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 (PRIMAVERA)

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")

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.

Study Overview

• Status: Completed
• Conditions: Human Papillomavirus-Related Cervical Carcinoma
• Intervention / Treatment: Biological: Recombinant Human Papillomavirus Bivalent Vaccine; Biological: Quadrivalent Human Papillomavirus (types 6, 11, 16, 18) Recombinant Vaccine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1240
• Phase: Phase 3

Contacts and Locations

Study Locations

• Costa Rica
  • Guanacaste
    • Liberia, Guanacaste, Costa Rica, 50101
      • Agencia Costarricense de Investigaciones Biomédicas (ACIB)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Girls (1D Cervarix®); Participants 9-14 years old receive Cervarix IM at baseline.	Biological: Recombinant Human Papillomavirus Bivalent Vaccine; Given IM; Other Names: Cervarix; GSK-580299; HPV 16/18 L1 VLP/AS04 VAC; HPV-16/18 VLP/AS04 Vaccine; Human Papillomavirus 16/18 L1 Virus-Like Particle/AS04 Vaccine; Human Papillomavirus Bivalent Types 16 and 18 Vaccine, Recombinant; Human Papillomavirus Vaccine L1 16,18; Human Papillomavirus Vaccine, L1 Type 16, 18; Recombinant HPV Bivalent Vaccine
Active Comparator: Women (3D Gardasil-4®); 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; Given IM; Other Names: Gardasil; V501; Quadrivalent HPV [Type 6, 11, 16 and 18] L1 Virus-Like Particle vaccine; quadrivalent human papillomavirus (types 6, 11, 16, and 18) recombinant vaccine; Recombinant Human Papillomavirus (HPV) Quadrivalent Vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number Seropositive for HPV16 at 36 Months	Will measure HPV16 specific serum antibody using the HPV type-specific ELISA on serum. For computing proportions seropositive and proportions seroconverting, HPV16 is seropositive if the ELISA concentration is greater than 1.41 IU/mL. Participants whose analysis of the 36-month sample does not generate a valid HPV16 result will be excluded only from the 36-month HPV16 analysis.	36 months following initial HPV vaccination
Immunogenicity for HPV16 of One Dose of Bivalent HPV Vaccine (Cervarix) in 9-14 Year Old Girls Compared to Three Doses of Quadrivalent HPV Vaccine (Gardasil), Administered at 0,2 and 6 Months, in 18-25 Year Old Women, 36 Months After Initial Vaccination	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.	36 months following initial vaccination
Number Seropositive for HPV18 at 36 Months	Will measure HPV18 specific serum antibody using the HPV type-specific ELISA on serum. For computing proportions seropositive and proportions seroconverting, HPV18 is seropositive if the ELISA concentration is greater than 1.05 IU/mL. Participants whose analysis of the 36-month sample does not generate a valid HPV18 result will be excluded only from the 36-month HPV18 analysis.	36 months following initial vaccination
Immunogenicity for HPV18 of One Dose of Bivalent HPV Vaccine (Cervarix) in 9-14 Year Old Girls Compared to Three Doses of Quadrivalent HPV Vaccine (Gardasil), Administered at 0,2, and 6 Months, in 18-25 Year Old Women, 36 Months After Initial Vaccination	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.	36 months following initial vaccination
Number Seropositive for HPV16 at 24 Months	Will measure HPV16 specific serum antibody using the HPV type-specific ELISA on serum. For computing proportions seropositive and proportions seroconverting, HPV16 is seropositive if the ELISA titer is greater than 1.41 IU/mL. Participants whose analysis of the 24-month sample does not generate a valid HPV16 result will be excluded only from the 24-month HPV16 analysis.	24 months following initial HPV vaccination
Immunogenicity for HPV16 of One Dose of Bivalent HPV Vaccine (Cervarix) in 9-14 Year Old Girls Compared to Three Doses of Quadrivalent HPV Vaccine (Gardasil), Administered at 0,2, and 6 Months, in 18-25 Year Old Women, 24 Months After Initial Vaccination	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 concentration (GMC) ratio for HPV-16 at 24 months	24 months following initial vaccination
