PRIMAVERA*-ESCUDDO Trial to Compare One Dose of Bivalent HPV Vaccine to Three Doses of Quadrivalent Vaccine
Human papillomavirus (HPV) vaccination successfully prevents targeted HPV infections, related precancerous lesions, and ultimately has the potential to substantially reduce cervical and other HPV-related cancers. Despite the established efficacy and safety of the HPV vaccine, most girls living in areas with the greatest risk for cervical cancer are not being vaccinated. The cost and logistical difficulties of the recommended multiple-dose schedule has been a significant impediment to vaccination uptake and the prevention of cervical cancer and its associated mortality.
Potential Public Health Impact
The PRIMAVERA*-ESCUDDO Trial is designed to provide convincing and actionable evidence that a single dose of the HPV vaccine will elicit an immune response sufficient to protect against targeted HPV infections and subsequent neoplasms. A single dose schedule can potentially simplify vaccine delivery and vaccination programs’ costs, which can ultimately ensure that more girls receive the vaccine.
Study Rationale and Background
In the non-randomized extension of the Costa Rica HPV Vaccine trial (CVT), investigators reported long-term protection against HPV16 and HPV18 infections and stable antibody levels among women who received a single dose of the bivalent HPV vaccine more than a decade earlier. These observations raise the possibility that a single dose of HPV vaccine may offer sufficient durable protection and set the basis for two new clinical trials, ESCUDDO (efficacy trial, Clinical trials identifier: NCT03180034) and PRIMAVERA (immunobridging trial).
PRIMAVERA will provide earlier and complementary results to the definitive ESCUDDO study that evaluates the vaccine efficacy for a one-dose regimen against virologic outcomes in ~20,000 girls aged 12 to 16-years, which is underway in Costa Rica.
The PRIMAVERA study is a non-randomized, open-label, clinical trial comparing one dose of the bivalent HPV vaccine (Cervarix®) in girls to three doses of the quadrivalent HPV vaccine (Gardasil®) in women. The trial enrolled 620 girls aged 9-14 years and 620 women aged 18-25 years.
The initial vaccination will be administered at the baseline study visit and participants receive either the first dose of Gardasil® or the single dose of Cervarix®. Women receive the second and third doses of Gardasil® at two and six months following their initial baseline visit.
All participants will have blood collected at the 12-, 24-, and 36-month follow-up visits. For participants in the Cervarix® group, blood will also be collected at a follow-up visit one month after vaccination. Each girl is expected to have five study visits, one for vaccination and four follow-up visits. Each woman is expected to have six study visits, three for vaccination and three for follow-up.
*PRIMAVERA (Puente de Respuesta Inmunológica para Mejorar el Acceso a Vacunas y ERrAdicar el cancer)