Atkins RC, Thomson N, Allan P, Woodburn C, et al. Prevalence of HPV DNA in cervical specimens in women with renal transplants: a comparison with dialysis-dependent patients and patients with renal impairment. Nephrol Dial Transplant. 1994;9(4):416-20.</citation>
    <PMID>8084456</PMID>
  </reference>
  <reference>
    <citation>ter Haar-van Eck SA, Rischen-Vos J, Chadha-Ajwani S, Huikeshoven FJ. The incidence of cervical intraepithelial neoplasia among women with renal transplant in relation to cyclosporine. Br J Obstet Gynaecol. 1995 Jan;102(1):58-61. doi: 10.1111/j.1471-0528.1995.tb09027.x.</citation>
    <PMID>7833312</PMID>
  </reference>
  <reference>
    <citation>Fairley CK, Sheil AG, McNeil JJ, Ugoni AM, Disney AP, Giles GG, Amiss N. The risk of ano-genital malignancies in dialysis and transplant patients. Clin Nephrol. 1994 Feb;41(2):101-5.</citation>
    <PMID>8004825</PMID>
  </reference>
  <reference>
    <citation>Kessler M, Jay N, Molle R, Guillemin F. Excess risk of cancer in renal transplant patients. Transpl Int. 2006 Nov;19(11):908-14. doi: 10.1111/j.1432-2277.2006.00383.x.</citation>
    <PMID>17018126</PMID>
  </reference>
  <reference>
    <citation>Birkeland SA, Lokkegaard H, Storm HH. Cancer risk in patients on dialysis and after renal transplantation. Lancet. 2000 May 27;355(9218):1886-7. doi: 10.1016/s0140-6736(00)02298-4.</citation>
    <PMID>10866449</PMID>
  </reference>
  <reference>
    <citation>Vajdic CM, McDonald SP, McCredie MR, van Leeuwen MT, Stewart JH, Law M, Chapman JR, Webster AC, Kaldor JM, Grulich AE. Cancer incidence before and after kidney transplantation. JAMA. 2006 Dec 20;296(23):2823-31. doi: 10.1001/jama.296.23.2823.</citation>
    <PMID>17179459</PMID>
  </reference>
  <reference>
    <citation>Nyberg G, Eriksson O, Westberg NG. Increased incidence of cervical atypia in women with systemic lupus erythematosus treated with chemotherapy. Arthritis Rheum. 1981 May;24(5):648-50. doi: 10.1002/art.1780240503.</citation>
    <PMID>7236321</PMID>
  </reference>
  <reference>
    <citation>Nath R, Mant C, Luxton J, Hughes G, Raju KS, Shepherd P, Cason J. High risk of human papillomavirus type 16 infections and of development of cervical squamous intraepithelial lesions in systemic lupus erythematosus patients. Arthritis Rheum. 2007 May 15;57(4):619-25. doi: 10.1002/art.22667.</citation>
    <PMID>17471531</PMID>
  </reference>
  <reference>
    <citation>Tam LS, Chan PK, Ho SC, Yu MM, Yim SF, Cheung TH, Wong MC, Li EK. Natural history of cervical papilloma virus infection in systemic lupus erythematosus - a prospective cohort study. J Rheumatol. 2010 Feb;37(2):330-40. doi: 10.3899/jrheum.090644. Epub 2009 Dec 23.</citation>
    <PMID>20032093</PMID>
  </reference>
  <reference>
    <citation>Kirnbauer R, Hubbert NL, Wheeler CM, Becker TM, Lowy DR, Schiller JT. A virus-like particle enzyme-linked immunosorbent assay detects serum antibodies in a majority of women infected with human papillomavirus type 16. J Natl Cancer Inst. 1994 Apr 6;86(7):494-9. doi: 10.1093/jnci/86.7.494.</citation>
    <PMID>8133532</PMID>
  </reference>
  <reference>
