Multicenter Trial Evaluating the Immunogenicity of HPV Vaccination in Girls on Immunosuppressive Therapy. (PRIMAVERA)

This study is currently recruiting participants.

Verified December 2012 by University Hospital, Bordeaux

Sponsor:

Information provided by (Responsible Party):

University Hospital, Bordeaux

ClinicalTrials.gov Identifier:

NCT01687192

First received: September 13, 2012

Last updated: December 5, 2012

Last verified: December 2012

History of Changes

Purpose

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.

Condition	Intervention	Phase
Transplantation Systemic Lupus Erythematosus Systemic Immune Disease	Biological: HPV prophylactic vaccine Gardasil	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: Open Label
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.

Resource links provided by NLM:

MedlinePlus related topics: Lupus

U.S. FDA Resources

Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:

Seroconversion rate for HPV 16 and 18 at M18 [ Time Frame: 18 months after first dose of vacinne (i.e. Inclusion visit) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
Proportion of patients with a good cell response at M7 and M18 [ Time Frame: 7 and 18 months after first dose of vaccine ] [ Designated as safety issue: No ]
Proportion of patients with genital warts or cervical lesions (if relevant) [ Time Frame: 36 months after first dose of vaccine ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	35
Study Start Date:	October 2012
Estimated Study Completion Date:	August 2016
Estimated Primary Completion Date:	February 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Girls and young womens receiving immunosuppressive treatment	Biological: HPV prophylactic vaccine Gardasil 3 injections: at Inclusion visit then 2 and 6 months after.

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	9 Years to 18 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Female gender
Age ≥ 9 years and < 18 years
Weight ≥ 25 kg
Solid organ transplantation: kidney, liver, heart, lung, intestinal or combined transplant; or systemic lupus erythematosus or other systemic immune disease
Transplantation or diagnosis of lupus or diagnosis of systemic immune disease since more than 6 months
Immunosuppressant treatment by anti-metabolites or calcineurin inhibitors, with or without associated corticosteroids
Minimum required period of 3 months considered as stable after transplantation or without relapse of lupus according to physician evaluation
In case of sexual activity (assessed by auto-declaration): onset less than one year before inclusion
Written informed consent signed by the investigator and the legal representatives of the patient, and assent by the patient

Exclusion Criteria:

Male gender
Pregnancy
Age < 9 years or ≥ 18 years
Previous HPV vaccination
Immunosuppressive treatment by anti-TNF (adalimumab, etanercept, infliximab) or monoclonal antibodies (rituximab, anakinra, abatacept) during the last 3 months
Active malignancy
Active opportunistic infection
HIV infection
Concurrent clinical trial

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01687192

Contacts

Contact: Jerome HARAMBAT, MD	(0)556798725 ext +33	jerome.harambat@chu-bordeaux.fr
Contact: Guillaume SIMON, CRA	(0)5 57 82 00 03 ext +33	guillaume.simon@chu-bordeaux.fr