Number Seropositive for HPV18 at 24 Months	Will measure HPV18 specific serum antibody using the HPV type-specific ELISA on serum. For computing proportions seropositive and proportions seroconverting, HPV18 is seropositive if the ELISA titer is greater than 1.05 IU/mL. Participants whose analysis of the 24-month sample does not generate a valid HPV18 result will be excluded only from the 24-month HPV18 analysis.	24 months following initial vaccination
Immunogenicity for HPV18 of One Dose of Bivalent HPV Vaccine (Cervarix) in 9-14 Year Old Girls Compared to Three Doses of Quadrivalent HPV Vaccine (Gardasil), Administered at 0,2, and 6 Months, in 18-25 Year Old Women, 24 Months After Initial Vaccination	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 Geometric Mean Concentration (GMC) ratio for HPV-18 at 24 months.	24 months following initial vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of Proportions With Seroconversion Based on HPV16 Antibody Levels Assessed at 36 Months	To compare proportions with seroconversion based on HPV16 antibody levels, assessed at 36 months after initial vaccination, following a single dose of Cervarix in 9-14 year old girls and following three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25 year old women.	36 months
Comparison of Proportions With Seroconversion Based on HPV18 Antibody Levels Assessed at 36 Months	To compare proportions with seroconversion based on HPV18 antibody levels, assessed at 36 months after initial vaccination, following a single dose of Cervarix in 9-14 year old girls and following three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25 year old women.	36 month
Comparison of Proportions With Seroconversion Based HPV16 Antibody Levels at 24 Months	To compare proportions with seroconversion based on HPV16 antibody levels, assessed at 24 months after initial vaccination, following a single dose of Cervarix in 9-14 year old girls and following three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25 year old women.	24 months
Comparison of Proportions With Seroconversion Based on HPV18 Antibody Levels Assessed at 24 Months	To compare proportions with seroconversion based on HPV18 antibody levels, assessed at 24 months after initial vaccination, following a single dose of Cervarix in 9-14 year old girls and following three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25 year old women.	24 months
Comparison of Distribution of HPV16 Antibodies Levels Assessed at 36 Months	Distribution of HPV16 antibodies levels assessed at 36 months following a single dose of Cervarix in 9-14 year old girls compared to distribution of HPV16 antibodies levels assessed at 36 months following three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25 year old women. Shown as medians and ranges by deciles.	36 months following initial vaccination
Comparison of Distribution of HPV18 Antibodies Levels Assessed at 36 Months	Distribution of HPV18 antibodies levels assessed at 36 months following a single dose of Cervarix in 9-14 year old girls compared to distribution of HPV18 antibodies levels assessed at 36 months following three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25 year old women. Shown in medians and ranges by deciles.	36 months
Comparison of Distribution of HPV16 Antibodies Levels Assessed at 24 Months	Distribution of HPV16 antibodies levels assessed at 24 months following a single dose of Cervarix in 9-14 year old girls compared to distribution of HPV16 antibodies levels assessed at 24 months following three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25 year old women. Shown as medians and ranges by deciles.	24 months
Comparison of Distribution of HPV18 Antibodies Levels Assessed at 24 Months	Distribution of HPV18 antibodies levels assessed at 24 months following a single dose of Cervarix in 9-14 year old girls compared to distribution of HPV18 antibodies levels assessed at 24 months following three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25 year old women. Shown as medians and ranges by deciles.	24 months
Number Seropositive for HPV16 at 36 Months, Excluding 9-10 Year Olds	Will measure HPV16 specific serum antibody using the HPV type-specific ELISA on serum. assessed at 36 months after initial vaccination, following a single dose of Cervarix in 11-14-year-old girls and three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25 year old women. For computing proportions seropositive and proportions seroconverting, HPV16 is seropositive if the ELISA concentration is greater than 1.41 IU/mL. Participants whose analysis of the 36-month sample does not generate a valid HPV16 result will be excluded only from the 36-month HPV16 analysis.	36 month