    <citation>Joura EA, Kjaer SK, Wheeler CM, Sigurdsson K, Iversen OE, Hernandez-Avila M, Perez G, Brown DR, Koutsky LA, Tay EH, Garcia P, Ault KA, Garland SM, Leodolter S, Olsson SE, Tang GW, Ferris DG, Paavonen J, Lehtinen M, Steben M, Bosch X, Dillner J, Kurman RJ, Majewski S, Munoz N, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan J, Lupinacci LC, Giacoletti KE, Lu S, Vuocolo S, Hesley TM, Haupt RM, Barr E. HPV antibody levels and clinical efficacy following administration of a prophylactic quadrivalent HPV vaccine. Vaccine. 2008 Dec 9;26(52):6844-51. doi: 10.1016/j.vaccine.2008.09.073. Epub 2008 Oct 16.</citation>
    <PMID>18930097</PMID>
  </reference>
  <reference>
    <citation>Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S, Tang GW, Ferris DG, Steben M, Bryan J, Taddeo FJ, Railkar R, Esser MT, Sings HL, Nelson M, Boslego J, Sattler C, Barr E, Koutsky LA; Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE) I Investigators. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med. 2007 May 10;356(19):1928-43. doi: 10.1056/NEJMoa061760.</citation>
    <PMID>17494926</PMID>
  </reference>
  <reference>
    <citation>FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007 May 10;356(19):1915-27. doi: 10.1056/NEJMoa061741.</citation>
    <PMID>17494925</PMID>
  </reference>
  <reference>
    <citation>Mao C, Koutsky LA, Ault KA, Wheeler CM, Brown DR, Wiley DJ, Alvarez FB, Bautista OM, Jansen KU, Barr E. Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia: a randomized controlled trial. Obstet Gynecol. 2006 Jan;107(1):18-27. doi: 10.1097/01.AOG.0000192397.41191.fb. Erratum In: Obstet Gynecol. 2006 Jun;107(6):1425.</citation>
    <PMID>16394035</PMID>
  </reference>
  <reference>
    <citation>Villa LL, Costa RL, Petta CA, Andrade RP, Ault KA, Giuliano AR, Wheeler CM, Koutsky LA, Malm C, Lehtinen M, Skjeldestad FE, Olsson SE, Steinwall M, Brown DR, Kurman RJ, Ronnett BM, Stoler MH, Ferenczy A, Harper DM, Tamms GM, Yu J, Lupinacci L, Railkar R, Taddeo FJ, Jansen KU, Esser MT, Sings HL, Saah AJ, Barr E. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol. 2005 May;6(5):271-8. doi: 10.1016/S1470-2045(05)70101-7.</citation>
    <PMID>15863374</PMID>
  </reference>
  <reference>
    <citation>Ault KA; Future II Study Group. Effect of prophylactic human papillomavirus L1 virus-like-particle vaccine on risk of cervical intraepithelial neoplasia grade 2, grade 3, and adenocarcinoma in situ: a combined analysis of four randomised clinical trials. Lancet. 2007 Jun 2;369(9576):1861-1868. doi: 10.1016/S0140-6736(07)60852-6.</citation>
    <PMID>17544766</PMID>
  </reference>
  <reference>
    <citation>Joura EA, Leodolter S, Hernandez-Avila M, Wheeler CM, Perez G, Koutsky LA, Garland SM, Harper DM, Tang GW, Ferris DG, Steben M, Jones RW, Bryan J, Taddeo FJ, Bautista OM, Esser MT, Sings HL, Nelson M, Boslego JW, Sattler C, Barr E, Paavonen J. Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of three randomised clinical trials. Lancet. 2007 May 19;369(9574):1693-702. doi: 10.1016/S0140-6736(07)60777-6.</citation>
    <PMID>17512854</PMID>
  </reference>
  <reference>
    <citation>Hildesheim A, Herrero R, Wacholder S, Rodriguez AC, Solomon D, Bratti MC, Schiller JT, Gonzalez P, Dubin G, Porras C, Jimenez SE, Lowy DR; Costa Rican HPV Vaccine Trial Group. Effect of human papillomavirus 16/18 L1 viruslike particle vaccine among young women with preexisting infection: a randomized trial. JAMA. 2007 Aug 15;298(7):743-53. doi: 10.1001/jama.298.7.743.</citation>
