Human Papillomavirus-Related Cervical CarcinomaPhase 3PRIMAVERANCT03728881

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

A Phase 3 study testing Quadrivalent Human Papillomavirus (types 6, 11, 16, 18) Recombinant Vaccine and Recombinant Human Papillomavirus Bivalent Vaccine in people with Human Papillomavirus-Related Cervical Carcinoma, run by National Cancer Institute (NCI) at 1 site in Costa Rica.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 9 to 25 years, women onlyHealthy volunteers can take part
Conditions the study is for: Human Papillomavirus-Related Cervical Carcinoma
What is being tested?: Quadrivalent Human Papillomavirus (types 6, 11, 16, 18) Recombinant Vaccine and Recombinant Human Papillomavirus Bivalent Vaccine
Type of treatment: Vaccines
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1,240 participants
Where: 1 siteCosta Rica
Study dates: 1 Apr 2019to 23 Apr 2024
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 9 to 25 years
Women only
Healthy volunteers accepted
Child, Adult

Who may be able to join

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

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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)

Who cannot join

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

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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

Trial locations and contacts

1 site in 1 country.

Costa Rica1 site

Agencia Costarricense de Investigaciones Biomédicas (ACIB)
Liberia, Guanacaste Province, 50101

Other trials in Costa Rica

About this study

Official title: 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.

Read the detailed description

PRIMARY OBJECTIVE:

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:

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.

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.

Conditions: Human Papillomavirus-Related Cervical Carcinoma
Being tested: Quadrivalent Human Papillomavirus (types 6, 11, 16, 18) Recombinant Vaccine, Recombinant Human Papillomavirus Bivalent Vaccine
Keywords: HPV vaccine, Single dose HPV vaccination

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Quadrivalent Human Papillomavirus (types 6, 11, 16, 18) Recombinant VaccineBiological
Also called Gardasil, 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
Given IM
Recombinant Human Papillomavirus Bivalent VaccineBiological
Also called Cervarix, GSK-580299, HPV 16/18 L1 VLP/AS04 VAC, HPV-16/18 VLP/AS04 Vaccine
Given IM

Study groups in NCT03728881
Study group	Role	What they receive
Girls (1D Cervarix®)	Experimental	Participants 9-14 years old receive Cervarix IM at baseline. Receives: Biological: Recombinant Human Papillomavirus Bivalent Vaccine
Women (3D Gardasil-4®)	Active comparator	Participants 18-25 years old receive Gardasil IM at baseline and at 2 and 6 months in the absence of unacceptable toxicity. Receives: Biological: Quadrivalent Human Papillomavirus (types 6, 11, 16, 18) Recombinant Vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 24 months following initial vaccination

Secondary outcomes (68)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 24 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Apr 201923 Apr 2024

First posted2 Nov 2018
Study start1 Apr 2019
Primary completion30 Sep 2022
Study completion23 Apr 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Human Papillomavirus-Related Cervical CarcinomaStudies of the same condition, open and under way.
More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Prevention
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 1,240 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03728881
Sponsor's protocol ID: NCI-2020-07432
Other IDs: NCI-2020-07432, 19-C-N009
Acronym: PRIMAVERA
Status last verified: Jul 2025
First submitted: 1 Nov 2018
Last updated: 3 Aug 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: There is a plan to make IPD and related data dictionaries available.

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 Dec;25(12):1314-1324. doi: 10.1016/S1473-3099(25)00284-1. Epub 2025 Jul 16.
PubMed 40683285

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
E7 T-cell Receptor (TCR) -T Cell Induction Therapy for Locoregionally Advanced HPV-associated Cancers
HPV-Associated Cervical Carcinoma, HPV-Related Carcinoma
RecruitingPhase 2
E7 TCR-T Cell Immunotherapy for Human Papillomavirus (HPV) Associated Cancers
Cervical Cancer, Throat Cancer
Active, not recruitingPhase 4
Single-Dose HPV Vaccination for the Prevention of Cervical Cancer in Young Adult Women in Costa Rica, The PRISMA ESCUDDO Trial
Human Papillomavirus-Related Cervical Carcinoma
Active, not recruitingPhase 1/2
A Vaccine (PDS0101) Alone or in Combination With Pembrolizumab for the Treatment of Locally Advanced Human Papillomavirus-Associated Oropharynx Cancer
Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Human Papillomavirus-Related Carcinoma
RecruitingPhase 2
De-Escalated Adjuvant and Definitive Radiation Therapy Informed by DART 2.0 ctHPV-DNA
Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8