Comparison of GMCs for HPV16 Antibodies Assessed at 36 Months, Excluding 9-10-year-old Girls	To compare GMCs for HPV16 antibodies, assessed at 36 months after initial vaccination, following a single dose of Cervarix in 11-14-year-old girls and three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25 year old women.	36 month
Comparison of Seroconversion Proportions for HPV16 Antibodies Assessed at 36 Months, Excluding 9-10-year-old Girls	To compare seroconversion proportions for HPV16 antibodies, assessed at 36 months after initial vaccination, following a single dose of Cervarix in 11-14-year-old girls and three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25 year old women.	36 month
Number Seropositive for HPV18 at 36 Months, Excluding 9-10 Year Olds	Will measure HPV18 specific serum antibody using the HPV type-specific ELISA on serum. assessed at 36 months after initial vaccination, following a single dose of Cervarix in 11-14-year-old girls and three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25 year old women. For computing proportions seropositive and proportions seroconverting, HPV18 is seropositive if the ELISA concentration is greater than 1.05 IU/mL. Participants whose analysis of the 36-month sample does not generate a valid HPV18 result will be excluded only from the 36-month HPV18 analysis.	36 month
Comparison of GMCs for HPV18 Antibodies, Assessed at 36 Months, Excluding 9-10-year-old Girls	To compare GMCs for HPV18 antibodies, assessed at 36 months after initial vaccination, following a single dose of Cervarix in 11-14-year-old girls and three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25-year-old women.	36 month
Comparison of Seroconversion Proportions for HPV18 Antibodies, Assessed at 36 Months, Excluding 9-10-year-old Girls	To compare seroconversion proportions for HPV18 antibodies, assessed at 36 months after initial vaccination, following a single dose of Cervarix in 11-14-year-old girls and three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25-year-old women.	36 month
Number Seropositive for HPV16 at 24 Months, Excluding 9-10 Year Olds	Will measure HPV16 specific serum antibody using the HPV type-specific ELISA on serum. assessed at 24 months after initial vaccination, following a single dose of Cervarix in 11-14-year-old girls and three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25 year old women. For computing proportions seropositive and proportions seroconverting, HPV16 is seropositive if the ELISA concentration is greater than 1.41 IU/mL. Participants whose analysis of the 24-month sample does not generate a valid HPV16 result will be excluded only from the 24-month HPV16 analysis.	24 month
Comparison of GMCs for HPV16 Assessed at 24 Months, Excluding 9-10-year-old Girls	To compare GMCs for HPV16 antibodies, assessed at 24 months after initial vaccination, following a single dose of Cervarix in 11-14-year-old girls and three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25-year-old women.	24 months
Comparison of Seroconversion Proportions for HPV16 Assessed at 24 Months, Excluding 9-10-year-old Girls	To compare seroconversion proportions for HPV16 antibodies, assessed at 24 months after initial vaccination, following a single dose of Cervarix in 11-14-year-old girls and three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25-year-old women.	24 months
Number Seropositive for HPV18 at 24 Months, Excluding 9-10 Year Olds	Will measure HPV18 specific serum antibody using the HPV type-specific ELISA on serum. assessed at 24 months after initial vaccination, following a single dose of Cervarix in 11-14-year-old girls and three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25 year old women. For computing proportions seropositive and proportions seroconverting, HPV18 is seropositive if the ELISA concentration is greater than 1.05 IU/mL. Participants whose analysis of the 24-month sample does not generate a valid HPV18 result will be excluded only from the 24-month HPV18 analysis.	24 month