    <PMID>17699008</PMID>
  </reference>
  <reference>
    <citation>Slade BA, Leidel L, Vellozzi C, Woo EJ, Hua W, Sutherland A, Izurieta HS, Ball R, Miller N, Braun MM, Markowitz LE, Iskander J. Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine. JAMA. 2009 Aug 19;302(7):750-7. doi: 10.1001/jama.2009.1201.</citation>
    <PMID>19690307</PMID>
  </reference>
  <reference>
    <citation>Villa LL, Costa RL, Petta CA, Andrade RP, Paavonen J, Iversen OE, Olsson SE, Hoye J, Steinwall M, Riis-Johannessen G, Andersson-Ellstrom A, Elfgren K, Krogh Gv, Lehtinen M, Malm C, Tamms GM, Giacoletti K, Lupinacci L, Railkar R, Taddeo FJ, Bryan J, Esser MT, Sings HL, Saah AJ, Barr E. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer. 2006 Dec 4;95(11):1459-66. doi: 10.1038/sj.bjc.6603469. Epub 2006 Nov 21.</citation>
    <PMID>17117182</PMID>
  </reference>
  <reference>
    <citation>Olsson SE, Villa LL, Costa RL, Petta CA, Andrade RP, Malm C, Iversen OE, Hoye J, Steinwall M, Riis-Johannessen G, Andersson-Ellstrom A, Elfgren K, von Krogh G, Lehtinen M, Paavonen J, Tamms GM, Giacoletti K, Lupinacci L, Esser MT, Vuocolo SC, Saah AJ, Barr E. Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine. Vaccine. 2007 Jun 21;25(26):4931-9. doi: 10.1016/j.vaccine.2007.03.049. Epub 2007 Apr 20.</citation>
    <PMID>17499406</PMID>
  </reference>
  <reference>
    <citation>Reisinger KS, Block SL, Lazcano-Ponce E, Samakoses R, Esser MT, Erick J, Puchalski D, Giacoletti KE, Sings HL, Lukac S, Alvarez FB, Barr E. Safety and persistent immunogenicity of a quadrivalent human papillomavirus types 6, 11, 16, 18 L1 virus-like particle vaccine in preadolescents and adolescents: a randomized controlled trial. Pediatr Infect Dis J. 2007 Mar;26(3):201-9. doi: 10.1097/01.inf.0000253970.29190.5a.</citation>
    <PMID>17484215</PMID>
  </reference>
  <reference>
    <citation>Levin MJ, Moscicki AB, Song LY, Fenton T, Meyer WA 3rd, Read JS, Handelsman EL, Nowak B, Sattler CA, Saah A, Radley DR, Esser MT, Weinberg A; IMPAACT P1047 Protocol Team. Safety and immunogenicity of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine in HIV-infected children 7 to 12 years old. J Acquir Immune Defic Syndr. 2010 Oct;55(2):197-204. doi: 10.1097/QAI.0b013e3181de8d26.</citation>
    <PMID>20574412</PMID>
  </reference>
  <reference>
    <citation>Grabowska K, Wang X, Jacobsson A, Dillner J. Evaluation of cost-precision rations of different strategies for ELISA measurement of serum antibody levels. J Immunol Methods. 2002 Dec 20;271(1-2):1-15. doi: 10.1016/s0022-1759(02)00334-4.</citation>
    <PMID>12445724</PMID>
  </reference>
  <reference>
    <citation>Dessy FJ, Giannini SL, Bougelet CA, Kemp TJ, David MP, Poncelet SM, Pinto LA, Wettendorff MA. Correlation between direct ELISA, single epitope-based inhibition ELISA and pseudovirion-based neutralization assay for measuring anti-HPV-16 and anti-HPV-18 antibody response after vaccination with the AS04-adjuvanted HPV-16/18 cervical cancer vaccine. Hum Vaccin. 2008 Nov-Dec;4(6):425-34. doi: 10.4161/hv.4.6.6912. Epub 2008 Nov 11.</citation>
    <PMID>18948732</PMID>
  </reference>
  <reference>