All Human Papillomavirus-Related Cervical Carcinoma trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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")
ClinicalTrials.gov ID: NCT03728881
Acronym / sponsor ID: PRIMAVERA / NCI-2020-07432
Conditions: Human Papillomavirus-Related Cervical Carcinoma
Keywords: HPV vaccine, Single dose HPV vaccination
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,240 participants (actual)
Lead sponsor: National Cancer Institute (NCI)US National Institutes of Health
Collaborators: Cancer Research UK, Bill and Melinda Gates Foundation
Study start: 1 Apr 2019 (actual)
Primary completion: 30 Sep 2022 (actual)
Study completion: 23 Apr 2024 (actual)
First posted: 2 Nov 2018 (actual)
Results: Posted 20 Jul 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVE:

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:

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.

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 design

Primary purpose: Prevention
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Girls (1D Cervarix®)	Experimental	Biological: Recombinant Human Papillomavirus Bivalent VaccineParticipants 9-14 years old receive Cervarix IM at baseline.
Women (3D Gardasil-4®)	Active comparator	Biological: Quadrivalent Human Papillomavirus (types 6, 11, 16, 18) Recombinant VaccineParticipants 18-25 years old receive Gardasil IM at baseline and at 2 and 6 months in the absence of unacceptable toxicity.

Who may qualify

Ages: 9 to 25 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Child, Adult

Key inclusion criteria (12 listed)

Aged between:
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

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Quadrivalent Human Papillomavirus (types 6, 11, 16, 18) Recombinant VaccineAlso: Gardasil, 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 VaccineGiven IM	Biological	Women (3D Gardasil-4®)
Recombinant Human Papillomavirus Bivalent VaccineAlso: Cervarix, GSK-580299, HPV 16/18 L1 VLP/AS04 VAC, HPV-16/18 VLP/AS04 VaccineGiven IM	Biological	Girls (1D Cervarix®)

Primary outcome

Number Seropositive for HPV16 at 36 Months
Time frame: 36 months following initial HPV vaccination
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.
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
Time frame: 36 months following 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.
Number Seropositive for HPV18 at 36 Months
Time frame: 36 months following initial vaccination
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.
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
Time frame: 36 months following 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.
Number Seropositive for HPV16 at 24 Months
Time frame: 24 months following initial HPV vaccination
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.
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
Time frame: 24 months following 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
Number Seropositive for HPV18 at 24 Months
Time frame: 24 months following initial vaccination
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.
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
Time frame: 24 months following 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.

