Prospective Longitudinal Study on Immunogenicity, Induction of Cellular Immune Responses and Safety of Vaccination Against HPV With the 9-valent Vaccine in HIV-positive Women (The Papillon Study)

CE/17-12-06

Phase IV prospective study measuring the immunogenicity (neutralizing antibody titles against each HPV vaccine genotype) of the 9-valent vaccine against HPV (Gardasil9®Merck) in HIV-positive women aged 15-40 years with fully suppressed HIV viremia on combined antiretroviral therapy. After a first open phase evaluating tolerability of Gardasil9 (from June 2018 to December 2018), an amendment was introduced to randomize women between two different doses schedules: in the first schedule (ARM A), women will receive 2 doses at time 0 and 6 months and a third dose between 18-48 months if their antibody levels are insufficient; the second schedule (ARM B) will be 3 doses at 0, 2 and 6 months. Primary outcome is the non-inferiority of the rate of seroconversion against each HPV vaccine genotypes in women seronegative at baseline after either 2 or 3 doses of vaccination (month 7). Secondary outcomes are rate of seroconversion after 3 doses if they have received a third dose, completion of vaccine schedule, vaccine safety, antibody titles, and induction of cellular immunity against HPV contained in the vaccine, incidence of cervical HPV infection and incidence of abnormal cytology after vaccination. The safety of the vaccination (local or systemic reaction and impact on HIV viral control and immunodeficiency level) will be assessed. The cellular immune response will be assessed in a subgroup of patients.

2018-01-08

2023-05-02

2026-05-02

Active (not recruiting)

Early phase I

170

Inclusion Criteria: * HIV-positive woman * Age 15-40 years * Undetectable HIV viral load (HIVRNA \<400 cp/ml) for at least 6 months (i,e: having at least two separate HIVRNA \<400 cp/ml at 6 months intervals; the most recent HIVRNA \<400 cp/ml may be performed with the baseline sample for the study). * No planned pregnancy foreseen for the next 7 months and use of contraception such as condom, hormonal contraception or intrauterine device * IC signed Exclusion Criteria: * Previous hysterectomy or conisation * Previous or current biopsy-proven cervical, vulvar or vaginal HPV-associated lesion defined as ≥ cervical intraepithelial neoplasia grade 2(CIN2) ) , Vulvar intraepithelial neoplasia grade 2 (VIN2), vaginal intraepithelial neoplasia grade 2 (VaIN2 ) or invasive carcinoma * Previous vaccination against HPV (at least one dose) * Ongoing or planned pregnancy foreseen in the next 7 months * Other immunodeficiency conditions such as ongoing or previous (within 6 months) chemotherapy against cancer or chronic systemic corticosteroids treatment or immunosuppressive therapy after transplantation * Any condition contraindicating intramuscular injection such as warfarin therapy.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'After a first open label phase evaluating tolerability of Gardasil9 in HIV-positive women and where all patients (n=50) have received three doses (0,2 and 6 months) of the 9valent vaccine against HPV from June 2018 to end of December 2018, the study will randomize participants between two between two different doses schedules: in the first schedule (ARM A), women will receive 2 doses at time 0 and 6 months and a third dose between 18-48 months if their antibody levels are insufficient; the second schedule (ARM B) will be 3 doses at 0, 2 and 6 months.', 'primaryPurpose': 'PREVENTION', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 170, 'type': 'ACTUAL'}}

2024-02-07