    <citation>Waterboer T, Sehr P, Michael KM, Franceschi S, Nieland JD, Joos TO, Templin MF, Pawlita M. Multiplex human papillomavirus serology based on in situ-purified glutathione s-transferase fusion proteins. Clin Chem. 2005 Oct;51(10):1845-53. doi: 10.1373/clinchem.2005.052381. Epub 2005 Aug 11.</citation>
    <PMID>16099939</PMID>
  </reference>
  <reference>
    <citation>Michael KM, Waterboer T, Sehr P, Rother A, Reidel U, Boeing H, Bravo IG, Schlehofer J, Gartner BC, Pawlita M. Seroprevalence of 34 human papillomavirus types in the German general population. PLoS Pathog. 2008 Jun 20;4(6):e1000091. doi: 10.1371/journal.ppat.1000091.</citation>
    <PMID>18566657</PMID>
  </reference>
  <reference>
    <citation>Mendez F, Munoz N, Posso H, Molano M, Moreno V, van den Brule AJ, Ronderos M, Meijer C, Munoz A; Instituto Nacional de Cancerologia Human Papillomavirus Study Group. Cervical coinfection with human papillomavirus (HPV) types and possible implications for the prevention of cervical cancer by HPV vaccines. J Infect Dis. 2005 Oct 1;192(7):1158-65. doi: 10.1086/444391. Epub 2005 Aug 29.</citation>
    <PMID>16136457</PMID>
  </reference>
  <verification_date>July 2015</verification_date>
  <study_first_submitted>September 13, 2012</study_first_submitted>
  <study_first_submitted_qc>September 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 18, 2012</study_first_posted>
  <last_update_submitted>July 30, 2015</last_update_submitted>
  <last_update_submitted_qc>July 30, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 31, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Seroconversion</keyword>
  <keyword>Immunosuppressed treatment</keyword>
  <keyword>HPV vaccination</keyword>
  <keyword>Immunogenicity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lupus Erythematosus, Systemic</mesh_term>
    <mesh_term>Immune System Diseases</mesh_term>
  </condition_browse>
  <!-- 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/NCT01687192
org study id: CHUBX 2011/18
nct id: NCT01687192
lead sponsor: 
has dmc: No
PRIMAVERA is a Phase IIa clinical trial, with the objective to assess the immunologic
      response to HPV vaccine in a population of immunocompromised girls. The principal hypothesis
      is that the immunologic response to tetravalent vaccine in girls who received
      immunosuppressive treatment is comparable to the immunologic response in girls that are not
      immunosuppressed.
The human papillomaviruses (HPV) are the cause of the most common sexually transmitted
      infection. Among oncogenic HPV, HPV 16 and 18 are found in 70% of invasive cancers. Among the
      non-oncogenic HPV, HPV 6 and 11 are found in 90% of anogenital warts. Two prophylactic
      vaccines are currently available: Gardasil ® protects against HPV 6, 11, 16 and 18 and
      Cervarix ® that protects against HPV16 and 18. Gardasil ® is indicated for the prevention of
      high-grade cervical dysplasia (CIN2-3), cancers of the cervix, high-grade dysplasia of the
      vulva (VIN2-3) and genital warts.

      The choice of Gardasil ® is linked to the theoretical risk of graft rejection with the
      bivalent vaccine, and the fact that the frequency of anogenital warts related to HPV 6 and 11
      is increased in the immunocompromised population.

      The immunosuppressed women are more likely to present abnormal cervical smears than general
      population.