68 secondary outcomes

Comparison of Proportions With Seroconversion Based on HPV16 Antibody Levels Assessed at 36 Months
Time frame: 36 months
Comparison of Proportions With Seroconversion Based on HPV18 Antibody Levels Assessed at 36 Months
Time frame: 36 month
Comparison of Proportions With Seroconversion Based HPV16 Antibody Levels at 24 Months
Time frame: 24 months
Comparison of Proportions With Seroconversion Based on HPV18 Antibody Levels Assessed at 24 Months
Time frame: 24 months
Comparison of Distribution of HPV16 Antibodies Levels Assessed at 36 Months
Time frame: 36 months following initial vaccination
Comparison of Distribution of HPV18 Antibodies Levels Assessed at 36 Months
Time frame: 36 months
Comparison of Distribution of HPV16 Antibodies Levels Assessed at 24 Months
Time frame: 24 months
Comparison of Distribution of HPV18 Antibodies Levels Assessed at 24 Months
Time frame: 24 months
Number Seropositive for HPV16 at 36 Months, Excluding 9-10 Year Olds
Time frame: 36 month
Comparison of GMCs for HPV16 Antibodies Assessed at 36 Months, Excluding 9-10-year-old Girls
Time frame: 36 month
Comparison of Seroconversion Proportions for HPV16 Antibodies Assessed at 36 Months, Excluding 9-10-year-old Girls
Time frame: 36 month
Number Seropositive for HPV18 at 36 Months, Excluding 9-10 Year Olds
Time frame: 36 month
Comparison of GMCs for HPV18 Antibodies, Assessed at 36 Months, Excluding 9-10-year-old Girls
Time frame: 36 month
Comparison of Seroconversion Proportions for HPV18 Antibodies, Assessed at 36 Months, Excluding 9-10-year-old Girls
Time frame: 36 month
Number Seropositive for HPV16 at 24 Months, Excluding 9-10 Year Olds
Time frame: 24 month
Comparison of GMCs for HPV16 Assessed at 24 Months, Excluding 9-10-year-old Girls
Time frame: 24 months
Comparison of Seroconversion Proportions for HPV16 Assessed at 24 Months, Excluding 9-10-year-old Girls
Time frame: 24 months
Number Seropositive for HPV18 at 24 Months, Excluding 9-10 Year Olds
Time frame: 24 month
Comparison of GMCs for HPV18 Antibodies, Assessed at 24 Months, Excluding 9-10-year-old Girls
Time frame: 24 months
Comparison of Seroconversion Proportions for HPV18 Antibodies, Assessed at 24 Months, Excluding 9-10-year-old Girls
Time frame: 24 months
Number Seropositive for HPV16 Antibodies, Assessed at 1 Month After Vaccination, in Younger and Older Girls
Time frame: 1 month
Comparison of GMCs for HPV16 Antibodies, Assessed at 1 Month After Vaccination in Younger and Older Girls
Time frame: 1 month
Comparison of Seroconversion Proportions for HPV16 Antibodies, Assessed at 1 Month After Vaccination in Younger and Older Girls
Time frame: 1 month
Number Seropositive for HPV18 Antibodies, Assessed at 1 Month After Vaccination, in Younger and Older Girls
Time frame: 1 month
Comparison of GMCs for HPV18 Antibodies, Assessed at 1 Month After Vaccination in Younger and Older Girls
Time frame: 1 month
Comparison of Seroconversion Proportions for HPV18 Antibodies, Assessed at 1 Month After Vaccination in Younger and Older Girls
Time frame: 1 month
Number Seropositive for HPV16 Antibodies, Assessed at 12 Months After Vaccination, in Younger and Older Girls
Time frame: 12 months
Comparison of GMCs for HPV16 Antibodies, Assessed at 12 Months After Vaccination in Younger and Older Girls
Time frame: 1 year
Comparison of Seroconversion Proportions for HPV16 Antibodies, Assessed at 12 Months After Vaccination in Younger and Older Girls
Time frame: 1 year
Number Seropositive for HPV18 Antibodies, Assessed at 12 Months After Vaccination, in Younger and Older Girls
Time frame: 12 month
Comparison of GMCs for HPV18 Antibodies, Assessed at 12 Months After Vaccination in Younger and Older Girls
Time frame: 12 months
Comparison of Seroconversion Proportions for HPV18 Antibodies, Assessed at 12 Months After Vaccination, in Younger and Older Girls
Time frame: 1 year
Number Seropositive for HPV16 at 36 Months, By Enrollment Age Group
Time frame: 36 months
Comparison of GMCs for HPV16 Antibodies Assessed at 36 Months, by Enrollment Age Group
Time frame: 36 month
Comparison of Seroconversion Proportions for HPV16, Assessed at 36 Months, by Enrollment Age Group
Time frame: 36 month
Number Seropositive for HPV18 at 36 Months, By Enrollment Age Group
Time frame: 36 months
Comparison of GMCs for HPV18 Antibodies, Assessed at 36 Months, by Enrollment Age Group
Time frame: 36 month
Comparison of Seroconversion Proportions for HPV18, Assessed at 36 Months, by Enrollment Age Group
Time frame: 36 month
Number Seropositive for HPV16 at 24 Months, By Enrollment Age Group
Time frame: 36 months
Comparison of GMCs for HPV16 Antibodies Assessed at 24 Months, by Enrollment Age Group
Time frame: 24 month

