Single Dose of Cervarix Vaccine in Girls or Three Doses of Gardasil Vaccine in Women for the Prevention of Human Papillomavirus Infection, the PRIMAVERA-ESCUDDO Trial

Study Overview
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Brief Summary
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This phase IIIb trial compares a single dose of the Cervarix vaccine in girls to 3 doses of the Gardasil vaccine in young women for the prevention of human papillomavirus (HPV) infection. Cervarix is a vaccine used to prevent cervical cancer caused by HPV types 16 and 18. Gardasil is vaccine used to prevent cervical, vulvar, and vaginal cancer caused by HPV types 16 and 18 and genital warts caused by HPV types 6 and 11. Giving only one dose of the Cervarix vaccine in girls may work the same as 3 doses of the Gardasil vaccine in young women in preventing HPV infection and ultimately, cervical and other HPV-related cancers. Currently, many women around the world cannot get HPV vaccines because they are too expensive. If this trial can show one dose given to young girls is enough to prevent cancer, more girls might be able to get the vaccine.

Detailed Description
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PRIMARY OBJECTIVE: I. To demonstrate that the immunogenicity (as determined by enzyme-linked immunosorbent assay [ELISA]) of a single dose of recombinant human papillomavirus bivalent vaccine (Cervarix) in 9-14 year old girls is non-inferior to the immunogenicity of three doses of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine (Gardasil), administered at 0, 2, and 6 months, in 18-25 year old women 36 months after initial vaccination, with an interim analysis at 24 months after initial vaccination. SECONDARY OBJECTIVES: I. To compare the distribution of HPV -16 and HPV-18 antibodies levels, assessed at 24 and 36 months after initial vaccination, following a single dose of Cervarix in 9-14 year old girls and three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25 year old women. II. To compare rates of seroconversion based on HPV-16 and HPV-18 antibody levels, assessed at 24 and 36 months after initial vaccination, following a single dose of Cervarix in 9-14 year old girls and three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25 year old women. III. To compare geometric mean titers (GMTs), distributions, and seroconversion rates for HPV-16 and HPV-18 antibodies, assessed at 24 and 36 months after initial vaccination, following a single dose of Cervarix in 9-11 year old girls and three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25 year old women; to perform a similar comparison restricting to 12-14 year old girls. IV. To compare GMTs, distributions, and seroconversion rates for HPV-16 and HPV-18 antibodies, assessed at 1-month after vaccination and 1-year after vaccination, following a single dose of Cervarix in 9-10 year old girls and a single dose of Cervarix in 11-14 year old girls. V. To evaluate whether baseline variables (e.g. geographic district, initial antibody levels, date of vaccination) are associated with GMTs, distributions, and seroconversion rates for HPV16 and HPV-18 antibodies, assessed at 24 and 36 months after initial vaccination. OUTLINE: Participants are assigned to 1 of 2 groups. GROUP I: Participants 9-14 years old receive Cervarix intramuscularly (IM) at baseline. GROUP II: Participants 18-25 years old receive Gardasil IM at baseline and at 2 and 6 months in the absence of unacceptable toxicity. After completion of trial vaccine dose(s), participants are followed up at 1, 12, 24, and 36 months.

Official Title
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Non-Inferiority Trial Comparing Immunogenicity From 1-Dose of Bivalent HPV Vaccine in Girls to 3-Doses of Quadrivalent Vaccine in Women: The PRIMAVERA-ESCUDDO Trial (Puente de Respuesta Inmunológica Para Mejorar el Acceso a Vacunas y ERrAdicar el Cancer)

Conditions
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Human Papillomavirus-Related Cervical Carcinoma

Intervention / Treatment
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* Biological: Quadrivalent Human Papillomavirus (types 6, 11, 16, 18) Recombinant Vaccine
* Biological: Recombinant Human Papillomavirus Bivalent Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between: 9 and 14 years inclusive for Cervarix group 18 and 25 years inclusive for Gardasil group Living in the study area without plans to move outside the country in the next six months Able to communicate with study personnel Able and willing to provide a blood sample Willing to permit export of blood samples to the United States Willing to participate in the study and: If Cervarix group and less than 12 years old, receive study information and be supported in study participation by at least one of parent (or guardian), who is willing to sign the informed consent document If Cervarix group and 12 years old or older, sign the informed assent and be supported in study participation by at least one parent (or guardian), who is willing to sign the informed consent document If Gardasil group, sign the informed consent In good health as determined by a medical history (physical exam will be conducted if necessary per the doctor's criterion) Exclusion Criteria: 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, including yeast (if Gardasil group) They have received immunoglobulins within 90 days preceding enrollment/vaccination visit They are unwilling to provide a blood sample Unwilling to permit export of blood samples to the United States They have a positive urine pregnancy test result They are pregnant They are planning to become pregnant The clinician determining eligibility in agreement with the principal investigator considers that there is a reason that precludes participation They have been vaccinated against HPV The participant or her parent/legal guardian, as applicable, does not have an identification document

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I (Cervarix)<br>Participants 9-14 years old receive Cervarix IM at baseline. | Biological: Recombinant Human Papillomavirus Bivalent Vaccine<br>* Given IM<br>* Other names: Recombinant HPV Bivalent Vaccine;|
| Active Comparator: Group II (Gardasil)<br>Participants 18-25 years old receive Gardasil IM at baseline and at 2 and 6 months in the absence of unacceptable toxicity. | Biological: Quadrivalent Human Papillomavirus (types 6, 11, 16, 18) Recombinant Vaccine<br>* Given IM<br>* Other names: V501;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Human papillomavirus (HPV) 16 antibody level | Will measure HPV-16 specific serum antibody using the HPV type-specific enzyme-linked immunoassay (ELISA) on serum. Will estimate the two-sided 99% confidence interval of the geometric mean titer (GMT) ratios for HPV-16 and HPV-18 at 24 months and the two-sided 96% confidence intervals of the GMT ratios for HPV-16 and HPV-18 at 36 months. | At 24 months after initial vaccination | 
| HPV-16 antibody level | Will measure HPV-16 specific serum antibody using the HPV type-specific ELISA on serum. Will estimate the two-sided 99% confidence interval of the GMT ratios for HPV-16 and HPV-18 at 24 months and the two-sided 96% confidence intervals of the GMT ratios for HPV-16 and HPV-18 at 36 months. | At 36 months after initial vaccination | 
| HPV-18 antibody level | Will measure HPV-18 specific serum antibody using the HPV type-specific ELISA on serum. Will estimate the two-sided 99% confidence interval of the GMT ratios for HPV-16 and HPV-18 at 24 months and the two-sided 96% confidence intervals of the GMT ratios for HPV-16 and HPV-18 at 36 months. | At 24 months after initial vaccination | 
| HPV-18 antibody level | Will measure HPV-18 specific serum antibody using the HPV type-specific ELISA on serum. Will estimate the two-sided 99% confidence interval of the GMT ratios for HPV-16 and HPV-18 at 24 months and the two-sided 96% confidence intervals of the GMT ratios for HPV-16 and HPV-18 at 36 months. | At 36 months after initial vaccination |