      A notice on the age of vaccination against HPV for girls to receive a transplant was made by
      the High Council of Public Health, recommending that vaccination against HPV could be offered
      to girls to benefit a transplant before the age of 14 years and according to data from the
      MA. The High Council of Public Health also renewed its request that studies be conducted
      specifically on the vaccination of girls and young women, immunocompromised, including those
      receiving immunosuppressive therapy.

      The primary objective is to evaluate the persistence of immunological response to tetravalent
      HPV vaccine at 18 months after first dose of vaccine.
allocation: Non-Randomized
intervention model: Single Group Assignment
masking: None (Open Label)
measure: Seroconversion rate for HPV 16 and 18 at M18
time frame: 18 months after first dose of vacinne (i.e. Inclusion visit)
measure: Geometric means of anti-HPV 6, 11, 16 and 18 antibody titers at M7, M18, and M36, respectively.
time frame: Samples collected 7, 18 and 36 months after first dose of vaccine
measure: Proportion of patients with a good cell response at M7 and M18
time frame: 7 and 18 months after first dose of vaccine
measure: Proportion of patients with genital warts or cervical lesions (if relevant)
time frame: 36 months after first dose of vaccine
measure: Number, type and time of occurrence of adverse events of any grade during 18 months after first dose of vaccine
time frame: Assessed at months 2,6,7 and 18 after first dose of vaccine
arm group label: Girls and young womens receiving immunosuppressive treatment
arm group type: Experimental
intervention type: Biological
intervention name: HPV prophylactic vaccine Gardasil
description: 3 injections: at Inclusion visit then 2 and 6 months after.
arm group label: Girls and young womens receiving immunosuppressive treatment
criteria: 
gender: Female
minimum age: 9 Years
maximum age: 18 Years
healthy volunteers: No
last name: Geneviève CHENE, MD-PhD
role: Study Chair
affiliation: University Hospital, Bordeaux, USMR
last name: Jerome HARAMBAT, MD
role: Principal Investigator
affiliation: University Hospital, Bordeaux
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
citation: Koutsky L. The epidemiology behind the HPV vaccine discovery. Ann Epidemiol. 2009 Apr;19(4):239-44. doi: 10.1016/j.annepidem.2009.01.023.
PMID: 19344861
citation: Johnson AM, Mercer CH, Erens B, Copas AJ, McManus S, Wellings K, Fenton KA, Korovessis C, Macdowall W, Nanchahal K, Purdon S, Field J. Sexual behaviour in Britain: partnerships, practices, and HIV risk behaviours. Lancet. 2001 Dec 1;358(9296):1835-42. doi: 10.1016/S0140-6736(01)06883-0.
PMID: 11741621
citation: Winer RL, Lee SK, Hughes JP, Adam DE, Kiviat NB, Koutsky LA. Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol. 2003 Feb 1;157(3):218-26. doi: 10.1093/aje/kwf180. Erratum In: Am J Epidemiol. 2003 May 1;157(9):858.
PMID: 12543621
citation: Collins S, Mazloomzadeh S, Winter H, Blomfield P, Bailey A, Young LS, Woodman CB. High incidence of cervical human papillomavirus infection in women during their first sexual relationship. BJOG. 2002 Jan;109(1):96-8. doi: 10.1111/j.1471-0528.2002.01053.x.
PMID: 11845815
citation: Myers ER, McCrory DC, Nanda K, Bastian L, Matchar DB. Mathematical model for the natural history of human papillomavirus infection and cervical carcinogenesis. Am J Epidemiol. 2000 Jun 15;151(12):1158-71. doi: 10.1093/oxfordjournals.aje.a010166.
PMID: 10905528
citation: Penn I. Occurrence of cancers in immunosuppressed organ transplant recipients. Clin Transpl. 1998:147-58.
PMID: 10503093
citation: Fairley CK, Chen S, Tabrizi SN, McNeil J, Becker G, Walker R, Atkins RC, Thomson N, Allan P, Woodburn C, et al. Prevalence of HPV DNA in cervical specimens in women with renal transplants: a comparison with dialysis-dependent patients and patients with renal impairment. Nephrol Dial Transplant. 1994;9(4):416-20.