Comparison of GMCs for HPV18 Antibodies, Assessed at 24 Months, Excluding 9-10-year-old Girls	To compare GMCs for HPV18 antibodies, assessed at 24 months after initial vaccination, following a single dose of Cervarix in 11-14-year-old girls and three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25-year-old women.	24 months
Comparison of Seroconversion Proportions for HPV18 Antibodies, Assessed at 24 Months, Excluding 9-10-year-old Girls	To compare seroconversion proportions for HPV18 antibodies, assessed at 24 months after initial vaccination, following a single dose of Cervarix in 11-14-year-old girls and three doses of Gardasil, administered at 0, 2, and 6 months, in 18-25-year-old women.	24 months
Number Seropositive for HPV16 Antibodies, Assessed at 1 Month After Vaccination, in Younger and Older Girls	Will measure HPV16 specific serum antibody using the HPV type-specific ELISA on serum. For computing proportions seropositive and proportions seroconverting, HPV16 is seropositive if the ELISA titer is greater than 1.41 IU/mL. Participants whose analysis of the 1-month sample does not generate a valid HPV16 result will be excluded only from the 1-month HPV16 analysis.	1 month
Comparison of GMCs for HPV16 Antibodies, Assessed at 1 Month After Vaccination in Younger and Older Girls	To compare GMCs for HPV16 antibodies, assessed at 1 month after vaccination, following a single dose of Cervarix in 9-10-year-old girls and following a single dose of Cervarix in 11-14-year-old girls, in order to compare girls who were in and not in the age range for routine HPV vaccination in Costa Rica.	1 month
Comparison of Seroconversion Proportions for HPV16 Antibodies, Assessed at 1 Month After Vaccination in Younger and Older Girls	To compare seroconversion proportions for HPV16 antibodies, assessed at 1 month after vaccination, following a single dose of Cervarix in 9-10-year-old girls and following a single dose of Cervarix in 11-14-year-old girls.	1 month
Number Seropositive for HPV18 Antibodies, Assessed at 1 Month After Vaccination, in Younger and Older Girls	Will measure HPV18 specific serum antibody using the HPV type-specific ELISA on serum. For computing proportions seropositive and proportions seroconverting, HPV18 is seropositive if the ELISA titer is greater than 1.05 IU/mL. Participants whose analysis of the 1-month sample does not generate a valid HPV18 result will be excluded only from the 1-month HPV18 analysis.	1 month
Comparison of GMCs for HPV18 Antibodies, Assessed at 1 Month After Vaccination in Younger and Older Girls	To compare seroconversion proportions for HPV18 antibodies, assessed at 1 month after vaccination, following a single dose of Cervarix in 9-10-year-old girls and following a single dose of Cervarix in 11-14-year-old girls, in order to compare girls who were in and not in the age range for routine HPV vaccination in Costa Rica.	1 month
Comparison of Seroconversion Proportions for HPV18 Antibodies, Assessed at 1 Month After Vaccination in Younger and Older Girls	To compare seroconversion proportions for HPV18 antibodies, assessed at 1 month after vaccination, following a single dose of Cervarix in 9-10-year-old girls and following a single dose of Cervarix in 11-14-year-old girls, in order to compare girls who were in and not in the age range for routine HPV vaccination in Costa Rica.	1 month
Number Seropositive for HPV16 Antibodies, Assessed at 12 Months After Vaccination, in Younger and Older Girls	Will measure HPV16 specific serum antibody using the HPV type-specific ELISA on serum. For computing proportions seropositive and proportions seroconverting, HPV16 is seropositive if the ELISA titer is greater than 1.41 IU/mL. Participants whose analysis of the 12-month sample does not generate a valid HPV16 result will be excluded only from the 12-month HPV16 analysis.	12 months
Comparison of GMCs for HPV16 Antibodies, Assessed at 12 Months After Vaccination in Younger and Older Girls	To compare GMCs for HPV16 antibodies, assessed at 12 months after vaccination, following a single dose of Cervarix in 9-10-year-old girls and following a single dose of Cervarix in 11-14-year-old girls, in order to compare girls who were in and not in the age range for routine HPV vaccination in Costa Rica.	1 year
