Quadrivalent HPV Vaccination After Effective Treatment of Anal Intraepithelial Neoplasia in HIV+ Men
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 126
- 试验地点
- 3
- 主要终点
- Cumulative recurrence of intra-anal or peri-anal HG AIN at 12 months after the last vaccination (18 months after inclusion), as assessed by HRA, with biopsies taken of suspect lesions.
研究概览
简要总结
This study evaluates vaccination with the quadrivalent HPV vaccine (Gardasil) versus placebo vaccination on prevention of high grade AIN recurrence in HIV-positive MSM (men who have sex with men) who were successfully treated for high grade AIN.
详细描述
Rationale: Since the introduction of combination antiretroviral therapy (cART), human immunodeficiency virus (HIV)-related morbidity and mortality have considerably decreased. However, as a result of the significantly prolonged life span, new causes of morbidity and mortality have become evident. In particular, anal cancer incidence has increased dramatically in HIV-positive men. Like cervical cancer, anal cancer is causally linked to infections with high-risk papillomaviruses, and is preceded by precursor lesions: anal intraepithelial neoplasia (AIN). Over 90% of HIV-positive MSM (men who have sex with men) have persisting anal HPV (human papilloma virus) infection, and high-grade (HG) AIN is present in 30% of all HIV+ MSM.
As in cervical intraepithelial neoplasia, early diagnosis and treatment of AIN have been advocated to prevent malignancy. Electrocoagulation/ cauterization is standard of care for intra-anal AIN, but after treatment, recurrence of lesions occurs in approx. 50% of cases. This is a major problem in an effective screening program for AIN.
In a nonconcurrent, non-blinded cohort study qHPV (quadrivalent human papilloma virus) vaccination significantly (HR 0.50) reduced HG AIN recurrence among MSM successfully treated for AIN. This is in accordance with findings in women treated for cervical intraepithelial neoplasia. Previous vaccination with quadrivalent HPV vaccine among women who had surgical treatment for HPV related disease significantly reduced the incidence of subsequent HPV related disease, including high grade disease.
Therefore, a strategy that is worth investigating is vaccination with the qHPV vaccine to prevent recurrences in HIV+ MSM who were successfully treated for HG AIN.
Objective: The primary objective of the current study is to assess the efficacy of qHPV vaccination in preventing recurrence of high-grade AIN in HIV+ MSM with CD4 counts >350 x 10E6/l who were successfully treated for high-grade intra-anal AIN in the past year.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Written informed consent.
- •Age ≥ 18 years.
- •HIV+ MSM, CD4 count > 350/ul (maximum 6 months before screening visit).
- •Biopsy-proven intra-anal high-grade AIN successfully treated in the past year with cauterization, cryotherapy, Efudix, imiquimod or another form of local treatment. A maximum interval of 1 year between last treatment and first vaccination is allowed. Lesions with regression from HG to LG AIN (AIN 1) will also be eligible.
- •Lesions (still) in remission:
- •Remission has to be established by 2 independent HRA anoscopists.
- •A maximum interval of 3 months is allowed between the first of these HRAs and the first vaccination, and a maximum interval of 6 weeks is allowed between the second of these HRAs and the first vaccination.
- •Biopsies of suspect lesions need to be obtained in one of the HRA sessions.
- •Good performance status (a Karnofsky performance score of ≥ 60 [on a scale of 0 to 100, with higher scores indicating better performance status]).
- •Pre-treatment haematology, and plasma ASAT, ALAT and creatinine levels compatible with study inclusion (maximum 6 weeks before screening visit).
- •Exclusion criteria:
- •Immunosuppressive medication or other diseases associated with immunodeficiency.
- •Life expectancy less than one year.
- •Previous HPV vaccination.
- •History of anal cancer.
- •Other diseases not compatible with study participation.
- •Allergy against constituent of Gardasil ® vaccine.
- •Currently peri-anal AIN2 or 3.
排除标准
- 未提供
研究组 & 干预措施
Placebo
Intramuscular Saline 0.9% vaccination at 0, 2 and 6 months
干预措施: Placebo (Drug)
Gardasil
Gardasil
干预措施: Gardasil (Biological)
结局指标
主要结局
Cumulative recurrence of intra-anal or peri-anal HG AIN at 12 months after the last vaccination (18 months after inclusion), as assessed by HRA, with biopsies taken of suspect lesions.
时间窗: 18 months
次要结局
- Cumulative occurrence of intra-anal or peri-anal LG AIN at 12 months after the last vaccination.(18 months)
- Cumulative occurrence of anogenital warts at 12 months after the last vaccination.(18 months)
- HPV type-specific antibody response.(9 months (3 months after last vaccination))
- Toxicity/ safety of the Gardasil vaccine in HIV+ MSM.(18 months)
- Recurrence of intra-anal or peri-anal HG AIN at the moment of last vaccination and 6 months afterwards.(6 and 12 months)
- Causative HPV type in recurrent AIN lesions, as assessed by LCM/ PCR.(18 months)
研究者
Prof. Jan Prins
Professor. dr. J.M. Prins
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)