A Non-Randomized, Open-Label Study to Assess the Reduction of Human Papillomavirus (HPV) Viral Infectivity and Transmission in HPV16/18-Positive Women Before and After Vaccination with 9vHPV, a Multivalent L1 Virus-like Particle Vaccine, Evaluated in Cervical, Anal, Vulvar, Urine and Oral Samples Obtained After One, Two, and Three Vaccine Doses (RIFT-HPV1/RIFT-HPV2).
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 69
- 试验地点
- 2
- 主要终点
- In-vitro infectivity evaluation (by expression of E1^E4 HPV biomarker in HaCaT keratinocytes) of cervical, anal, vulvar, urine and oral samples collected before and after 9vHPV vaccination.
研究概览
简要总结
The main objective of the study is to demonstrate the reduction in infective capacity of body fluids (cervical, anal, urine, vulvar and oral samples) in adult women at least HPV 16 and/or, 18 positive after vaccination with 9vHPV in a three-dose regimen
入排标准
- 年龄范围
- 18 years 至 64 years（18-64 Years）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Are women, aged 18 years or older for cohort 1 and cohort 2 , attending a routine cervical cancer screening visit or gynecological visit, are positive for HPV16 and/or HPV18 have been recently diagnosed for their HPV-positivity (within the last 10 months) and meet one of the following criteria: RIFT-HPV 1 cohort: non-vaccinated adult women aged 18 years or older, positive on cervix for HPV 16 and/or 18, with non apparent cervical lesion or with cervical lesion , eligible for conservative treatment. RIFT-HPV 2 cohort: non-vaccinated adult women aged 18 years or older, positive for HPV 16 and/or HPV 18 anal test with non-apparent anal lesions or with anal lesions eligible for conservative treatment. Or non-vaccinated adult women aged 18 years or older, positive for HPV 16 and/or HPV 18 cervical test with vulvar premalignant lesion or condylomas, associated to HPV infection.
- •Are judged to have no major health conditions (based on medical history, physical examination, and laboratory testing) that may compromise their capacity to comply with study procedures, as per Investigator’s judgement.
- •Provide written informed consent for their participation in the study.
- •Provide a frequent contact telephone number as well as an alternate means of contact (such as an alternate telephone number or email) for follow-up purposes.
- •Are planning to stay in their area of residence (near the study site) for the full duration of the study, so it is convenient for them to attend study visits at the site.
排除标准
- •Have any cervical lesion that requires clinical intervention within 7 months that could significantly affect cervical epithelia (and therefore, HPV viral production), such as cervical conization (RIFT-HPV Cohort 1).
- •Are, at the time of signing informed consent, using recreational or illicit drugs or have had a recent history (within the last year) of drug or alcohol abuse or dependence at the discretion of the Investigator that might interfere with her capacity to comply with study procedures. Alcohol abusers are defined as those who drink despite recurrent social, interpersonal, and/or legal problems because of alcohol use.
- •Have a fever (defined as temperature ≥37.8°C) within the 24-hour period prior to the Day 1 visit (Visit 1)*.
- •Have a history of severe allergic reaction (e.g., swelling of the mouth and throat, difficulty breathing, hypotension, or shock) that required medical intervention.
- •Are allergic to any vaccine component, including aluminium, yeast, or BENZONASETM (nuclease, Nicomedia [used to remove residual nucleic acids from this and other vaccines]). For this exclusion criterion, an allergy to vaccine components is defined as an allergic reaction that met the criteria for severe adverse event (SAE), defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or results in persistent or significant disability/incapacity.
- •Have known thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injection of study vaccine.
- •Have a history of splenectomy.
- •Have a history of ano-genital cancer or HPV-related head and neck cancer.
- •Are pregnant at the time of signing informed consent, are planning to become pregnant within the full duration of the study.
- •Have a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might confound the results of the study or interfere with the subject’s compliance of study procedures for the full duration of the study, such that their inclusion in the study is not in the best interest of the subject and/or may compromise fulfilment of study’s objectives, by judgement of the Investigator.
结局指标
主要结局
In-vitro infectivity evaluation (by expression of E1^E4 HPV biomarker in HaCaT keratinocytes) of cervical, anal, vulvar, urine and oral samples collected before and after 9vHPV vaccination.
In-vitro infectivity evaluation (by expression of E1^E4 HPV biomarker in HaCaT keratinocytes) of cervical, anal, vulvar, urine and oral samples collected before and after 9vHPV vaccination.
Detection of HPV 6/11/16/18/31/33/45/52/58 L1 antibodies in cervical, anal, vulvar, urine and oral samples collected before and after 9vHPV vaccination, using: -ELISA for types 16 and 18 in samples from RIFT-HPV 1 and 2 study cohorts, -cLIA for all 9vHPV-covered types in samples from RIFT-HPV 1 study cohort. This endpoint will allow associating the reduction in viral infectivity with the presence of neutralizing antibodies.
Detection of HPV 6/11/16/18/31/33/45/52/58 L1 antibodies in cervical, anal, vulvar, urine and oral samples collected before and after 9vHPV vaccination, using: -ELISA for types 16 and 18 in samples from RIFT-HPV 1 and 2 study cohorts, -cLIA for all 9vHPV-covered types in samples from RIFT-HPV 1 study cohort. This endpoint will allow associating the reduction in viral infectivity with the presence of neutralizing antibodies.
-HPV16/18 virion detection (using ELISA, electronic microscopy) and HPV DNA detection and genotyping (using Anyplex/Allplex HPV28) in cervical, anal, vulvar, urine and oral samples collected before and after 9vHPV vaccination. This endpoint will allow to identify samples of subjects with a nonproductive viral infection or undergoing natural clearance, and distinguish them from samples of subjects with productive but reduced infection due to 9vHPV vaccination.
-HPV16/18 virion detection (using ELISA, electronic microscopy) and HPV DNA detection and genotyping (using Anyplex/Allplex HPV28) in cervical, anal, vulvar, urine and oral samples collected before and after 9vHPV vaccination. This endpoint will allow to identify samples of subjects with a nonproductive viral infection or undergoing natural clearance, and distinguish them from samples of subjects with productive but reduced infection due to 9vHPV vaccination.
次要结局
- -HPV 6/11/16/18/31/33/45/52/58 L1 antibody titration in serum samples collected before and after 9vHPV vaccination, using: -ELISA for types 16 and 18 in samples from RIFT-HPV 1 and 2 study cohorts, -cLIA for all 9vHPV-covered types in samples from RIFT-HPV 1 study cohort.
研究者
Miguel Ángel Pavón Ribas
Scientific
Bellvitge University Hospital