四价人乳头瘤病毒疫苗在中国境内9~26岁女性中的免疫原性和安全性研究:一项开放性、免疫桥接Ⅲ期临床试验

Immunogenicity and safety of the quadrivalent human papillomavirus vaccine in Chinese females aged 9 to 26 years:A phase 3,open-label,immunobridging study

目的四价人乳头瘤病毒疫苗(quadrivalent human papillomavirus,qHPV;HPV6/11/16/18型,临床试验注册号NCT03493542)于2017年在中国境内获批上市,适用于20~45岁女性。这项开放性Ⅲ期临床试验旨在评估并比较9~19岁和20~26岁中国境内女性四价HPV疫苗自第1剂接种至第7个月的免疫原性和安全性。方法9~26岁的受试者分别于第1天、第2个月和第6个月接种3剂次四价HPV疫苗。使用竞争性荧光免疫检测法(cLIA)分析首剂接种当天和第7个月时受试者血清样本中的抗-HPV6/11/16/18抗体几何平均滴度(GMT)和血清抗体阳转率。记录接种后30 d内的注射部位不良事件和全身性不良事件以及整个研究期间出现的严重不良事件。结果本研究共纳入766例接种至少1剂受试者(9~19岁组与20~26岁组各383例)。两个年龄组中所有符合免疫原性方案的受试者在第7个月时,疫苗所含四种HPV型别均产生血清学抗体阳转。9~19岁年龄组受试者在第7个月时产生的抗-HPV6/11/16/18 GMT值非劣效于20~26岁组受试者。9~19岁年龄组中,分别有36.6%和49.3%的受试者报告注射部位不良事件和全身性不良事件,20~26岁年龄组受试者中注射部位和全身性不良事件比例分别为40.7%和54.8%。没有发生疫苗相关严重不良事件。无受试者因不良事件终止研究,无死亡病例的报告。结论9~19岁中国境内女性中接种3剂次四价HPV疫苗后产生的抗体水平非劣效于20~26岁年龄组。该疫苗在研究人群中具有良好的耐受性。

Objective The quadrivalent human papillomavirus(qHPV;HPV6/11/16/18)vaccine was approved for use in Chinese women aged 20-45 years in 2017.This Phase 3,open-label study(NCT03493542)was aimed to assess the immunogenicity and safety of the qHPV vaccine in Chinese girls aged 9-19 years versus Chinese young women aged 20-26 years from Day 1 through Month 7.Methods Participants aged 9-26 years received three doses of the qHPV vaccine(Day 1,Month 2,Month6).Geometric mean titers(GMTs)and seroconversion percentages for anti-HPV6/11/16/18 antibodies were determined by competitive Luminex immunoassay(cLIA)in serum samples obtained on Day 1 and at Month 7.Injection-site adverse events(AEs)and systemic AEs within 30 days post-vaccination,and serious AEs(SAEs)occurring at any time during the study were recorded.Results In total,766 participants(383 aged 9-19 years;383 aged 20-26 years)were enrolled and received≥1 vaccine dose.All participants in the per-protocol immunogenicity population of two groups had seroconverted to each of the vaccine HPV types at Month 7.Anti-HPV6/11/16/18 antibody GMTs at Month 7 in participants aged 9-19 years were non-inferior to those in participants aged 20-26 years.Injection-site AEs and systemic AEs were reported by 36.6%and 49.3%in 9-19-year-olds group,40.7%and 54.8%in 20-26-year-olds group respectively.There were no vaccine-related SAEs.There was no participant discontinued the vaccine due to an AE and no deaths were reported.Conclusion Antibody responses induced by the 3-dose qHPV vaccination regimen in Chinese girls aged 9-19 years were non-inferior to those in Chinese young women aged 20-26 years.The vaccine was generally well tolerated in the study population.