Clinical trial NCT01687192: Multicenter Trial Evaluating the Immunogenicity of HPV Vaccination in Girls on Immunosuppressive Therapy.
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Transplantation
Systemic Lupus Erythematosus
Systemic Immune Disease
Keywords: Seroconversion
Immunosuppressed treatment
HPV vaccination
Immunogenicity
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2012-09-18
Enrollment: 37
Sex: FEMALE
Minimum age (years): 9
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.

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 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

Primary outcomes:
measure: Seroconversion rate for HPV 16 and 18 at M18
timeFrame: 18 months after first dose of vacinne (i.e. Inclusion visit)
Secondary outcomes:
measure: Geometric means of anti-HPV 6, 11, 16 and 18 antibody titers at M7, M18, and M36, respectively.
timeFrame: 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
timeFrame: 7 and 18 months after first dose of vaccine
measure: Proportion of patients with genital warts or cervical lesions (if relevant)
timeFrame: 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
timeFrame: Assessed at months 2,6,7 and 18 after first dose of vaccine
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux, Hôpital Pellegrin-Enfants
city: Bron
country: France
facility: HCLyon, Hôpital Femme-mère-enfant
city: Lille
country: France
facility: CHU de Lille, Hôpital Jeanne de Flandres
city: Montpellier
country: France
facility: CHU de Montpellier, Hôpital Arnaud de Villeneuve
city: Nantes
country: France
facility: CHU de Nantes, Hôpital Mère-Enfants
city: Paris
country: France
facility: AP-HP, Hôpital Robert Debré
city: Paris
country: France
facility: AP-HP, Hôpital Armand Trousseau
city: Paris
country: France
facility: AP-HP, Hôpital Necker-Enfants
city: Toulouse
country: France
facility: CHU de Toulouse, Hôpital des Enfants
Study officials:
affiliation: University Hospital, Bordeaux, USMR
name: Geneviève CHENE, MD-PhD
role: STUDY_CHAIR
affiliation: University Hospital, Bordeaux
name: Jerome HARAMBAT, MD
role: PRINCIPAL_INVESTIGATOR
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