Human Papillomavirus MedDRA version: 20.1 Level: LLT Classification code 10063001 Term: Human papilloma virus infection System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Gardasil 9
Pharmaceutical Form: Suspension for injection
Sponsors
Dr. Miguel Angel Pavón Ribas
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Are women, aged 35 or 27 years or older for cohort 1 and cohort 2 respectively, attending a routine cervical cancer screening visit or gynaecological visit, are positive for HPV16, 18 or double-positive for 16 and 18 and negative for the rest of high-risk HPV types in a cervical sample, have been recently diagnosed for their HPV-positivity (within the last 24 months) and meet one of the following criteria: - have no apparent cervical lesion (cohort 1). - have a CIN1/2 lesion which is eligible for conservative treatment (cohort 1). - have multiple cervical, vulvar and/or anal lesions, and cervical lesions are eligible for conservative treatment (cohort 2). -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. -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. The following conditions ARE NOT CONSIDERED EXCLUSION CRITERIA. Therefore, candidates complying with them ARE ELIGIBLE FOR INCLUSION in the study: -History of cervical surgery. -History of condyloma acuminata. -History of HIV or other immunosuppressive conditions, either acquired or medically induced. -History of transplant immunosuppression. -History of an autoimmune disease. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 69 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Medical Conditions -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. -Have a fever (defined as temperature =37.8°C) within the 24-hour period prior to the Day 1 visit*. -Have a history of severe allergic reaction (e.g., swelling of the mouth and throat, difficultybreathing, 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 anallergic 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. -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. -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. -Are pregnant at the time of signing informed consent, are planning to be within the full duration of the study or become pregnant during the study period. *For items denoted with an asterisk, if the exclusion criterion is met, then the Day 1 visit may be rescheduled for a time when the criterion is not met. Prior/Concomitant Therapy -Have previously received any HPV vaccine. -Have received within the 3 months prior to the Day 1 vaccination, are receiving, or plan to receive during Day 1 through Month 7 of the study, any immune globulin product (including RhoGAM™ [Ortho-Clinical Diagnostics]) or blood-derived product other than IVIG. -Have received inactivated or recombinant vaccines within 14 days prior to Day 1 vaccination, or live vaccines within 21 days prior to Day 1 vaccination*. Prior/Concurrent Clinical Study Experience -Are concurrently enrolled in other clinical studies of investigational agents. Sexual Activity -Have engaged in sexual activity 48 hours prior to Day 1 (this may result in the detection of viral DNA that has been deposited in the oral cavity and is not the result of ongoing infection) * Sexual activity is defined as: - Penile penetrative vaginal intercourse. - Penile penetrative anal intercourse. - Oral sex involving any contact between subject’s mouth with a partner’s genital or anal area. *: For items denoted with an asterisk, if the exclusion criterion is met, then the Day 1 visit may be reschedu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that vaccination with a 3-dose regimen of 9vHPV will reduce viral infectivity in cervical, anal and oral samples from positivas para VPH16/18/16+18.;Secondary Objective: -To determine HPV antibody levels before and after vaccination (GMT and seroconversion percentages) for each of the 9vHPV-covered HPV types (6, 11, 16, 18, 31, 33, 45, 52, and 58) -Tertiary/Exploratory Objective. To demonstrate viral infectivity reduction in cervical, oral and anal samples from HPV 16/18/16+18-positive women before and after vaccination with 1-dose or 2-dose regimen of 9vHPV.;Primary end point(s): -In-vitro infectivity evaluation (by expression of E1^E4 HPV biomarker in HaCaT keratinocytes) of cervical, anal, 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 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 except 16 and 18 in samples from RIFT-HPV1 study cohort. This endpoint will allow to associate 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 HPV28) in cervical, anal 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.;Timepoint(s) of evaluation of this end point: 7 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -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 except 16 and 18, in samples from RIFT-HPV 1 study cohort.;Timepoint(s) of evaluation of this end point: 7 months | — |
Countries
Spain
Contacts
Public ContactClinical Research and Clinical Tria
UICEC IDIBELL
Outcome results
None listed