PMID: 8084456
citation: ter Haar-van Eck SA, Rischen-Vos J, Chadha-Ajwani S, Huikeshoven FJ. The incidence of cervical intraepithelial neoplasia among women with renal transplant in relation to cyclosporine. Br J Obstet Gynaecol. 1995 Jan;102(1):58-61. doi: 10.1111/j.1471-0528.1995.tb09027.x.
PMID: 7833312
citation: Fairley CK, Sheil AG, McNeil JJ, Ugoni AM, Disney AP, Giles GG, Amiss N. The risk of ano-genital malignancies in dialysis and transplant patients. Clin Nephrol. 1994 Feb;41(2):101-5.
PMID: 8004825
citation: Kessler M, Jay N, Molle R, Guillemin F. Excess risk of cancer in renal transplant patients. Transpl Int. 2006 Nov;19(11):908-14. doi: 10.1111/j.1432-2277.2006.00383.x.
PMID: 17018126
citation: Birkeland SA, Lokkegaard H, Storm HH. Cancer risk in patients on dialysis and after renal transplantation. Lancet. 2000 May 27;355(9218):1886-7. doi: 10.1016/s0140-6736(00)02298-4.
PMID: 10866449
citation: Vajdic CM, McDonald SP, McCredie MR, van Leeuwen MT, Stewart JH, Law M, Chapman JR, Webster AC, Kaldor JM, Grulich AE. Cancer incidence before and after kidney transplantation. JAMA. 2006 Dec 20;296(23):2823-31. doi: 10.1001/jama.296.23.2823.
PMID: 17179459
citation: Nyberg G, Eriksson O, Westberg NG. Increased incidence of cervical atypia in women with systemic lupus erythematosus treated with chemotherapy. Arthritis Rheum. 1981 May;24(5):648-50. doi: 10.1002/art.1780240503.
PMID: 7236321
citation: Nath R, Mant C, Luxton J, Hughes G, Raju KS, Shepherd P, Cason J. High risk of human papillomavirus type 16 infections and of development of cervical squamous intraepithelial lesions in systemic lupus erythematosus patients. Arthritis Rheum. 2007 May 15;57(4):619-25. doi: 10.1002/art.22667.
PMID: 17471531
citation: Tam LS, Chan PK, Ho SC, Yu MM, Yim SF, Cheung TH, Wong MC, Li EK. Natural history of cervical papilloma virus infection in systemic lupus erythematosus - a prospective cohort study. J Rheumatol. 2010 Feb;37(2):330-40. doi: 10.3899/jrheum.090644. Epub 2009 Dec 23.
PMID: 20032093
citation: Kirnbauer R, Hubbert NL, Wheeler CM, Becker TM, Lowy DR, Schiller JT. A virus-like particle enzyme-linked immunosorbent assay detects serum antibodies in a majority of women infected with human papillomavirus type 16. J Natl Cancer Inst. 1994 Apr 6;86(7):494-9. doi: 10.1093/jnci/86.7.494.
PMID: 8133532
citation: Joura EA, Kjaer SK, Wheeler CM, Sigurdsson K, Iversen OE, Hernandez-Avila M, Perez G, Brown DR, Koutsky LA, Tay EH, Garcia P, Ault KA, Garland SM, Leodolter S, Olsson SE, Tang GW, Ferris DG, Paavonen J, Lehtinen M, Steben M, Bosch X, Dillner J, Kurman RJ, Majewski S, Munoz N, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan J, Lupinacci LC, Giacoletti KE, Lu S, Vuocolo S, Hesley TM, Haupt RM, Barr E. HPV antibody levels and clinical efficacy following administration of a prophylactic quadrivalent HPV vaccine. Vaccine. 2008 Dec 9;26(52):6844-51. doi: 10.1016/j.vaccine.2008.09.073. Epub 2008 Oct 16.
