Comparing One or Two Doses of the Human Papillomavirus Vaccine for the Prevention of Human Papillomavirus Infection, ESCUDDO Study
- Living in the study area without plans to move outside the country in the next six months
- Able to communicate with study personnel
- Willing to participate in the study and sign the informed assent
- Supported in study participation by at least one of their parents (or guardians), who is willing to sign the informed consent document
- In good health as determined by a medical history (physical exam will be conducted if necessary per the doctor’s criterion)
- They have a diagnosis of an autoimmune, degenerative, or neurological disease without treatment or adequate control; a progressive or severe neurological disease; a genetic immunodeficiency; or any other serious chronic disease without treatment and / or adequate control that, according to the principal investigator or designee, for which vaccination is contraindicated (NOTE: Potential participants with these conditions can be included after consultation with the external medical advisor of the study or with an appropriate specialist
- They are allergic to one of the vaccine components, yeast, or latex
- The clinician determining the eligibility in agreement with principal investigator considers that there is a reason that precludes participation
- They have been vaccinated against HPV
- The girl or her parent/legal guardian does not have an identification document
I. For each vaccine separately, to evaluate non-inferiority of one compared to two vaccination doses in the prevention of new HPV16/18 cervical HPV infections that persist 6+ months in girls ages 12-16 years at vaccination.
II. For each vaccine separately, to evaluate one dose of HPV vaccination compared to no vaccination in the protection against HPV16/18 cervical HPV infections that persist 6+ months in girls ages 12-16 years at vaccination; protection resultant from two HPV vaccine doses compared to no vaccination will also be investigated.
I. For each vaccine separately, to compare immunogenicity via measurement of serum antibodies between girls who received one and two doses of the HPV vaccines.
II. For the nonavalent vaccine, demonstrate non-inferiority of one versus two doses in the prevention of any new vaccine-type HPV infection (i.e., aggregate HPV 16/18/31/33/45/52/58) that persist 6+ months (note: HPV6/11, the noncarcinogenic HPV types responsible for genital warts, will be investigated as an ancillary objective, per item 1, sub-item iv, below).
III. For each vaccine separately, demonstrate non-inferiority of one versus two doses in the prevention of any new carcinogenic HPV cervical infection (vaccine and/or non-vaccine types) that persists 6+ months.
IV. Conduct a cost and cost-effectiveness evaluation of HPV vaccination with one versus two doses of the nonavalent and bivalent vaccines in the setting of Costa Rica.
I. For each vaccine separately, demonstrate non-inferiority of one versus two doses in the prevention of study endpoints (including but not limited to those listed below) including a comparison to unvaccinated girls:
Ia. Any new HPV16, HPV18, or HPV16/18 infection (i.e., one-time detection).
IIb. Any new carcinogenic-type HPV infection (i.e., one-time HPV detection of aggregate HPV vaccine and/or non-vaccine HPV types).
Ic. Any new vaccine-type HPV infection (i.e., aggregate HPV 16/18/31/33/45/52/58).
Id. Any new HPV6/11 infection (i.e., one-time detection).
II. Compare HPV attack rate and immunogenicity of Merck nonavalent versus (vs.) GlaxoSmithKline (GSK) bivalent vaccines with respect to number of vaccine doses received in the prevention of six-month persistent HPV16/18 and any carcinogenic infections, and in the prevention of one-time detection of these types.
III. Conditional on demonstrating inferiority of one versus two doses of the vaccine:
IIIa. To evaluate inferiority of one versus two doses.
IIIb. To evaluate reduction in the HPV attack rate of one and two doses compared to none by time (years 1 through 4).
IV. Obtain participants authorization to passively track cervical pre-cancer, carcinoma in situ and cervical cancer outcomes through the national tumor registry, national cytology laboratory, social security registries, national cytology laboratory, and other resources after the trial ends (i.e., to continue indefinitely or until consent is rescinded).
V. Establish a biobank including blood components (for example but not limited to serum, red blood cells, plasma, peripheral blood mononuclear cells), urine, oral and cervical swab samples collected from girls in the randomized trial and the epidemiologic HPV survey for futures analysis related to HPV infection, associated diseases, and effects of the vaccine.
OUTLINE: There are two components to the study: (1) a controlled, randomized, double-blinded non-inferiority clinical trial to compare one-dose to two-dose vaccination among twenty thousand girls 12 to 16 years old; and (2) a concurrent epidemiologic survey for HPV status among four thousand unvaccinated women 17-20 years old. Trial participants are randomized to 1 of 4 arms. Survey participants are assigned to Arm V.
ARM I: Participants receive recombinant human papillomavirus nonavalent vaccine (Gardasil) intramuscularly (IM) at month 0 and diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine adsorbed (DTaP) IM at month 6.
ARM II: Participants receive recombinant human papillomavirus bivalent vaccine (Cervarix) IM at month 0 and DTaP IM at month 6.
ARM III: Participants receive Gardasil IM at month 0 and 6.
ARM IV: Participants receive Cervarix IM at month 0 and 6.
After completion of study intervention, trial participants are followed up every 6 months for up to 4 years.
ARM V: A concurrent epidemiologic survey for HPV status among unvaccinated women. Survey participants are followed for two study visits six months apart to determine their HPV DNA status, with no further follow-up. These women will be offered HPV vaccination (Cervarix) at the two study visits.
Trial Phase Phase IV
Trial Type Prevention
National Cancer Institute
Aimee R. Kreimer
- Primary ID 17-C-N108
- Secondary IDs NCI-2020-08550, 999917108
- Clinicaltrials.gov ID NCT03180034