Results and safety

Results posted to the registry on 20 Jul 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Girls (1D Cervarix®)	620	575
Women (3D Gardasil-4®)	620	545

Primary outcome: Number Seropositive for HPV16 at 36 Months

Time frame: 36 months following initial HPV vaccination. Count of participants. Unit: Participants

Measure	Girls (1D Cervarix®) n = 539	Women (3D Gardasil-4®) n = 366
Value	538	366

Population analysed: The primary cohort for the final analysis of HPV16 includes participants who received the appropriate number of vaccine doses within the specified windows, were initially seronegative for HPV16, underwent blood collection at the 36-month mark, and reported no additional HPV vaccinations outside the study before the 36-month blood collection, as confirmed by self-report or serologic testing for HPV6/HPV11.

Primary outcome: 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

Time frame: 36 months following initial vaccination. Geometric mean (95% Confidence Interval). Unit: International units (IU/mL)

Measure	Girls (1D Cervarix®) n = 538	Women (3D Gardasil-4®) n = 366
Value	21.4 (19.7 to 23.3)	42.9 (38.9 to 47.3)

Girls (1D Cervarix®) vs Women (3D Gardasil-4®): GMC Ratio: 0.5 (96% CI 0.44 to 0.57)

Primary outcome: Number Seropositive for HPV18 at 36 Months

Time frame: 36 months following initial vaccination. Count of participants. Unit: Participants

Measure	Girls (1D Cervarix®) n = 523	Women (3D Gardasil-4®) n = 373
Value	517	358

Population analysed: The primary cohort for the final analysis of HPV18 includes participants who received the appropriate number of vaccine doses within the specified windows, were initially seronegative for HPV18, underwent blood collection at the 36-month mark, and reported no additional HPV vaccinations outside the study before the 36-month blood collection, as confirmed by self-report or serologic testing for HPV6/HPV11.

Primary outcome: 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

Time frame: 36 months following initial vaccination. Geometric mean (95% Confidence Interval). Unit: International units (IU/mL)

Measure	Girls (1D Cervarix®) n = 517	Women (3D Gardasil-4®) n = 358
Value	8.0 (7.4 to 8.8)	7.2 (6.4 to 8.1)

Girls (1D Cervarix®) vs Women (3D Gardasil-4®): Ratio of the GMCs: 1.11 (96% CI 0.95 to 1.29)

Population analysed: Will measure HPV-18 specific serum antibody using the HPV type-specific ELISA on serum. Will estimate the two-sided 96% confidence intervals of the Geometric Mean Concentration (GMC) ratio for HPV-18 at 36 months.

68 secondary outcomes are reported in the full results.

Adverse events

Time frame: The time points and duration of assessment of adverse events differs for each participant according to their enrollment and exit dates. Systematic assessment of adverse events began the first vaccination date and ended 180 days after last vaccination date. Non-systematic assessment began 181 days after last vaccination and ends the date the participant exits the study. Some participants are not yet exited from the study; however, for these results, the end date is April 23, 2024.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Girls (1D Cervarix®) Systematic Collection Phase	2 of 620 (0.3%)	71 of 620 (11.5%)	0 of 620
Women (3D Gardasil-4®) Systematic Collection Phase	13 of 620 (2.1%)	166 of 620 (26.8%)	1 of 620
Girls (1D Cervarix®) Non-systematic Collection Phase	3 of 620 (0.5%)	62 of 620 (10%)	1 of 620
Women (3D Gardasil-4®) Non-systematic Collection Phase	34 of 620 (5.5%)	73 of 620 (11.8%)	0 of 620

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 40683285Cortes 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 Dec;25(12):1314-1324. doi: 10.1016/S1473-3099(25)00284-1. Epub 2025 Jul 16.
Individual participant dataSharing planned: Yes. There is a plan to make IPD and related data dictionaries available.

Related trials for Human Papillomavirus-Related Cervical Carcinoma

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Aimee R Kreimer principal investigator

National Cancer Institute (NCI)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Costa Rica. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number Seropositive for HPV16 at 36 Months (time frame: 36 months following initial HPV vaccination). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03728881, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2025.