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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Multicenter Clinical Trial Evaluating the Immunological Response of Vaccination Against Infection by Human Papillomavirus (HPV) 6, 11, 16, 18 in Girls Receiving Immunosuppressive Therapy.

Conditions
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Transplantation, Systemic Lupus Erythematosus, Systemic Immune Disease

Intervention / Treatment
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* Biological: HPV prophylactic vaccine Gardasil


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Girls and young womens receiving immunosuppressive treatment<br> | Biological: HPV prophylactic vaccine Gardasil<br>* 3 injections: at Inclusion visit then 2 and 6 months after.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion rate for HPV 16 and 18 at M18 |  | 18 months after first dose of vacinne (i.e. Inclusion visit) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric means of anti-HPV 6, 11, 16 and 18 antibody titers at M7, M18, and M36, respectively. |  | Samples collected 7, 18 and 36 months after first dose of vaccine | 
| Proportion of patients with a good cell response at M7 and M18 |  | 7 and 18 months after first dose of vaccine | 
| Proportion of patients with genital warts or cervical lesions (if relevant) |  | 36 months after first dose of vaccine | 
| Number, type and time of occurrence of adverse events of any grade during 18 months after first dose of vaccine |  | Assessed at months 2,6,7 and 18 after first dose of vaccine | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Seroconversion, Immunosuppressed treatment, HPV vaccination, Immunogenicity