Comparison of Seroconversion Proportions for HPV16 Antibodies, Assessed at 12 Months After Vaccination in Younger and Older Girls	To compare seroconversion proportions for HPV16 antibodies, assessed at 12 months after vaccination, following a single dose of Cervarix in 9-10-year-old girls and following a single dose of Cervarix in 11-14-year-old girls.	1 year
Number Seropositive for HPV18 Antibodies, Assessed at 12 Months After Vaccination, in Younger and Older Girls	Will measure HPV18 specific serum antibody using the HPV type-specific ELISA on serum. For computing proportions seropositive and proportions seroconverting, HPV18 is seropositive if the ELISA titer is greater than 1.05 IU/mL. Participants whose analysis of the 12-month sample does not generate a valid HPV18 result will be excluded only from the 12-month HPV18 analysis.	12 month
Comparison of GMCs for HPV18 Antibodies, Assessed at 12 Months After Vaccination in Younger and Older Girls	To compare GMCs for HPV18 antibodies, assessed at 12 months after vaccination, following a single dose of Cervarix in 9-10-year-old girls and following a single dose of Cervarix in 11-14-year-old girls. in order to compare girls who were in and not in the age range for routine HPV vaccination in Costa Rica.	12 months
Comparison of Seroconversion Proportions for HPV18 Antibodies, Assessed at 12 Months After Vaccination, in Younger and Older Girls	To compare seroconversion proportions for HPV18 antibodies, assessed at 1 year after vaccination, following a single dose of Cervarix in 9-10-year-old girls and following a single dose of Cervarix in 11-14-year-old girls, in order to compare girls who were in and not in the age range for routine HPV vaccination in Costa Rica.	1 year
Number Seropositive for HPV16 at 36 Months, By Enrollment Age Group	Will measure HPV16 specific serum antibody using the HPV type-specific ELISA on serum. For computing proportions seropositive and proportions seroconverting, HPV16 is seropositive if the ELISA titer is greater than 1.41 IU/mL. Participants whose analysis of the 36-month sample does not generate a valid HPV16 result will be excluded only from the 36-month HPV16 analysis.	36 months
Comparison of GMCs for HPV16 Antibodies Assessed at 36 Months, by Enrollment Age Group	To evaluate whether age is associated with GMCs for HPV16 antibodies, assessed at 36 months after initial vaccination.	36 month
Comparison of Seroconversion Proportions for HPV16, Assessed at 36 Months, by Enrollment Age Group	To evaluate whether age is associated with seroconversion proportions for HPV-16 antibodies, assessed at 36 months after initial vaccination.	36 month
Number Seropositive for HPV18 at 36 Months, By Enrollment Age Group	Will measure HPV18 specific serum antibody using the HPV type-specific ELISA on serum. For computing proportions seropositive and proportions seroconverting, HPV18 is seropositive if the ELISA titer is greater than 1.05 IU/mL. Participants whose analysis of the 36-month sample does not generate a valid HPV18 result will be excluded only from the 36-month HPV18 analysis.	36 months
Comparison of GMCs for HPV18 Antibodies, Assessed at 36 Months, by Enrollment Age Group	To evaluate whether age is associated with GMCs for HPV18 antibodies, assessed at 36 months after initial vaccination.	36 month
Comparison of Seroconversion Proportions for HPV18, Assessed at 36 Months, by Enrollment Age Group	To evaluate whether age is associated with seroconversion proportions for HPV-16 antibodies, assessed at 36 months after initial vaccination.	36 month
Number Seropositive for HPV16 at 24 Months, By Enrollment Age Group	Will measure HPV16 specific serum antibody using the HPV type-specific ELISA on serum. For computing proportions seropositive and proportions seroconverting, HPV16 is seropositive if the ELISA titer is greater than 1.41 IU/mL. Participants whose analysis of the 24-month sample does not generate a valid HPV16 result will be excluded only from the 24-month HPV16 analysis.	36 months
Comparison of GMCs for HPV16 Antibodies Assessed at 24 Months, by Enrollment Age Group	To evaluate whether age is associated with GMCs for HPV16 antibodies, assessed at 24 months after initial vaccination.	24 month