PMID: 18930097
citation: Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S, Tang GW, Ferris DG, Steben M, Bryan J, Taddeo FJ, Railkar R, Esser MT, Sings HL, Nelson M, Boslego J, Sattler C, Barr E, Koutsky LA; Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE) I Investigators. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med. 2007 May 10;356(19):1928-43. doi: 10.1056/NEJMoa061760.
PMID: 17494926
citation: FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007 May 10;356(19):1915-27. doi: 10.1056/NEJMoa061741.
PMID: 17494925
citation: Mao C, Koutsky LA, Ault KA, Wheeler CM, Brown DR, Wiley DJ, Alvarez FB, Bautista OM, Jansen KU, Barr E. Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia: a randomized controlled trial. Obstet Gynecol. 2006 Jan;107(1):18-27. doi: 10.1097/01.AOG.0000192397.41191.fb. Erratum In: Obstet Gynecol. 2006 Jun;107(6):1425.
PMID: 16394035
citation: Villa LL, Costa RL, Petta CA, Andrade RP, Ault KA, Giuliano AR, Wheeler CM, Koutsky LA, Malm C, Lehtinen M, Skjeldestad FE, Olsson SE, Steinwall M, Brown DR, Kurman RJ, Ronnett BM, Stoler MH, Ferenczy A, Harper DM, Tamms GM, Yu J, Lupinacci L, Railkar R, Taddeo FJ, Jansen KU, Esser MT, Sings HL, Saah AJ, Barr E. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol. 2005 May;6(5):271-8. doi: 10.1016/S1470-2045(05)70101-7.
PMID: 15863374
citation: Ault KA; Future II Study Group. Effect of prophylactic human papillomavirus L1 virus-like-particle vaccine on risk of cervical intraepithelial neoplasia grade 2, grade 3, and adenocarcinoma in situ: a combined analysis of four randomised clinical trials. Lancet. 2007 Jun 2;369(9576):1861-1868. doi: 10.1016/S0140-6736(07)60852-6.
PMID: 17544766
citation: Joura EA, Leodolter S, Hernandez-Avila M, Wheeler CM, Perez G, Koutsky LA, Garland SM, Harper DM, Tang GW, Ferris DG, Steben M, Jones RW, Bryan J, Taddeo FJ, Bautista OM, Esser MT, Sings HL, Nelson M, Boslego JW, Sattler C, Barr E, Paavonen J. Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of three randomised clinical trials. Lancet. 2007 May 19;369(9574):1693-702. doi: 10.1016/S0140-6736(07)60777-6.
PMID: 17512854
citation: Hildesheim A, Herrero R, Wacholder S, Rodriguez AC, Solomon D, Bratti MC, Schiller JT, Gonzalez P, Dubin G, Porras C, Jimenez SE, Lowy DR; Costa Rican HPV Vaccine Trial Group. Effect of human papillomavirus 16/18 L1 viruslike particle vaccine among young women with preexisting infection: a randomized trial. JAMA. 2007 Aug 15;298(7):743-53. doi: 10.1001/jama.298.7.743.
PMID: 17699008
citation: Slade BA, Leidel L, Vellozzi C, Woo EJ, Hua W, Sutherland A, Izurieta HS, Ball R, Miller N, Braun MM, Markowitz LE, Iskander J. Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine. JAMA. 2009 Aug 19;302(7):750-7. doi: 10.1001/jama.2009.1201.
PMID: 19690307
citation: Villa LL, Costa RL, Petta CA, Andrade RP, Paavonen J, Iversen OE, Olsson SE, Hoye J, Steinwall M, Riis-Johannessen G, Andersson-Ellstrom A, Elfgren K, Krogh Gv, Lehtinen M, Malm C, Tamms GM, Giacoletti K, Lupinacci L, Railkar R, Taddeo FJ, Bryan J, Esser MT, Sings HL, Saah AJ, Barr E. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer. 2006 Dec 4;95(11):1459-66. doi: 10.1038/sj.bjc.6603469. Epub 2006 Nov 21.
