Human Papillomavirus Infection, Human Papillomavirus-Related Malignant Neoplasm
Conditions
Brief summary
This phase IV trial evaluates the long term protection provided by either one or two doses of the 9v human papillomavirus (HPV) vaccine for participants who were part of the ESCUDDO study.
Detailed description
PRIMARY OBJECTIVES: I. To estimate the Incidence Rate Difference (IRD) and Relative Risk (RR) of incident HPV 6/11/16/18/31/33/45/52/58-related 6-months cervicovaginal persistent infection between recipients of single dose and 2 doses of 9vHPV vaccine, 7 to 10 years following HPV vaccination. II. To estimate the IRD and RR of incident HPV 6/11/16/18/31/33/45/52/58-related 6-months cervicovaginal persistent infection between recipients of single dose and 2 doses of 9vHPV vaccine, 1 to 10 years following HPV vaccination. OUTLINE: This is an interventional study. Participants are assigned to 1 of 3 arms. Arm I (ONE DOSE GARDASIL9): Participants undergo cervicovaginal and anal swab self sample collection, blood sample collection, and complete questionnaires on study. Arm II (TWO DOSE GARDASIL9): Participants undergo cervicovaginal and anal swab self sample collection, blood sample collection, and complete questionnaires on study. Arm III (UNVACCINATED): Participants undergo cervicovaginal and anal swab self sample collection, blood sample collection, and complete questionnaires on study. These women will be offered HPV vaccination (Gardasil9). Trial participants with documented persistent type-specific HPV infections will be triaged to colposcopy and may undergo biopsy collection and treatment.
Interventions
Given IM in ESCUDDO (NCT03180034)
Given intramuscularly (IM) in ESCUDDO (NCT03180034)
Sponsors
National Cancer Institute (NCI)
Merck Sharp and Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Masking description
Specimen lab
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* TRIAL PARTICIPANTS: Participation in ESCUDDO base study * TRIAL PARTICIPANTS: Randomization (excluding the two participants who had major protocol deviations in the ESCUDDO base study) to the Gardasil9 1- and 2-dose arms * TRIAL PARTICIPANTS: A signed informed consent form for ESCUDDO LTFU * TRIAL PARTICIPANTS: Opportunity to complete three total study visits * LTFU SURVEY GROUP: We will match the current ages of ESCUDDO LTFU trial participants when they attend their 9.5-year study visit (21 to 26 years of age)
Exclusion criteria
* TRIAL PARTICIPANTS: Enrollment cannot occur beyond her 10 year study visit * LTFU SURVEY GROUP: They report they are pregnant * LTFU SURVEY GROUP: They report being vaccinated against HPV * LTFU SURVEY GROUP: The qualified healthcare personnel determining eligibility, in agreement with principal investigator, considers a reason that precludes participation; or * LTFU SURVEY GROUP: They do not have an identification document
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of incident persistent human papillomavirs (HPV) infection related to vaccine types observed during long-term follow-up study (LFTU) and the combined ESCUDDO base and LTFU studies; in recipients of single dose and 2 doses of the 9vHPV vaccine | 7 to 10 years after first HPV vaccination | Estimate the incidence rate difference and relative risk of first type-specific 6 month cervicovaginal persistent infection related to any of the nine vaccine HPV types (HPV 6/11/16/18/31/33/45/52/58) between recipients of 1 dose and 2 doses of Gardasil9. Study measures include self-collected cervicovaginal swabs collected every 6 months, HPV genotyping using the TypeSeq2 assay, identification of type-specific persistent infection based on two positive samples collected ≥3 months apart, and calculation of incidence rates in the Per-Protocol Efficacy (PPE) population. |
| Comparison of cumulative persistent HPV infection (Base Study + LTFU) | 1 to 10 years after first HPV vaccination | Estimate the incidence rate difference and relative risk of first any-type 6 month cervicovaginal persistent infection related to any of the nine vaccine HPV types (HPV 6/11/16/18/31/33/45/52/58) between recipients of 1 dose versus 2 doses of Gardasil9 over the combined study period. Study measures include serial self-collected cervicovaginal swabs obtained from Year 1 through Year 10, HPV testing using the TypeSeq2 assay, determination of persistent infection from repeated HPV-positive results, and longitudinal follow-up to capture first occurrence of infection with any vaccine HPV type. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vaccine efficacy against multiple cervical endpoints, anal HPV prevalence, immunogenicity, and histologic endpoints | 9.5 to 10 years after first HPV vaccination | Estimate the vaccine efficacy of 1 dose and 2 doses of Gardasil9 against 6 month cervicovaginal persistent infection related to HPV 6/11/16/18/31/33/45/52/58 by comparing vaccinated participants with an unvaccinated epidemiology survey cohort. Study measures include self-collected cervicovaginal samples obtained at the 9.5- and 10-year visits, HPV genotyping using the TypeSeq2 assay, identification of persistent infections present at both visits, and comparison of infection prevalence in vaccinated participants versus approximately 4,000 unvaccinated women enrolled in the Epidemiologic HPV Survey. |
| Comparison of high-grade cervical disease | 7 to 10 years after first HPV vaccination | Estimate the incidence rate difference and relative risk of HPV 16/18/31/33/45/52/58-related high-grade cervical disease (CIN2 or worse) between recipients of 1 dose and 2 doses of Gardasil9. Study measures include HPV screening results from cervicovaginal swabs, referral to cytology and colposcopy through protocol-defined triage algorithms, collection of cervical biopsies and excisional specimens, pathology panel review, and HPV genotyping of tissue specimens to confirm HPV-associated CIN2, CIN3, adenocarcinoma in situ (AIS), or cervical cancer. |
| Long-term immunogenicity assessment | Up to 10 years after vaccination, with measurements during LTFU annual visits | Evaluate the peak and persistence of antibody responses (geometric mean concentrations and seropositivity rates) to all nine vaccine HPV types (HPV 6/11/16/18/31/33/45/52/58) following 1-dose and 2-dose vaccination regimens. Study measures include serum samples collected at enrollment and annual follow-up visits, laboratory assessment of HPV-specific antibody concentrations using the NCI IgG Luminex Immunoassay (LIA), calculation of geometric mean concentrations (GMCs), and determination of seropositivity rates for each vaccine HPV type. Additional annual blood collections in the Immunogenicity Subgroup (ISG) support detailed analyses of immune response durability. The ISG is a subset of approximately 700 Gardasil 9 participants (about 350 per dose arm) from ESCUDDO who consent to continue in the subgroup during LTFU. |
Countries
Costa Rica
Contacts
PRINCIPAL_INVESTIGATORAimee Kreimer
National Cancer Institute (NCI)
Outcome results
None listed