Locations

France
CHU de Bordeaux, Hôpital Pellegrin-Enfants	Recruiting
Bordeaux, France, 33076
Contact: Guillaume SIMON, CRA (0)5 57 82 00 03 ext +33 guillaume.simon@chu-bordeaux.fr
Principal Investigator: Jerome HARAMBAT, MD
Sub-Investigator: Brigitte LLANAS, MD
Sub-Investigator: Thierry LAMIREAU, MD
HCLyon, Hôpital Femme-mère-enfant	Recruiting
Bron, France, 69677
Contact: Pierre COCHAT, MD (0)4 72 11 03 46 ext +33 pierre.cochat@chu-lyon.fr
Principal Investigator: Pierre COCHAT, MD
Sub-Investigator: Bruno RANCHIN, MD
Sub-Investigator: Christine RIVET, MD
Sub-Investigator: Alexandre BELOT, MD
CHU de Lille, Hôpital Jeanne de Flandres	Not yet recruiting
Lille, France, 59037
Contact: Annie LAHOCHE, MD (0)3 20 44 46 95 ext +33 annie.lahoche@chru-lille.fr
Principal Investigator: Annie LAHOCHE, MD
Sub-Investigator: Maud DEHENNAULT, MD
Sub-Investigator: Frédéric GOTTRAND, MD
Sub-Investigator: Valérie LEROY, MD
CHU de Limoges, Hôpital Mère Enfant	Not yet recruiting
Limoges, France, 87042
Contact: Vincent GUIGONIS, MD (0)5 55 05 63 58 ext +33 vincent.guigonis@chu-limoges.fr
Principal Investigator: Vincent GUIGONIS, MD
AP-HM Hôpital Timone-Enfants	Not yet recruiting
Marseille, France, 13385
Contact: Florentine GARAIX, MD (0)4 91 38 67 42 ext +33 florentine.garaix@ap-hm.fr
Principal Investigator: Florentine GARAIX, MD
Sub-Investigator: Michel TSIMARATOS, MD
Sub-Investigator: Bernard KREITMANN, MD
CHU de Montpellier, Hôpital Arnaud de Villeneuve	Not yet recruiting
Montpellier, France, 34295
Contact: Denis MORIN, MD (0)4 67 33 66 07 ext +33 d-morin@chu-montpellier.fr
Principal Investigator: Denis MORIN, MD
CHU de Nantes, Hôpital Mère-Enfants	Not yet recruiting
Nantes, France, 44093
Contact: Gwenaëlle ROUSSEY, MD (0)2 40 08 34 80 ext +33 gwenaelle.roussey@chu-nantes.fr
Principal Investigator: Gwenaëlle ROUSSEY-KESLER, MD
Sub-Investigator: Emma ALLAIN-LAUNAY, MD
AP-HP, Hôpital Armand Trousseau	Not yet recruiting
Paris, France, 75571
Contact: Tim ULINSKI, MD (0)1 44 73 66 62 ext +33 tim.ulinski@trs.aphp.fr
Principal Investigator: Tim ULINSKI, MD
AP-HP, Hôpital de La Pitié-Salpêtrière	Not yet recruiting
Paris, France, 75013
Contact: Zahir AMOURA, MD (0)1 42 17 80 01 ext +33 zahir.amoura@psl.aphp.fr
Principal Investigator: Zahir AMOURA, MD
AP-HP, Hôpital Necker-Enfants	Not yet recruiting
Paris, France, 75743
Contact: Dominique DEBRAY, MD (0)1 44 49 25 60 ext +33 dominique.debray@nck.aphp.fr
Principal Investigator: Dominique DEBRAY, MD
Sub-Investigator: Rémi SALOMON, MD
Sub-Investigator: Genevieve GUEST, MD
Sub-Investigator: Marina CHARBIT, MD
Sub-Investigator: Brigitte BADER-MEUNIER, MD
AP-HP, Hôpital Robert Debré	Not yet recruiting
Paris, France, 75019
Contact: Marie-Alice MACHER, MD (0)1 40 03 23 98 ext +33 marie-alice.macher@rdb.aphp.fr
Principal Investigator: Marie-Alice MACHER, MD
Sub-Investigator: Georges DESCHENES, MD
Sub-Investigator: Véronique BAUDOUIN, MD
Sub-Investigator: Anne MAISIN, MD
CHU de Strasbourg, Hôpital de Hautepierre	Not yet recruiting
Strasbourg, France, 67098
Contact: Michel FISCHBACH, MD (0)3 88 12 77 43 ext +33 michel.fischbach@chru-strasbourg.fr
Principal Investigator: Michel FISCHBACH, MD
CHU de Toulouse, Hôpital des Enfants	Not yet recruiting
Toulouse, France, 31059
Contact: Stéphane DECRAMER, MD (0)5 34 55 86 64 ext +33 decramer.s@chu-toulouse.fr
Principal Investigator: Stéphane DECRAMER, MD
Sub-Investigator: Arnaud GARNIER, MD
Sub-Investigator: Pierre BROUE, MD

Sponsors and Collaborators

University Hospital, Bordeaux

Investigators

Study Chair:	Geneviève CHENE, MD-PhD	University Hospital, Bordeaux, USMR
Principal Investigator:	Jerome HARAMBAT, MD	University Hospital, Bordeaux

More Information

Publications:

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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. Erratum in: Am J Epidemiol. 2003 May 1;157(9):858.

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.

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.

Penn I. Occurrence of cancers in immunosuppressed organ transplant recipients. Clin Transpl. 1998;:147-58.

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.

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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.

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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.

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. Epub 2009 Dec 23.

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.

Joura EA, Kjaer SK, Wheeler CM, Sigurdsson K, Iversen OE, Hernandez-Avila M, Perez G, Brown DR, Koutsky LA, Tay EH, García 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, Muñoz 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. Epub 2008 Oct 16.

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.

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.

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. Erratum in: Obstet Gynecol. 2006 Jun;107(6):1425.

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.

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):1861-8.

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.

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.

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.

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 G, 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. Epub 2006 Nov 21.

Olsson SE, Villa LL, Costa RL, Petta CA, Andrade RP, Malm C, Iversen OE, Høye 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. Epub 2007 Apr 20.

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.

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; for the 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 Jun 22; [Epub ahead of print]

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.

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. Epub 2008 Nov 11.

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. Epub 2005 Aug 11.

Michael KM, Waterboer T, Sehr P, Rother A, Reidel U, Boeing H, Bravo IG, Schlehofer J, Gärtner BC, Pawlita M. Seroprevalence of 34 human papillomavirus types in the German general population. PLoS Pathog. 2008 Jun 20;4(6):e1000091.

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Responsible Party:	University Hospital, Bordeaux
ClinicalTrials.gov Identifier:	NCT01687192 History of Changes
Other Study ID Numbers:	CHUBX 2011/18
Study First Received:	September 13, 2012
Last Updated:	December 5, 2012
Health Authority:	France: L’Agence nationale de sécurité du médicament et des produits de santé

Keywords provided by University Hospital, Bordeaux:

Seroconversion
Immunosuppressed treatment
HPV vaccination
Immunogenicity

Additional relevant MeSH terms:

Immune System Diseases
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases

Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013

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