PMID: 17117182
citation: Olsson SE, Villa LL, Costa RL, Petta CA, Andrade RP, Malm C, Iversen OE, Hoye J, Steinwall M, Riis-Johannessen G, Andersson-Ellstrom A, Elfgren K, von Krogh G, Lehtinen M, Paavonen J, Tamms GM, Giacoletti K, Lupinacci L, Esser MT, Vuocolo SC, Saah AJ, Barr E. Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine. Vaccine. 2007 Jun 21;25(26):4931-9. doi: 10.1016/j.vaccine.2007.03.049. Epub 2007 Apr 20.
PMID: 17499406
citation: Reisinger KS, Block SL, Lazcano-Ponce E, Samakoses R, Esser MT, Erick J, Puchalski D, Giacoletti KE, Sings HL, Lukac S, Alvarez FB, Barr E. Safety and persistent immunogenicity of a quadrivalent human papillomavirus types 6, 11, 16, 18 L1 virus-like particle vaccine in preadolescents and adolescents: a randomized controlled trial. Pediatr Infect Dis J. 2007 Mar;26(3):201-9. doi: 10.1097/01.inf.0000253970.29190.5a.
PMID: 17484215
citation: Levin MJ, Moscicki AB, Song LY, Fenton T, Meyer WA 3rd, Read JS, Handelsman EL, Nowak B, Sattler CA, Saah A, Radley DR, Esser MT, Weinberg A; IMPAACT P1047 Protocol Team. Safety and immunogenicity of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine in HIV-infected children 7 to 12 years old. J Acquir Immune Defic Syndr. 2010 Oct;55(2):197-204. doi: 10.1097/QAI.0b013e3181de8d26.
PMID: 20574412
citation: Grabowska K, Wang X, Jacobsson A, Dillner J. Evaluation of cost-precision rations of different strategies for ELISA measurement of serum antibody levels. J Immunol Methods. 2002 Dec 20;271(1-2):1-15. doi: 10.1016/s0022-1759(02)00334-4.
PMID: 12445724
citation: Dessy FJ, Giannini SL, Bougelet CA, Kemp TJ, David MP, Poncelet SM, Pinto LA, Wettendorff MA. Correlation between direct ELISA, single epitope-based inhibition ELISA and pseudovirion-based neutralization assay for measuring anti-HPV-16 and anti-HPV-18 antibody response after vaccination with the AS04-adjuvanted HPV-16/18 cervical cancer vaccine. Hum Vaccin. 2008 Nov-Dec;4(6):425-34. doi: 10.4161/hv.4.6.6912. Epub 2008 Nov 11.
PMID: 18948732
citation: Waterboer T, Sehr P, Michael KM, Franceschi S, Nieland JD, Joos TO, Templin MF, Pawlita M. Multiplex human papillomavirus serology based on in situ-purified glutathione s-transferase fusion proteins. Clin Chem. 2005 Oct;51(10):1845-53. doi: 10.1373/clinchem.2005.052381. Epub 2005 Aug 11.
PMID: 16099939
citation: Michael KM, Waterboer T, Sehr P, Rother A, Reidel U, Boeing H, Bravo IG, Schlehofer J, Gartner BC, Pawlita M. Seroprevalence of 34 human papillomavirus types in the German general population. PLoS Pathog. 2008 Jun 20;4(6):e1000091. doi: 10.1371/journal.ppat.1000091.
PMID: 18566657
citation: Mendez F, Munoz N, Posso H, Molano M, Moreno V, van den Brule AJ, Ronderos M, Meijer C, Munoz A; Instituto Nacional de Cancerologia Human Papillomavirus Study Group. Cervical coinfection with human papillomavirus (HPV) types and possible implications for the prevention of cervical cancer by HPV vaccines. J Infect Dis. 2005 Oct 1;192(7):1158-65. doi: 10.1086/444391. Epub 2005 Aug 29.
PMID: 16136457
responsible party type: Sponsor
mesh term: Lupus Erythematosus, Systemic
mesh term: Immune System Diseases