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)
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 170
- 试验地点
- 1
- 主要终点
- Rate of seroconversion in HPV antibodies against HPV
研究概览
简要总结
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.
详细描述
Number of patients:
Study: 200 patients: 50 in the first open label phase (june 2018 to dec 2018), then n=150 in the randomized phase starting in January 2019 Substudy on immune response analysis in a subset of patients: 40 patients and separated informed consent
Primary outcome:
Rate of seroconversion of neutralizing antibodies against each HPV vaccine genotypes namely 6/11/16/18/31/33/45/52/58 among women seronegative at baseline for HPV vaccine genotypes, by measuring neutralizing antibody against the 9 vaccine genotypes of HPV at baseline, month 7. The measure will be performed on a 10 ml tube by chemiluminescence immunoassay (cLIA) technique in Merck laboratory .Comparison of that rate at month 7 (non inferiority defined as at least 80% of seroconversion in ARM A).
Secondary outcomes:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 15 Years 至 40 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
ARM B: 3 doses (0, 2 and 6 months)
ARM B: All patients will receive the 9-valent vaccine against HPV (Gardasil9) 3 doses at 0,2 and 6 months intramuscularly
干预措施: Vaccine (Biological)
ARM A: 2 doses (0 and 6 months )
ARM A: All patients will receive the 9-valent vaccine against HPV (Gardasil9) 2 doses at 0 and 6 months intramuscularly. A third facultative dose will be given if antibodies measured at month 7 are insufficent.
干预措施: Vaccine (Biological)
结局指标
主要结局
Rate of seroconversion in HPV antibodies against HPV
时间窗: Month 7
The rate of seroconversion of specific neutralizing antibodies against each HPV vaccine genotypes (6/11/16/18/31/33/45/52/58) one month after completion of a three doses schedule (0, 2 and 6 months) in women seronegative at baseline for these antibodies.
次要结局
- Incidence of Treatment-Emergent Adverse Events (Safety and tolerability of the vaccines).(day 2 to 7 after each vaccine administration)
- Impact of vaccine administration on T-lymphocyte CD4+ cell count and HIV viremia(Month 7)
- Measure of the geometric mean titre of specific neutralizing antibodies against each HPV vaccine genotypes (6/11/16/18/31/33/45/52/58).(Month 7)
- Cellular immune response(Month 7)
- Incidence and prevalence rates of HPV infections(Month 18, 24,36,48 and 60)
- The incidence and prevalence rates of abnormal cervical cytology(Month 18)
- Completion of vaccine schedule.(Month 7)
研究者
Deborah Konopnicki
Head of clinic, Infectious Diseases Department
Centre Hospitalier Universitaire Saint Pierre