Comparison of Seroconversion Proportions for HPV16, Assessed at 24 Months, by Enrollment Age Group	To evaluate whether age is associated with seroconversion proportions for HPV-16 antibodies, assessed at 24 months after initial vaccination.	24 month
Number Seropositive for HPV18 at 24 Months, By Enrollment Age Group	Will measure HPV18 specific serum antibody using the HPV type-specific ELISA on serum. For computing proportions seropositive and proportions seroconverting, HPV18 is seropositive if the ELISA titer is greater than 1.05 IU/mL. Participants whose analysis of the 24-month sample does not generate a valid HPV18 result will be excluded only from the 24-month HPV18 analysis.	24 months
Comparison of GMCs for HPV18 Antibodies, Assessed at 24 Months, by Enrollment Age Group	To evaluate whether age is associated with GMCs for HPV18 antibodies, assessed at 24 months after initial vaccination.	24 month
Comparison of Seroconversion Proportions for HPV18, Assessed at 24 Months, by Enrollment Age Group	To evaluate whether age is associated with seroconversion proportions for HPV-16 antibodies, assessed at 24 months after initial vaccination.	24 month
Number Seropositive for HPV16, Assessed at 36 Months, by Enrollment Month Group	HPV16 ELISA results at 36-months (final analysis) by arm in according to protocol (ATP) analytical cohort, stratified by enrollment month	36 month
Comparison of GMCs for HPV16 Antibodies Assessed at 36 Months, by Enrollment Month Group	HPV16 ELISA results at 36-months (final analysis) by arm in according to protocol (ATP) analytical cohort, stratified by enrollment month	36 month
Comparison of Seroconversion Proportions for HPV16, Assessed at 36 Months, by Enrollment Month	HPV16 ELISA results at 36-months (final analysis) by arm in according to protocol (ATP) analytical cohort, stratified by enrollment month	36 month
Number Seropositive for HPV18, Assessed at 36 Months, by Enrollment Month Group	HPV18 ELISA results at 36-months (final analysis) by arm in according to protocol (ATP) analytical cohort, stratified by enrollment month	36 month
Comparison of GMCs for HPV18 Antibodies, Assessed at 36 Months, by Enrollment Month Group	HPV18 ELISA results at 36-months (final analysis) by arm in according to protocol (ATP) analytical cohort, stratified by enrollment month	36 month
Comparison of Seroconversion Proportions for HPV18, Assessed at 36 Months, by Enrollment Month	HPV18 ELISA results at 36-months (final analysis) by arm in according to protocol (ATP) analytical cohort, stratified by enrollment month	36 month
Number Seropositive for HPV16, Assessed at 24 Months, by Enrollment Month	HPV16 ELISA results at 24-months (interim analysis) by arm in according to protocol (ATP) analytical cohort, stratified by enrollment month	24 month
Comparison of GMCs for HPV16 Antibodies Assessed at 24 Months, by Enrollment Month Group	HPV16 ELISA results at 24-months (interim analysis) by arm in according to protocol (ATP) analytical cohort, stratified by enrollment month	24 month
Comparison of Seroconversion Proportions for HPV16, Assessed at 24 Months, by Enrollment Month	HPV16 ELISA results at 24-months (interim analysis) by arm in according to protocol (ATP) analytical cohort, stratified by enrollment month	24 month
Number Seropositive for HPV18, Assessed at 24 Months, by Enrollment Month Group	HPV18 ELISA results at 24-months (interim analysis) by arm in according to protocol (ATP) analytical cohort, stratified by enrollment month	24 month
Comparison of GMCs for HPV18 Antibodies Assessed at 24 Months, by Enrollment Month Group	HPV18 ELISA results at 24-months (interim analysis) by arm in according to protocol (ATP) analytical cohort, stratified by enrollment month	24 month
Comparison of Seroconversion Proportions for HPV18, Assessed at 24 Months, by Enrollment Month	HPV18 ELISA results at 24-months (interim analysis) by arm in according to protocol (ATP) analytical cohort, stratified by enrollment month	24 month
Number Seropositive for HPV16, Assessed at 36 Months, by Enrollment District	HPV16 ELISA results at 36-months (final analysis) by arm in the according to protocol analytical cohort stratified by enrollment region.	36 month
Comparison of GMCs for HPV16 Antibodies, Assessed at 36 Months, by Enrollment District	HPV16 ELISA results at 36-months (final analysis) by arm in the according to protocol analytical cohort stratified by enrollment region.	36 month
Comparison of Seroconversion Proportions for HPV16, Assessed at 36 Months, by Enrollment District	HPV16 ELISA results at 36-months (final analysis) by arm in the according to protocol analytical cohort stratified by enrollment region.	36 month
Number Seropositive for HPV18, Assessed at 36 Months, by Enrollment District	HPV18 ELISA results at 36-months (final analysis) by arm in the according to protocol analytical cohort stratified by enrollment region.	36 month
Comparison of GMCs for HPV18 Antibodies, Assessed at 36 Months, by Enrollment District	HPV18 ELISA results at 36-months (final analysis) by arm in the according to protocol analytical cohort stratified by enrollment region.	36 month
Comparison of Seroconversion Proportions for HPV18, Assessed at 36 Months, by Enrollment District	HPV18 ELISA results at 36-months (final analysis) by arm in the according to protocol analytical cohort stratified by enrollment region.	36 month
Number Seropositive for HPV16, Assessed at 24 Months, by Enrollment District	HPV16 ELISA results at 24-months (interim analysis) by arm in the according to protocol analytical cohort stratified by enrollment region.	24 month
Comparison of GMCs for HPV16 Antibodies, Assessed at 24 Months, by Enrollment District	HPV16 ELISA results at 24-months (interim analysis) by arm in the according to protocol analytical cohort stratified by enrollment region.	24 month
Comparison of Seroconversion Proportions for HPV16, Assessed at 24 Months, by Enrollment District	HPV16 ELISA results at 24-months (interim analysis) by arm in the according to protocol analytical cohort stratified by enrollment region.	24 month
Number Seropositive for HPV18, Assessed at 24 Months, by Enrollment District	HPV18 ELISA results at 24-months (interim analysis) by arm in the according to protocol analytical cohort stratified by enrollment region.	24 month
Comparison of GMCs for HPV18 Antibodies, Assessed at 24 Months, by Enrollment District	HPV18 ELISA results at 24-months (interim analysis) by arm in the according to protocol analytical cohort stratified by enrollment region.	24 month
Comparison of Seroconversion Proportions for HPV18, Assessed at 24 Months, by Enrollment District	HPV18 ELISA results at 24-months (interim analysis) by arm in the according to protocol analytical cohort stratified by enrollment region.	24 month

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: Cancer Research UK; Gates Foundation
• Investigators: Principal Investigator: Aimee R Kreimer, National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Cortes B, Ocampo R, Porras C, Liu D, Gail MH, Sierra MS, Herrero R, Lowy DR, Carvajal LJ, Kemp TJ, Fantin R, Schussler J, Hildesheim A, Sampson JN, Pinto LA, Schiller JT, Kreimer AR. Human papillomavirus (HPV) type 16 and type 18 antibody concentrations after a single dose of bivalent HPV vaccine in girls aged 9-14 years compared with three doses of quadrivalent HPV vaccine in women aged 18-25 years in Costa Rica (PRIMAVERA): a non-randomised, open-label, immunobridging, non-inferiority trial. Lancet Infect Dis. 2025 Jul 16:S1473-3099(25)00284-1. doi: 10.1016/S1473-3099(25)00284-1. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Actual): September 30, 2022
• Study Completion (Actual): April 23, 2024

Study Registration Dates

• First Submitted: November 1, 2018
• First Submitted That Met QC Criteria: November 1, 2018
• First Posted (Actual): November 2, 2018

Study Record Updates

• Last Update Posted (Actual): August 3, 2025
• Last Update Submitted That Met QC Criteria: July 21, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: HPV vaccine; Single dose HPV vaccination
• Additional Relevant MeSH Terms: Immunologic Factors; Physiological Effects of Drugs; Vaccines
• Other Study ID Numbers: NCI-2020-07432 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 19-C-N009 (Other Identifier: National Cancer Institute)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: There is a plan to make IPD and related data dictionaries available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No